Type 2 Diabetes MellitusPhase 3NCT00328627
Efficacy and Safety of Alogliptin Combined With Pioglitazone in Treating Subjects With Type 2 Diabetes Mellitus.
A Phase 3 study testing Alogliptin and Pioglitazone in people with Type 2 Diabetes Mellitus, run by Takeda at 90 sites in 19 countries.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of alogliptin, once daily (QD), taken in combination with pioglitazone in adults with type 2 diabetes mellitus. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Alogliptin and Pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,554 participants
- Where
- 90 sitesin 19 countries
- Study dates
- May 2006to Mar 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women with a historical diagnosis of type 2 diabetes mellitus who were treated with metformin greater than or equal to 1500 mg alone but were experiencing inadequate glycemic control.
- A stable dose of metformin of greater than or equal to 1500 mg or maximum tolerated dose.
- No treatment with antidiabetic agents other than metformin within the 2 months prior to Screening.
- A body mass index greater than or equal to 23 kg/m^2 and less than or equal to 45 kg/m^2.
- Fasting C-peptide greater than or equal to 0.8 ng/mL.
- Regular use of other, non-excluded medications was allowed if a stable dose had been established for at least 4 weeks prior to Screening.
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- Systolic blood pressure less than or equal to 160 mmHg and diastolic pressure less than or equal to 100 mmHg.
- Hemoglobin greater than or equal to 12 g/dL for men and greater than or equal to 10 g/dL for women.
- Alanine aminotransferase less than or equal to 2.5 times the upper limit of normal.
- Serum creatinine less than 1.5 mg/dL for men and less than 1.4 mg/dL for women.
- Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject was clinically euthyroid.
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
- Able and willing to monitor their own blood glucose concentrations with a home glucose monitor.
- No major illness or debility that in the investigator's opinion prohibited the patient from completing the study.
Who cannot join
- Urine albumin/creatinine ratio greater than 113 mg/mmol at Screening.
- A history of cancer, other than squamous cell or basal cell carcinoma of the skin, that had not been in full remission for at least 5 years prior to Screening.
- A history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
- A history of treated diabetic gastroparesis.
- New York Heart Association Class III or IV heart failure regardless of therapy.
- History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening.
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- History of any hemoglobinopathy.
- History of infection with hepatitis B, hepatitis C or human immunodeficiency virus.
- History of a psychiatric disorder that could have affected the patient's ability to participate in the study.
- History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.
- A history of alcohol or substance abuse within 2 years prior to Screening.
- Receipt of any investigational drug within 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within 3 months prior to Screening.
- Previous participation in an investigational study of alogliptin.
- Hypersensitive to pioglitazone, alogliptin, or other excipients.
Trial locations and contacts
90 sites in 19 countries.
90 sites in 19 countries
United States72 sites
Study site
Alcoa, Tennessee
Study site
Allentown, Pennsylvania
Study site
Altoona, Pennsylvania
Study site
Ann Arbor, Michigan
Study site
Arlington, Texas
Study site
Atlanta, Georgia
Study site
Baton Rouge, Louisiana
Study site
Birmingham, Alabama
Study site
Blackwood, New Jersey
Study site
Burbank, California
Study site
Burlington, Vermont
Study site
Cadillac, Michigan
Study site
Carrollton, Texas
Study site
Charlotte, North Carolina
Study site
Chicago, Illinois
Study site
Clinton, Oklahoma
Study site
Colorado Springs, Colorado
Study site
Columbiana, Alabama
Study site
Dallas, Texas
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Detroit, Michigan
Study site
Elkridge, Maryland
Study site
Foothill Ranch, California
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Fort Worth, Texas
Study site
Gallipolis, Ohio
Study site
Hollywood, Florida
Study site
Houston, Texas
Study site
Huntsville, Alabama
Study site
Irvine, California
Study site
Kansas City, Missouri
Study site
Kissimmee, Florida
Study site
Lafayette, Indiana
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Little Rock, Arkansas
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Livonia, Michigan
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Marion, Ohio
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Marlborough, Massachusetts
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Marrero, Louisiana
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Miami, Florida
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Milan, Tennessee
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Morristown, Tennessee
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Munfordville, Kentucky
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New Port Richey, Florida
Study site
New York, New York
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North Las Vegas, Nevada
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Oklahoma City, Oklahoma
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Pembroke Pines, Florida
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Peoria, Illinois
Study site
Philadelphia, Pennsylvania
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Phoenix, Arizona
Study site
Pinellas Park, Florida
Study site
Pittsburgh, Pennsylvania
Study site
Prince Frederick, Maryland
Study site
Roswell, Georgia
Study site
Sacramento, California
Study site
Salt Lake City, Utah
Study site
San Antonio, Texas
Study site
San Diego, California
Study site
Sarasota, Florida
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Savannah, Georgia
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Searcy, Arkansas
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Sherwood, Arkansas
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South Bend, Indiana
Study site
Statesville, North Carolina
Study site
Temecula, California
Study site
Temple, Texas
Study site
Towson, Maryland
Study site
Trenton, New Jersey
Study site
Tulsa, Oklahoma
Study site
Tustin, California
Study site
Vero Beach, Florida
Study site
Warner Robins, Georgia
Study site
Washington D.C., District of Columbia
Study site
Waterloo, Iowa
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of the Combination of SYR-322 (SYR110322) and Pioglitazone HCl (ACTOS®), in Subjects With Type 2 Diabetes
The purpose of this study is to evaluate the safety and efficacy of alogliptin, once daily (QD), taken in combination with pioglitazone in adults with type 2 diabetes mellitus.
Read the detailed description
Over the past 30 years, the prevalence of diabetes has increased dramatically throughout the world due to population growth, aging, urbanization, increasing obesity, and physical inactivity. The total number of people with type 2 diabetes mellitus is projected to rise from 171 million in 2000 to 366 million in 2030. The incidence of type 2 diabetes mellitus in the United States alone is expected to increase from approximately 17 to 30.3 million by the year 2030. Type 2 diabetes mellitus is associated with a number of long-term microvascular and macrovascular complications associated with a reduced quality of life and increased morbidity and mortality. It is anticipated that the increasing incidence of type 2 diabetes mellitus will place an ever-increasing burden on families, increase national expenditures for health care services, and decrease worker productivity.
Current pharmacologic interventions for type 2 diabetes mellitus include a diverse range of antidiabetic medications with different mechanisms of action including insulin and insulin analogues, sulfonylureas, metformin, meglitinides, thiazolidinediones, inhibitors of alpha-glucosidase, analogs of glucagon-like peptide-1 and synthetic analogues of human amylin. Despite the variety of medications, many have clinically important or potentially life-threatening side effects, restricted use in many subpopulations, concerns with long-term tolerability, and challenges related to compliance due to side effects and route of administration. All of these reasons contribute to the difficulties patients have achieving the target glycosylated hemoglobin level less than 7%.
SYR-322 (alogliptin) is a selective, orally available inhibitor of the dipeptidyl peptidase-4 enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus.
Pioglitazone (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan) that is approved for the treatment of type 2 diabetes mellitus. Pioglitazone is a selective peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in the periphery and liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
Given the complementary mechanisms of action of alogliptin (stimulation of insulin secretion) and pioglitazone (enhancement of insulin sensitivity), the goal of this study is to evaluate the efficacy of the combination of alogliptin with pioglitazone in patients who are inadequately controlled on metformin. Study participation is anticipated to be approximately 7 months.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Alogliptin, Alogliptin placebo, Pioglitazone, Pioglitazone placebo
- Keywords
- Diabetes Mellitus, Type 2, Drug Therapy, Diabetes Mellitus, Non Insulin Dependent, Glucose Intolerance, Hyperglycemia
- Medical subject headings
- Diabetes Mellitus, Type 2, Glucose Intolerance, Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlogliptinDrug
Also called SYR-322
Alogliptin tablets.
Alogliptin placeboDrug
Alogliptin placebo-matching tablets.
PioglitazoneDrug
Also called ACTOS®
Pioglitazone tablets.
Pioglitazone placeboDrug
Pioglitazone placebo-matching tablets.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin placebo; Drug: Pioglitazone placebo |
| Alogliptin 12.5 + Placebo | Experimental | Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin; Drug: Pioglitazone placebo |
| Alogliptin 25 + Placebo | Experimental | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin; Drug: Pioglitazone placebo |
| Placebo + Pioglitazone 15 | Active comparator | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. Receives: Drug: Pioglitazone |
| Alogliptin 12.5 + Pioglitazone 15 | Experimental | Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin; Drug: Pioglitazone |
| Alogliptin 25 + Pioglitazone 15 | Experimental | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin; Drug: Pioglitazone |
| Placebo + Pioglitazone 30 | Active comparator | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin placebo; Drug: Pioglitazone |
| Alogliptin 12.5 + Pioglitazone 30 | Experimental | Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin; Drug: Pioglitazone |
| Alogliptin 25 + Pioglitazone 30 | Experimental | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin; Drug: Pioglitazone |
| Placebo + Pioglitazone 45 | Active comparator | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin placebo; Drug: Pioglitazone |
| Alogliptin 12.5 + Pioglitazone 45 | Experimental | Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin; Drug: Pioglitazone |
| Alogliptin 25 + Pioglitazone 45 | Experimental | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. Receives: Drug: Alogliptin; Drug: Pioglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis)
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone).
Measured: Baseline and Week 26
Change From Baseline to Week 26 in HbA1c
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
Measured: Baseline and Week 26
Secondary outcomes (154)
Change From Baseline in HbA1c Over Time (Grouped Analysis)
The change from Baseline to Weeks 4, 8, 12, 16 and 20 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as class variables, and baseline metformin dose and HbA1c as continuous covariates.
Measured: Baseline and Weeks 4, 8, 12, 16 and 20.
Change From Baseline to Week 4 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 4. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 8. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 12.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 16. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 20.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis)
The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Measured: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 1 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Measured: Baseline and Week 1
Change From Baseline to Week 2 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Measured: Baseline and Week 2
Change From Baseline to Week 4 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Measured: Baseline and Week 26
Percentage of Participants With Marked Hyperglycemia (Grouped Analysis)
Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Measured: From Week 1 to Week 26
Percentage of Participants With Marked Hyperglycemia
Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).
Measured: From Week 1 to Week 26
Percentage of Participants Meeting Rescue Criteria (Grouped Analysis)
Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory:
- After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL;
- From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL;
- From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL;
- From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Measured: From Week 1 to Week 26.
Percentage of Participants Meeting Rescue Criteria
Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory:
- After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL;
- From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL;
- From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL;
- From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Measured: From Week 1 to Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Measured: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5%
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.
Measured: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Measured: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 7%
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%.
Measured: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Measured: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5%
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.
Measured: Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Measured: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.
Measured: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Measured: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%.
Measured: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Measured: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.
Measured: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Measured: Baseline and Week 26.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2%.
Measured: Baseline and Week 26
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis)
Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and proinsulin as continuous covariates.
Measured: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 4 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Insulin Over Time (Grouped Analysis)
The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Measured: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 4 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis)
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20 and 26 relative to the Baseline value.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Measured: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 4 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in C-peptide Over Time (Grouped Analysis)
C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Measured: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 4 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Total Cholesterol Over Time (Grouped Analysis)
Change from Baseline in total cholesterol was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Measured: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 4 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis)
Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Measured: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis)
Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Measured: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Triglycerides Over Time (Grouped Analysis)
Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Measured: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 4 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Measured: Baseline and Week 4
Change From Baseline to Week 8 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 16 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Measured: Baseline and Week 16
Change From Baseline to Week 20 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis)
Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Measured: Baseline and Weeks 12 and 26.
Change From Baseline to Week 12 in Free Fatty Acids
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Free Fatty Acids
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis)
Change from Baseline in plasminogen activator inhibitor-1 (PAI-1) was assessed at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Measured: Baseline and Weeks 12 and 26.
Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis)
Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Measured: Baseline and Weeks 12 and 26.
Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Adiponectin Over Time (Grouped Analysis)
Change from Baseline in adiponectin was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Measured: Baseline and Weeks 12 and 26.
Change From Baseline to Week 12 in Adiponectin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Adiponectin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Body Weight Over Time (Grouped Analysis)
Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Measured: Baseline and Weeks 8, 12, 20 and 26.
Change From Baseline to Week 8 in Body Weight
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Measured: Baseline and Week 8
Change From Baseline to Week 12 in Body Weight
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 20 in Body Weight
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Measured: Baseline and Week 20
Change From Baseline to Week 26 in Body Weight
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis)
HOMA IR measures insulin resistance based on fasting glucose and insulin measurements:
HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5.
A higher number indicates a greater insulin resistance. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Measured: Baseline and Weeks 12 and 26.
Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance
The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements:
HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5.
A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance
The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements:
HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5.
A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis)
The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B).
HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function
The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population.
HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function
The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population.
HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis)
Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Measured: Baseline and Weeks 12 and 26.
Change From Baseline to Week 12 in Apolipoprotein A1
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Apolipoprotein A1
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis)
Change from Baseline in Apolipoprotein A2 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in Apolipoprotein A2
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Apolipoprotein A2
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis)
Change from Baseline in Apolipoprotein B was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in Apolipoprotein B
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Apolipoprotein B
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis)
Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in Apolipoprotein C-III
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Apolipoprotein C-III
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis)
Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Measured: Baseline and Weeks 12 and 26.
Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides
NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 12.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides
NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 26.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis)
The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in VLDL / Chylomicron Particles
The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in VLDL / Chylomicron Particles
The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis)
The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides
The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides
The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in VLDL Particles Over Time (Grouped Analysis)
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in VLDL Particles
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in VLDL Particles
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates
Measured: Baseline and Week 26
Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis)
The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in Mean VLDL Particle Size
The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Mean VLDL Particle Size
The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis)
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in IDL Particles
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in IDL Particles
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis)
The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR fractionation at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in LDL Particles
The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in LDL Particles
The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis)
The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in Mean LDL Particle Size
The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Mean LDL Particle Size
The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis)
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Measured: Baseline and Weeks 12 and 26.
Change From Baseline to Week 12 in HDL Particles
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in HDL Particles
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation.
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Measured: Baseline and Week 26
Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis)
The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26.
This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Measured: Baseline and Weeks 12 and 26
Change From Baseline to Week 12 in Mean HDL Particle Size
The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Measured: Baseline and Week 12
Change From Baseline to Week 26 in Mean HDL Particle Size
The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Measured: Baseline and Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2006 (estimated)
- Study startMay 2006
- Primary completionMar 2008
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,554 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- VP Biological Sciences, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00328627
- Sponsor's protocol ID
- 01-05-TL-322OPI-001
- Other IDs
- 2006-000694-30, U1111-1113-8587
- Status last verified
- Feb 2013
- First submitted
- 19 May 2006
- Last updated
- 4 Apr 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
DeFronzo RA, Burant CF, Fleck P, Wilson C, Mekki Q, Pratley RE. Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes. J Clin Endocrinol Metab. 2012 May;97(5):1615-22. doi: 10.1210/jc.2011-2243. Epub 2012 Mar 14.
PubMed 22419732
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of the Combination of SYR-322 (SYR110322) and Pioglitazone HCl (ACTOS®), in Subjects With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT00328627
- Acronym / sponsor ID
- 01-05-TL-322OPI-001
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Diabetes Mellitus, Type 2, Drug Therapy, Diabetes Mellitus, Non Insulin Dependent, Glucose Intolerance, Hyperglycemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,554 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 22 May 2006 (estimated)
- Results
- Posted 4 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and efficacy of alogliptin, once daily (QD), taken in combination with pioglitazone in adults with type 2 diabetes mellitus.
Detailed description
Over the past 30 years, the prevalence of diabetes has increased dramatically throughout the world due to population growth, aging, urbanization, increasing obesity, and physical inactivity. The total number of people with type 2 diabetes mellitus is projected to rise from 171 million in 2000 to 366 million in 2030. The incidence of type 2 diabetes mellitus in the United States alone is expected to increase from approximately 17 to 30.3 million by the year 2030. Type 2 diabetes mellitus is associated with a number of long-term microvascular and macrovascular complications associated with a reduced quality of life and increased morbidity and mortality. It is anticipated that the increasing incidence of type 2 diabetes mellitus will place an ever-increasing burden on families, increase national expenditures for health care services, and decrease worker productivity.
Current pharmacologic interventions for type 2 diabetes mellitus include a diverse range of antidiabetic medications with different mechanisms of action including insulin and insulin analogues, sulfonylureas, metformin, meglitinides, thiazolidinediones, inhibitors of alpha-glucosidase, analogs of glucagon-like peptide-1 and synthetic analogues of human amylin. Despite the variety of medications, many have clinically important or potentially life-threatening side effects, restricted use in many subpopulations, concerns with long-term tolerability, and challenges related to compliance due to side effects and route of administration. All of these reasons contribute to the difficulties patients have achieving the target glycosylated hemoglobin level less than 7%.
SYR-322 (alogliptin) is a selective, orally available inhibitor of the dipeptidyl peptidase-4 enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus.
Pioglitazone (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan) that is approved for the treatment of type 2 diabetes mellitus. Pioglitazone is a selective peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in the periphery and liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
Given the complementary mechanisms of action of alogliptin (stimulation of insulin secretion) and pioglitazone (enhancement of insulin sensitivity), the goal of this study is to evaluate the efficacy of the combination of alogliptin with pioglitazone in patients who are inadequately controlled on metformin. Study participation is anticipated to be approximately 7 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Alogliptin placebo, Drug: Pioglitazone placeboAlogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. |
| Alogliptin 12.5 + Placebo | Experimental | Drug: Alogliptin, Drug: Pioglitazone placeboAlogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. |
| Alogliptin 25 + Placebo | Experimental | Drug: Alogliptin, Drug: Pioglitazone placeboAlogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. |
| Placebo + Pioglitazone 15 | Active comparator | Drug: PioglitazoneAlogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. |
| Alogliptin 12.5 + Pioglitazone 15 | Experimental | Drug: Alogliptin, Drug: PioglitazoneAlogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. |
| Alogliptin 25 + Pioglitazone 15 | Experimental | Drug: Alogliptin, Drug: PioglitazoneAlogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. |
| Placebo + Pioglitazone 30 | Active comparator | Drug: Alogliptin placebo, Drug: PioglitazoneAlogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. |
| Alogliptin 12.5 + Pioglitazone 30 | Experimental | Drug: Alogliptin, Drug: PioglitazoneAlogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. |
| Alogliptin 25 + Pioglitazone 30 | Experimental | Drug: Alogliptin, Drug: PioglitazoneAlogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. |
| Placebo + Pioglitazone 45 | Active comparator | Drug: Alogliptin placebo, Drug: PioglitazoneAlogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. |
| Alogliptin 12.5 + Pioglitazone 45 | Experimental | Drug: Alogliptin, Drug: PioglitazoneAlogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. |
| Alogliptin 25 + Pioglitazone 45 | Experimental | Drug: Alogliptin, Drug: PioglitazoneAlogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Men or women with a historical diagnosis of type 2 diabetes mellitus who were treated with metformin greater than or equal to 1500 mg alone but were experiencing inadequate glycemic control.
- A stable dose of metformin of greater than or equal to 1500 mg or maximum tolerated dose.
- No treatment with antidiabetic agents other than metformin within the 2 months prior to Screening.
- A body mass index greater than or equal to 23 kg/m^2 and less than or equal to 45 kg/m^2.
- Fasting C-peptide greater than or equal to 0.8 ng/mL.
Key exclusion criteria (14 listed)
- Urine albumin/creatinine ratio greater than 113 mg/mmol at Screening.
- A history of cancer, other than squamous cell or basal cell carcinoma of the skin, that had not been in full remission for at least 5 years prior to Screening.
- A history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
- A history of treated diabetic gastroparesis.
- New York Heart Association Class III or IV heart failure regardless of therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlogliptinAlso: SYR-322Alogliptin tablets. | Drug | Alogliptin 12.5 + Pioglitazone 15, Alogliptin 12.5 + Pioglitazone 30, Alogliptin 12.5 + Pioglitazone 45, Alogliptin 12.5 + Placebo, Alogliptin 25 + Pioglitazone 15, Alogliptin 25 + Pioglitazone 30, Alogliptin 25 + Pioglitazone 45, Alogliptin 25 + Placebo |
| Alogliptin placeboAlogliptin placebo-matching tablets. | Drug | Placebo, Placebo + Pioglitazone 30, Placebo + Pioglitazone 45 |
| PioglitazoneAlso: ACTOS®Pioglitazone tablets. | Drug | Alogliptin 12.5 + Pioglitazone 15, Alogliptin 12.5 + Pioglitazone 30, Alogliptin 12.5 + Pioglitazone 45, Alogliptin 25 + Pioglitazone 15, Alogliptin 25 + Pioglitazone 30, Alogliptin 25 + Pioglitazone 45, Placebo + Pioglitazone 15, Placebo + Pioglitazone 30, Placebo + Pioglitazone 45 |
| Pioglitazone placeboPioglitazone placebo-matching tablets. | Drug | Alogliptin 12.5 + Placebo, Alogliptin 25 + Placebo, Placebo |
Primary outcome
Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis)
Time frame: Baseline and Week 26
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone).
Change From Baseline to Week 26 in HbA1c
Time frame: Baseline and Week 26
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
154 secondary outcomes
Change From Baseline in HbA1c Over Time (Grouped Analysis)
Time frame: Baseline and Weeks 4, 8, 12, 16 and 20.
Change From Baseline to Week 4 in HbA1c
Time frame: Baseline and Week 4
Change From Baseline to Week 8 in HbA1c
Time frame: Baseline and Week 8
Change From Baseline to Week 12 in HbA1c
Time frame: Baseline and Week 12
Change From Baseline to Week 16 in HbA1c
Time frame: Baseline and Week 16
Change From Baseline to Week 20 in HbA1c
Time frame: Baseline and Week 20
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis)
Time frame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 1 in Fasting Plasma Glucose
Time frame: Baseline and Week 1
Change From Baseline to Week 2 in Fasting Plasma Glucose
Time frame: Baseline and Week 2
Change From Baseline to Week 4 in Fasting Plasma Glucose
Time frame: Baseline and Week 4
Change From Baseline to Week 8 in Fasting Plasma Glucose
Time frame: Baseline and Week 8
Change From Baseline to Week 12 in Fasting Plasma Glucose
Time frame: Baseline and Week 12
Change From Baseline to Week 16 in Fasting Plasma Glucose
Time frame: Baseline and Week 16
Change From Baseline to Week 20 in Fasting Plasma Glucose
Time frame: Baseline and Week 20
Change From Baseline to Week 26 in Fasting Plasma Glucose
Time frame: Baseline and Week 26
Percentage of Participants With Marked Hyperglycemia (Grouped Analysis)
Time frame: From Week 1 to Week 26
Percentage of Participants With Marked Hyperglycemia
Time frame: From Week 1 to Week 26
Percentage of Participants Meeting Rescue Criteria (Grouped Analysis)
Time frame: From Week 1 to Week 26.
Percentage of Participants Meeting Rescue Criteria
Time frame: From Week 1 to Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis)
Time frame: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5%
Time frame: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis)
Time frame: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 7%
Time frame: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis)
Time frame: Week 26
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5%
Time frame: Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis)
Time frame: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5%
Time frame: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis)
Time frame: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1%
Time frame: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis)
Time frame: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5%
Time frame: Baseline and Week 26
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis)
Time frame: Baseline and Week 26.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2%
Time frame: Baseline and Week 26
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis)
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Change From Baseline to Week 4 in Fasting Proinsulin
Time frame: Baseline and Week 4
Change From Baseline to Week 8 in Fasting Proinsulin
Time frame: Baseline and Week 8
Change From Baseline to Week 12 in Fasting Proinsulin
Time frame: Baseline and Week 12
Change From Baseline to Week 16 in Fasting Proinsulin
Time frame: Baseline and Week 16
Change From Baseline to Week 20 in Fasting Proinsulin
Time frame: Baseline and Week 20
Change From Baseline to Week 26 in Fasting Proinsulin
Time frame: Baseline and Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22419732DeFronzo RA, Burant CF, Fleck P, Wilson C, Mekki Q, Pratley RE. Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes. J Clin Endocrinol Metab. 2012 May;97(5):1615-22. doi: 10.1210/jc.2011-2243. Epub 2012 Mar 14.
- ACTOS® Package InsertLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
VP Biological Sciences study director
Takeda
90 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alogliptin and Pioglitazone in people with Type 2 Diabetes Mellitus, run by Takeda at 90 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 90 sites in United States, Australia, Brazil, Bulgaria, Chile and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis) (time frame: Baseline and Week 26). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00328627, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2013.