Effects of Exenatide Long-Acting Release on Glucose Control and Safety in Subjects With Type 2 Diabetes Mellitus(DURATION - 1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00308139
First received: March 27, 2006
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

This is a Pharmacokinetic (PK) sub-study to determine the relative bioavailability of exenatide when administered using the once weekly dual chambered pen and the once weekly single dose tray.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: exenatide, long acting release
Drug: exenatide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Multicenter, Comparator-Controlled Study to Examine the Effects of Exenatide Long-Acting Release on Glucose Control (HbA1c) and Safety in Subjects With Type 2 Diabetes Mellitus Managed With Diet Modification and Exercise and/or Oral Antidiabetic Medications

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Change in HbA1c From Baseline to Week 30 [ Time Frame: Day -3, Week 30 ] [ Designated as safety issue: No ]
    Absolute change in HbA1c from baseline (Day -3) to Week 30 [Week 30 - Baseline]

  • Sub-study Relative Bioavailability of Exenatide When Administered Using the Exenatide Once Weekly Dual Chambered Pen and the Exenatide Once Weekly Single Dose Tray (Single Dose Tray-11 Weekly Doses Switch to Dual Chamber Pen -11 Weekly Dose) [ Time Frame: Week 22 ] [ Designated as safety issue: No ]
    Measure by Geometric mean ratio (GMR) of plasma exenatide average steady state concentration Css,avg at Visit 11-14 to Visit 24-27 with 90% confidence interval


Secondary Outcome Measures:
  • Percentage of Subjects Achieving HbA1c Target of <7% [ Time Frame: Week 30 ] [ Designated as safety issue: No ]
    Percentages of subjects achieving HbA1c target value of <7% at Week 30.

  • Percentage of Subjects Achieving HbA1c Target of <=6.5% [ Time Frame: Week 30 ] [ Designated as safety issue: No ]
    Percentages of subjects achieving HbA1c target values of <=6.5% at Week 30.

  • Percentage of Subjects Achieving HbA1c Target of <=6.0% [ Time Frame: Week 30 ] [ Designated as safety issue: No ]
    Percentages of subjects achieving HbA1c target values of <=6.0% at Week 30.

  • Change in Body Weight From Baseline to Week 30 [ Time Frame: Day -3, Week 30 ] [ Designated as safety issue: No ]
    Change in body weight from baseline (Day -3) to Week 30

  • Change in Fasting Plasma Glucose From Baseline to Week 30 [ Time Frame: Day -3, Week 30 ] [ Designated as safety issue: No ]
    Change in fasting plasma glucose from baseline (Day -3) to Week 30.

  • Change in Blood Pressure From Baseline to Week 30 [ Time Frame: Day -3, Week 30 ] [ Designated as safety issue: No ]
    Change in Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure from baseline to Week 30

  • Change in Total Cholesterol From Baseline to Week 30 [ Time Frame: Day -3, Week 30 ] [ Designated as safety issue: No ]
    Change in total cholesterol from baseline (Day -3) to Week 30.

  • Change in High-density Lipoprotein (HDL) From Baseline to Week 30 [ Time Frame: Day -3, Week 30 ] [ Designated as safety issue: No ]
    Change in high-density lipoprotein (HDL) from baseline (Day -3) to Week 30.

  • Ratio of Triglycerides at Week 30 to Baseline [ Time Frame: Day -3, Week 30 ] [ Designated as safety issue: No ]
    Ratio of triglycerides (measured in mg/dL) at Week 30 to baseline (Day -3). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.

  • Exenatide LAR Steady State Concentration From Week 29 to Week 30 [ Time Frame: Week 29 to Week 30 ] [ Designated as safety issue: No ]
    Steady-state plasma exenatide concentration over the dosing interval of Week 29 to Week 30 (0-168 hours) was evaluated. Geometric mean for the average steady-state concentration and its 10th and 90th percentiles were reported.

  • Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events [ Time Frame: Day 1 to Week 30 ] [ Designated as safety issue: Yes ]
    The major hypoglycemia category included events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment, whether or not symptoms of hypoglycemia were perceived by the subject.

  • Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events [ Time Frame: Day 1 to Week 30 ] [ Designated as safety issue: Yes ]
    The minor hypoglycemia were accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment and not classified as major hypoglycemia.

  • Change in 2 Hours (2h) Postprandial Glucose From Baseline to Week 14 [ Time Frame: Day -3, Week 14 ] [ Designated as safety issue: No ]
    Change in 2h Postprandial Glucose from baseline (Day -3) to Week 14

  • Sub-study Safety and Tolerability of Exenatide When Administered Using the Once Weekly Single Dose Tray and the Once Weekly Dual (Single Dose Tray-11 Weekly Doses Switch to Dual Chamber Pen -11 Weekly Dose) [ Time Frame: Week 22 ] [ Designated as safety issue: Yes ]
    Measure by Geometric mean ratio of the maximum steady state plasma exenatide concentration Css, max at Visit 11-14 to Visit 24-27 with 90% confidence interval and Incidence of treatment-emergent injection site adverse events


Enrollment: 130
Study Start Date: April 2006
Estimated Study Completion Date: December 2014
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide Once Weekly
Subcutaneous injection (SC), once a week of long acting release (LAR) exenatide.
Drug: exenatide, long acting release
Other Name: BYDUREON
Active Comparator: Exenatide Twice Daily

subcutaneous injection (SC), twice a day for the first 30 weeks, followed by exenatide LAR SC injection weekly for the remainder of the study.

Sub-study: Exenatide 2 mg subcutaneous injection, Administered Using the Exenatide Once Weekly Single-Dose Tray , once a week for 11 visits, switch to Exenatide 2 mg subcutaneous injection, Administered Using the Dual chamber pen device. Exenatide 2mg SC injection administered using the Dual chamber pen device.

Drug: exenatide
Other Name: Byetta

Detailed Description:

Enrollment #: Original protocol Actual # of subjects: 303, Sub-study planned # of subjects: 130

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has type 2 diabetes mellitus treated with diet modification and exercise alone or in combination with a stable regimen of a combination of metformin, sulphonylureas, and thiazolidinediones for a minimum of 2 months at screening.
  • Hemoglobin A1c (HbA1c) of 7.1% to 11.0%, inclusive, at screening.
  • Body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening.
  • (For sub-study) Currently participating in open ended assessment period of main study 2993 LAR105

Exclusion Criteria:

  • Has been previously exposed to exenatide (Byetta®), exenatide LAR, or any glucagon-like peptide-1 (GLP-1) analog.
  • Received any investigational drug or has participated in any type of clinical trial within 30 days prior to screening.
  • Has been treated, is currently treated, or is expected to require or undergo treatment with any of the following excluded medications:

    • Alpha glucosidase inhibitor or meglitinide within 30 days of screening;
    • Insulin within 2 weeks prior to screening or insulin for longer than 1 week within 3 months of screening;
    • Regular use (> 14 days) of drugs that directly affect gastrointestinal motility;
    • Regular use (> 14 days) of systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary steroids known to have a high rate of systemic absorption;
    • Regular use (> 14 days) of medications with addictive potential such as opiates and opioids;
    • Prescription or over-the-counter weight loss medications within 6 months of screening.
  • (For sub-study) Subjects will be terminated from study who do not participate in the dual chamber pen substudy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00308139

  Show 25 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Lisa Porter, MD Amylin Pharmaceuticals, LLC.
  More Information

No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00308139     History of Changes
Other Study ID Numbers: 2993LAR-105 (DURATION - 1), MB001-010
Study First Received: March 27, 2006
Results First Received: February 14, 2012
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Bristol-Myers Squibb:
diabetes
exenatide
long acting release
LAR
Amylin
Lilly

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014