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Diabetes MellitusPhase 2NCT00760344

Efficacy and Safety of SYR-472 in Subjects With Type 2 Diabetes Mellitus

A Phase 2 study testing SYR-472 and Sitagliptin in people with Diabetes Mellitus, run by Takeda at 112 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to determine the efficacy and safety of SYR-472, once daily (QD), in subjects with type 2 diabetes mellitus who have not achieved glycemic control with diet and exercise, or by taking metformin. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Diabetes Mellitus
What is being tested?
SYR-472 and Sitagliptin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
386 participants
Where
112 sitesin 2 countries
Study dates
Mar 2007to Mar 2008
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Had a historical diagnosis of type 2 diabetes mellitus.
  • Had undergone less than 7 days of any antidiabetic therapy except lifestyle modification (diet/exercise) within 8 weeks prior to Screening; or has received metformin monotherapy for at least 8 weeks prior to Screening and maintained a stable daily dose of metformin for at least 12 weeks prior to randomization.
  • If receiving metformin monotherapy at randomization must have been at least 75% compliant with his or her regimen during the Run in/Stabilization Period as determined by subject diary and investigator assessment.
  • Had received no treatment with antidiabetic agents other than metformin within the 8 weeks prior to Screening.
  • The subject has an glycosylated hemoglobin concentration between 7.0% and 10.0%, inclusive, at Screening and at the Week -1 Visit.
  • Had a body mass index between 23 and 45 kg/m2.
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  • A C-peptide concentration is greater than or equal to 0.8 ng/mL (greater than or equal to 0.26 nmol/L).
  • A fasting plasma glucose concentration is less than 275 mg/dL (less than 15.27 mmol/L) at Screening and at the Week -1 Visit.
  • If the subject regularly uses other non-excluded medications, he or she must be on a stable dose for at least the 4 weeks prior to Screening.
  • The subject has a systolic blood pressure reading of less than 160 mm Hg and a diastolic pressure reading of less than 100 mm Hg.
  • The subject has a hemoglobin value greater than or equal to 12 g/dL (greater than or equal to 120 g/L) for men and greater than or equal to 10 g/dL (greater than or equal to 100 g/L) for women.
  • Had an alanine aminotransferase level is less than or equal to 3 times the upper limit of normal.
  • A male subject has a serum creatinine value of less than 1.5 mg/dL (less than 133 μmol/L); a female subject has a serum creatinine value of less than 1.4 mg/dL (less than 124 μmol/L).
  • Had a urine albumin/creatinine ratio of less than 1000 μg/mg at Screening.
  • Had a thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject is clinically euthyroid.
  • A female subject of childbearing potential who is sexually active must agree to use adequate contraception, and must be neither pregnant nor lactating from Screening and throughout the duration of the study.
  • Was able and willing to monitor his or her own blood glucose concentrations with a home glucose monitor.
  • Had no major illness or debility that in the investigator's opinion prohibits the subject from completing the study.

Who cannot join

  • Was being concurrently treated with antidiabetic therapy other than metformin and lifestyle intervention.
  • Had a history of cancer, other than squamous cell or basal cell carcinoma of the skin that has not been in full remission for at least 5 years prior to Screening.
  • Had a history of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
  • Had a history of treated diabetic gastric paresis.
  • Had a New York Heart Association class III or IV heart failure regardless of therapy.
  • Had a history of coronary angioplasty, coronary stent placement or coronary bypass surgery, myocardial infarction, or stroke within the 6 months prior to Screening.
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  • Had a history of hemoglobinopathy that may affect determination of glycosylated hemoglobin.
  • Had a history of infection with human immunodeficiency virus.
  • Had a history of a psychiatric disorder that in the investigator's opinion will affect the subject's ability to participate in the study.
  • Had a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) or substance abuse (defined as illicit drug use) within the 2 years prior to Screening.
  • Was required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
  • Ingested or received systemically injected glucocorticoids within the 3 months prior to randomization.
  • Used prescription or over-the-counter weight-loss drugs within the 3 months prior to randomization.
  • Received any investigational drug within the 30 days prior to Screening or has received an investigational antidiabetic drug within the 3 months prior to Screening.
  • Had received previous treatment in an investigational study of SYR-472.
  • Had a known hypersensitivity to any compound related to SYR-472 or Sitagliptin.

Trial locations and contacts

112 sites in 2 countries.

112 sites in 2 countries

United States105 sites

  • Study site

    Albuquerque, New Mexico

  • Study site

    Anderson, Arkansas

  • Study site

    Arvada, Colorado

  • Study site

    Atlanta, Georgia

  • Study site

    Aventura, Florida

  • Study site

    Avon, Connecticut

  • Study site

    Avon, Indiana

  • Study site

    Bensalem, Pennsylvania

  • Study site

    Birmingham, Alabama

  • Study site

    Bismarck, North Dakota

  • Study site

    Carmichael, California

  • Study site

    Carrolton, Texas

  • Study site

    Charleston, South Carolina

  • Study site

    Chattanooga, Tennessee

  • Study site

    Chicago, Illinois

  • Study site

    Chino, California

  • Study site

    Cincinnati, Ohio

  • Study site

    Colorado Springs, Colorado

  • Study site

    Columbus, Ohio

  • Study site

    Connellsville, Pennsylvania

  • Study site

    Crestview, Kentucky

  • Study site

    Dallas, Texas

  • Study site

    Des Moines, Iowa

  • Study site

    Detroit, Michigan

  • Study site

    East Islip, New York

  • Study site

    Edgewater, Florida

  • Study site

    Eugene, Oregon

  • Study site

    Fort Wayne, Indiana

  • Study site

    Georgetown, Texas

  • Study site

    Greer, South Carolina

  • Study site

    Hickory, North Carolina

  • Study site

    Highlands Ranch, Colorado

  • Study site

    Hollywood, Florida

  • Study site

    Houston, Texas

  • Study site

    Idaho Falls, Idaho

  • Study site

    Jacksonville, Florida

  • Study site

    Kansas City, Missouri

  • Study site

    Killeen, Texas

  • Study site

    Kissimmee, Florida

  • Study site

    Las Vegas, Nevada

  • Study site

    Lewiston, New York

  • Study site

    Little Rock, Arkansas

  • Study site

    Long Beach, California

  • Study site

    Los Angeles, California

  • Study site

    Los Gatos, California

  • Study site

    Mason, Ohio

  • Study site

    Medford, Oregon

  • Study site

    Memphis, Tennessee

  • Study site

    Merritt Island, Florida

  • Study site

    Miami, Florida

  • Study site

    Mobile, Alabama

  • Study site

    Montgomery, Alabama

  • Study site

    New Port Richey, Florida

  • Study site

    New Tazewell, Tennessee

  • Study site

    New York, New York

  • Study site

    Newark, Delaware

  • Study site

    Norman, Oklahoma

  • Study site

    North Massapequa, New York

  • Study site

    North Myrtle Beach, South Carolina

  • Study site

    Ocala, Florida

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Olive Branch, Mississippi

  • Study site

    Omaha, Nebraska

  • Study site

    Orange, California

  • Study site

    Oxon Hill, Maryland

  • Study site

    Pembroke Pines, Florida

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Phoenix, Arizona

  • Study site

    Pico Rivera, California

  • Study site

    Pine Bluff, Arkansas

  • Study site

    Pittsburgh, Pennsylvania

  • Study site

    Richmond, Virginia

  • Study site

    Rocky Hill, Connecticut

  • Study site

    Rolling Hills Estates, California

  • Study site

    Roseville, California

  • Study site

    Roswell, Georgia

  • Study site

    Rowland Heights, California

  • Study site

    Sacramento, California

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    Santa Ana, California

  • Study site

    Shippensburg, Pennsylvania

  • Study site

    Spanish Fork, Utah

  • Study site

    Spokane, Washington

  • Study site

    St Louis, Missouri

  • Study site

    Statesville, North Carolina

  • Study site

    Stockton, California

  • Study site

    Suffolk, Virginia

  • Study site

    Tabor City, North Carolina

  • Study site

    Tampa, Florida

  • Study site

    Tempe, Arizona

  • Study site

    Topeka, Kansas

  • Study site

    Torrance, California

  • Study site

    Troy, Michigan

  • Study site

    Tucson, Arizona

  • Study site

    Tulsa, Oklahoma

  • Study site

    Virginia Beach, Virginia

  • Study site

    Wadsworth, Ohio

  • Study site

    Wantagh, New York

  • Study site

    Waterloo, Iowa

  • Study site

    Waycross, Georgia

  • Study site

    West Caldwell, New Jersey

  • Study site

    Wichita, Kansas

  • Study site

    Wildwood Crest, New Jersey

  • Study site

    Zanesville, Florida

Other trials in United States

Mexico7 sites

  • Study site

    Mexico City

  • Study site

    Monterrey, Nuevo León

  • Study site

    Monterrey

  • Study site

    Nezahualcóyotl

  • Study site

    Puebla City, Puebla

  • Study site

    Veracruz

  • Study site

    Zapopan, Jalisco

Other trials in Mexico

About this study

Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate Treatment With SYR-472 in Subjects With Type 2 Diabetes

The purpose of this study is to determine the efficacy and safety of SYR-472, once daily (QD), in subjects with type 2 diabetes mellitus who have not achieved glycemic control with diet and exercise, or by taking metformin.

Read the detailed description

Type 2 diabetes mellitus is a complex metabolic disorder characterized by abnormal insulin secretion and glucose homeostasis, resulting from impaired pancreatic beta-cell function and insulin resistance in target tissues. The worldwide prevalence of type 2 diabetes mellitus is reaching epidemic proportions, and the total number of cases is expected to reach 221 million by 2010. The high incidence of the disease and its associated complications places a significant burden on healthcare systems.

The primary risk factor for the development of type 2 diabetes mellitus is obesity and its associated insulin resistance. Insulin resistance is characterized by an impaired response to the physiologic effects of insulin and leads to decreased cellular glucose uptake, increased hepatic gluconeogenesis, and a compensatory increase in insulin secretion that contributes to beta-cell exhaustion. Therefore in the insulin-resistant state, blood glucose and insulin levels are increased. The relationship between improved glycemic control in patients with type 2 diabetes mellitus and the delay or prevention of comorbidities has been reported in the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study. Therefore, reduction of persistent hyperglycemia is the highest priority in treating this disease.

Diet and exercise are important and effective measures for maintaining glycemic control in individuals with insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus, particularly in the early stages of disease progression. In cases where diet and exercise alone fail to adequately maintain glycemic control, oral antidiabetic drugs are typically used. Combination oral therapy and eventually insulin are usually required to maintain lower blood glucose levels but can result in adverse effects including hypoglycemia and weight gain. Therefore, novel safe and effective antidiabetic therapies are needed.

Dipeptidyl peptidase-4 is a ubiquitous aminopeptidase that is widely expressed in many tissues; it is thought to be primarily responsible for the in vivo degradation of at least two gut-derived incretin hormones, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are both released in response to nutrient ingestion. Glucagon-like peptide-1 has been demonstrated to augment glucose-dependent insulin secretion; suppress glucagon release and hepatic gluconeogenesis; inhibit gastric emptying, and reduce appetite and food intake. Glucagon-like peptide-1 and glucose-dependent insulinotropic peptide also have been shown to promote insulin biosynthesis and stimulate beta cell proliferation and survival. Orally available inhibitors of dipeptidyl peptidase-4 activity have been developed that increase intact postprandial glucagon-like peptide-1 levels after oral administration.

SYR-472 is a selective inhibitor of dipeptidyl peptidase-4 in development to improve glycemic control in patients with type 2 diabetes mellitus. The aim of this study is to evaluate SYR-472 in subjects with type 2 diabetes mellitus who have not previously achieved adequate glycemic control with lifestyle modification (diet/exercise) or metformin antidiabetic monotherapy. Study participation is anticipated to be up to 20 weeks.

Being tested
SYR-472, Placebo, Sitagliptin
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
Medical subject headings
Diabetes Mellitus, Glucose Metabolism Disorders, Diabetes Mellitus, Type 2, Diabetes Mellitus, Lipoatrophic, Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SYR-472Drug

    SYR-472 3.125 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.

  • SYR-472Drug

    SYR-472 12.5 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.

  • SYR-472Drug

    SYR-472 50 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.

  • SYR-472Drug

    SYR-472 100 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.

  • PlaceboDrug

    SYR-472 placebo-matching tablets, orally, once daily with lifestyle modification and/or metformin therapy for up to 12 weeks.

  • SitagliptinDrug

    Also called Januvia™

    Sitagliptin 100 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.

Study groups in NCT00760344
Study groupRoleWhat they receive
SYR-472 3.125 mg QDExperimental(with lifestyle modification and/or metformin stable dose therapy)
Receives: Drug: SYR-472
SYR-472 12.5 mg QDExperimental(with lifestyle modification and/or metformin stable dose therapy)
Receives: Drug: SYR-472
SYR-472 50 mg QDExperimental(with lifestyle modification and/or metformin stable dose therapy)
Receives: Drug: SYR-472
SYR-472 100 mg QDExperimental(with lifestyle modification and/or metformin stable dose therapy)
Receives: Drug: SYR-472
Placebo QDPlacebo comparator(with lifestyle modification and/or metformin stable dose therapy)
Receives: Drug: Placebo
Sitagliptin 100 mg QDActive comparator(with lifestyle modification and/or metformin stable dose therapy)
Receives: Drug: Sitagliptin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline in glycosylated hemoglobin

    Measured: Week 12 or Final Visit

Secondary outcomes (15)

  1. Change from baseline in glycosylated hemoglobin

    Measured: Weeks 4, 8 and 12 or Final Visit.

  2. Change from baseline in fasting plasma glucose

    Measured: Weeks 1, 2, 4, 8, and 12 or Final Visit

  3. Change from baseline in 1,5-Anhydroglucitol

    Measured: Weeks 2, 4, 8, and 12 or Final Visit.

  4. Change from baseline in Proinsulin

    Measured: Weeks 4, 8, and 12 or Final Visit.

  5. Change from baseline in Insulin

    Measured: Weeks 4, 8, and 12 or Final Visit.

  6. Change from baseline in Proinsulin/insulin ratio

    Measured: Weeks 4, 8, and 12 or Final Visit.

  7. Change from baseline in C-peptide

    Measured: Weeks 4, 8, and 12 or Final Visit.

  8. Change from baseline in Homeostasis model assessment of insulin resistance.

    Measured: Weeks: 4, 8, and 12 or Final Visit.

  9. Change from baseline in Homeostasis model assessment of beta-cell function.

    Measured: Weeks 4, 8, and 12 or Final Visit.

  10. Incidence of marked hyperglycemia (fasting plasma glucose greater than or equal to 200 mg/dL [11.10 mmol/L]).

    Measured: Weeks 4, 8 and 12 or Final Visit.

  11. Incidence of rescue.

    Measured: Weeks 1, 2, 4, 8, and 12 or Final Visit.

  12. Clinical response endpoint incidence of glycosylated hemoglobin less than or equal to 6.5%.

    Measured: Week 12 or Final Visit

  13. Clinical response endpoint incidence of glycosylated hemoglobin less than or equal to 7.0%.

    Measured: Week 12 or Final Visit

  14. Change from baseline in Fasting lipids (triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol).

    Measured: Weeks 4, 8, and 12 or Final Visit.

  15. Body weight.

    Measured: Weeks 4, 8, and 12 or Final Visit.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2008 (estimated)
  2. Study startMar 2007
  3. Primary completionMar 2008
  4. Study completionMar 2008

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
386 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00760344
Sponsor's protocol ID
01-06-TL-SYR-472-006
Other IDs
U1111-1129-7916
Status last verified
Jun 2016
First submitted
24 Sep 2008
Last updated
22 Jun 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SYR-472 and Sitagliptin in people with Diabetes Mellitus, run by Takeda at 112 sites in 2 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 18 inclusion and 16 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 22 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 112 sites in United States, Mexico. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 in glycosylated hemoglobin (time frame: Week 12 or Final Visit). 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 NCT00760344.

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 22 Jun 2016.

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