AzTrials
AzTrials

Type 2 DiabetesPhase 1NCT01664624

Roflumilast Plus Alogliptin Proof-of-Mechanism Study in Type2 Diabetes

A Phase 1 study testing Roflumilast, Alogliptin and Exenatide in people with Type 2 Diabetes, run by AstraZeneca at 2 sites in United States.

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 assess the effect of roflumilast plus alogliptin on glucagon-like peptide-1 (GLP-1) and glucose levels in patients with type 2 diabetes. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Type 2 Diabetes
What is being tested?
Roflumilast, Alogliptin and Exenatide
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
2 sitesUnited States
Study dates
Jul 2012to Nov 2012
Phase
Phase 1
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

  • Male or female, aged 18 to 80 years, inclusive, at the time of dosing on Day 1.
  • Has an historical diagnosis of type 2 diabetes mellitus (T2DM) disease.
  • Has a documented history of a diet and exercise plan and is receiving metformin as monotherapy at a stable dose for at least 8 weeks prior to Screening; has no chronic use (>7 days) of any other antidiabetic therapy within the 8 weeks prior to Screening.
  • Has inadequate glycemic control at Screening, as evidenced by HbA1c (glycosylated hemoglobin) level between 7.0% and 10.0%, inclusive.
  • Has a body mass index (BMI) of ≥23.0 kg/m^2 and ≤45.0 kg/m^2, at Screening.
  • A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose of study drug.
Show all 9Show fewer
  • A male who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose of study drug
  • In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
  • The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

Who cannot join

  • Has a history of type 1 diabetes.
  • Has a history of acute metabolic diabetic complications.
  • Has has abnormal Screening or Check-in (Day -2) laboratory values that suggest a clinically significant underlying disease (eg, active liver disease or jaundice) or participant with the following laboratory abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN).
  • Has a history of diabetic gastroparesis or history of gastric bypass surgery.
  • Has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.
  • Has New York Heart Association heart failure of Class (III-IV) regardless of therapy.
Show all 24Show fewer
  • Has a supine blood pressure >150 mm Hg for systolic or >90 mm Hg for diastolic, confirmed on repeat testing within a maximum of 5 minutes, at Screening and Check-in (Day -2).
  • Has presence or history of neuropsychiatric disorder (eg, psychosis, psychotic disorders, depression associated with suicidal thinking, suicidal ideation or behavior).
  • Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years or is unwilling to agree to abstain from alcohol and drugs throughout the study.
  • Has a hemoglobin ≤120 g/L for men and ≤100 g/L for women.
  • Has a history of clinically significant allergies or idiosyncrasies to roflumilast, alogliptin and exenatide or any inactive ingredient(s) of these products, eg, rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or phenylketonuria.
  • Has received alogliptin or roflumilast in a previous clinical study or as a therapeutic agent within 2 months prior to Screening, or is taking prescription roflumilast for chronic obstructive pulmonary disease (COPD), or has received any other investigational compound within 30 days prior to the first dose of study medication, or is participating or plans to participate in any other clinical trial during this study.
  • If female, is pregnant or lactating or intending to become pregnant before, during, or within 30 days after last dose; or intending to donate ova during such time period.
  • If male, intends to donate sperm during the course of the study or for 30 days after last dose of study medication.
  • Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
  • Has a history of cancer, except basal cell or squamous cell carcinoma which has been in remission for at least 5 years prior to Day 1.
  • Serum creatinine ≥1.5 mg/dL for males and ≥1.4 mg/dL for females or creatinine clearance <60 mL/minutes, based on calculation by central lab using the Cockcroft-Gault approximation at Screening Visit.
  • Has a history of any hemoglobinopathy that may affect determination of HbA1c.
  • Has positive test result for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV), any known history of infection with human immunodeficiency virus (HIV), any acute infection, or severe immunological diseases (eg, multiple sclerosis, systemic lupus erythematosus, and progressive multifocal leukoencephalopathy).
  • Has a risk of suicide according to the Investigator's clinical judgment per Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or has made a suicide attempt in the past 6 months.
  • Has any clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation (as assessed by the investigator).
  • Does not have an adequate standard of literacy to allow him or her to complete the study diary during non-clinic days.
  • Has poor peripheral venous access.
  • Has Screening or Check-in (Day -2) abnormal clinically significant electrocardiogram (ECG). Entry of any participant with abnormal not clinically significant ECG must be approved and documented by signature of Principal Investigator and Medical Monitor.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Study site

    Chula Vista, California

  • Study site

    Orlando, Florida

Other trials in United States

About this study

Official title: A Phase 1b, Randomized, Double-Blind, Active Comparator (Open-Label Exenatide) Controlled Study to Evaluate the Effect of Roflumilast Plus Alogliptin on Postprandial Active GLP-1 Level and 24-hour Glucose Level in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on a Stable Dose of Metformin

The purpose of this study is to assess the effect of roflumilast plus alogliptin on glucagon-like peptide-1 (GLP-1) and glucose levels in patients with type 2 diabetes.

Read the detailed description

This is a study to evaluate the antiglycemic efficacy and safety of roflumilast + alogliptin compared to alogliptin alone and roflumilast alone; it will also include an open-label exenatide treatment arm as a control. The antiglycemic efficacy of the combination will be evaluated through the measurement of postprandial active GLP-1 level, ß cell secretion activity (via the measurement of C-peptide and insulin levels), appetite sensations (as assessed by VAS) and glycemic control as assessed by a continuous glucose monitoring system (CGMS).

Conditions
Type 2 Diabetes
Being tested
Roflumilast, Alogliptin, Exenatide, Placebo to roflumilast, Placebo to alogliptin
Keywords
Drug Therapy
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

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

  • RoflumilastDrug

    Also called Daxas, Daliresp

    Roflumilast tablets

  • AlogliptinDrug

    Also called Nesina

    Alogliptin tablets

  • ExenatideDrug

    Also called Byetta, Bydureon

    Exenatide solution

  • Placebo to roflumilastDrug

    Placebo-matching roflumilast tablets

  • Placebo to alogliptinDrug

    Placebo-matching alogliptin tablets

Study groups in NCT01664624
Study groupRoleWhat they receive
Roflumilast + alogliptinExperimentalRoflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.
Receives: Drug: Roflumilast; Drug: Alogliptin
Alogliptin aloneExperimentalPlacebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.
Receives: Drug: Alogliptin; Drug: Placebo to roflumilast
Roflumilast aloneExperimentalRoflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.
Receives: Drug: Roflumilast; Drug: Placebo to alogliptin
ExenatideActive comparatorExenatide 5 μg subcutaneous injection twice a day for 11 days.
Receives: Drug: Exenatide

What is being measured

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

  1. Change From Baseline in Postprandial Area Under the Curve From Time 0 to 8 Hours (AUC[0-8]) for Active Glucagon-like Peptide-1

    The concentration of glucagon-like peptide-1 (GLP-1) in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an analysis of covariance (ANCOVA) model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of active GLP-1 as a continuous covariate.

    Measured: Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).

Secondary outcomes (5)

  1. Change From Baseline in AUC(0-8) of Postprandial Plasma Glucose

    The concentration of glucose in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and baseline postprandial AUC (0-8) of plasma glucose as a continuous covariate.

    Measured: Baseline and Day 11 at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).

  2. Change From Baseline in Postprandial AUC(0-8) of C-peptide

    The concentration of C-peptide in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of C-peptide as a continuous covariate.

    Measured: Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).

  3. Change From Baseline in Postprandial AUC(0-8) of Insulin

    The concentration of insulin in blood before and up to 8 hours after eating was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of insulin as a continuous covariate.

    Measured: Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).

  4. Change From Baseline to Day 11 in AUC(0-8) of Appetite Sensation

    Appetite sensations were measured using a visual analog scale (VAS) questionnaire. Participants were asked to indicate their level of fullness, hunger, satiety, and prospective consumption (how much do you think you can eat?) on a 100 mm line ranging from "Not at all" (0 mm) to "extremely" (100 mm). Appetite sensation scores before and up to 8 hours after eating were plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of appetite sensation VAS score as a continuous covariate.

    Measured: At Baseline and Day 11, every 30 minutes, starting 1 hour before eating until 8 hour after the meal.

  5. Change From Baseline to Day 11 in 24-hour Average Plasma Glucose

    Plasma glucose was measured by Continuous Glucose Monitoring System (CGMS). CGMS measures glucose every 5 minutes, starting in the fasting state 8 hour prior to the standardized breakfast (12 AM) until 16 hours after the breakfast. The average 24-hour plasma glucose concentration was calculated. Least squares means were obtained using an ANCOVA model with treatment as fixed effect, and Baseline 24-hour Glucose Measured by CGMS as a continuous covariate.

    Measured: Baseline (Day -1) and Day 11, from 12 AM through 24 hours.

Timeline

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

  1. First posted14 Aug 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionNov 2012
  4. Study completionNov 2012

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01664624
Sponsor's protocol ID
ROF-T2D_107
Other IDs
U1111-1128-6945
Status last verified
Sep 2016
First submitted
10 Aug 2012
Last updated
1 Feb 2017
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Roflumilast, Alogliptin and Exenatide in people with Type 2 Diabetes, run by AstraZeneca at 2 sites in United States.

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 9 inclusion and 24 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 1 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 20 Feb 2014). 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 in Postprandial Area Under the Curve From Time 0 to 8 Hours (AUC[0-8]) for Active Glucagon-like Peptide-1 (time frame: Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).). 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 NCT01664624.

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 1 Feb 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in