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

Phase 3

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: exenatide, long acting release; Drug: exenatide

• Registration Number: NCT00308139
• Lead Sponsor: AstraZeneca

Brief Summary

A Randomized, Open-Label, Multicenter, Comparator-Controlled Study to Examine the Effects of Exenatide Long-Acting Release (LAR) on Glucose Control (HbA1c) and Safety in Subjects with Type 2 Diabetes Mellitus Managed with Diet Modification and Exercise and/or Oral Antidiabetic Medications.

Detailed Description

This trial is designed to examine the effect of exenatide once weekly compared to exenatide twice daily on glucose control and safety in subjects for at least 30 weeks. The study is also designed to examine glucose control during the transition from exenatide twice daily for 30 weeks to exenatide once weekly. Long-term safety and efficacy will be monitored during the open-ended assessment periods. This study will be conducted in approximately 300 subjects with type 2 diabetes treated with diet modification and exercise alone or in combination with a stable regimen of metformin, SU, thiazolidinedione (TZD), a combination of metformin and SU, a combination of metformin and TZD, or a combination of SU and TZD.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2006-03-27
• Study First Submitted QC: 2006-03-27
• Study First Posted: 2006-03-29
• Study Start: 2006-04
• Primary Completion: 2008-07
• Disposition First Submitted: 2011-06-17
• Disposition First Submitted QC: 2011-06-17
• Disposition First Posted: 2011-06-27
• Results First Submitted: 2012-02-14
• Results First Submitted QC: 2012-07-12
• Results First Posted: 2012-08-17
• Study Completion: 2014-08
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-29
• Last Update Posted: 2015-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 303

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exenatide Once Weekly	exenatide, long acting release	Subcutaneous injection (SC), once a week of long acting release (LAR) exenatide.
Exenatide Twice Daily	exenatide	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.

Primary Outcome Measures

Name	Time	Method
Change in HbA1c From Baseline to Week 30	Day -3, Week 30	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)	Week 22	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

Name	Time	Method
Change in HbA1c From Baseline to Week 364	Day -3, Week 364	Absolute change in HbA1c from Baseline (Day -3) to Week 364
Percentage of Subjects Achieving HbA1c Target of <7%	Week 364	Percentages of subjects achieving HbA1c target value of \<7% at Week 364
Percentage of Subjects Achieving HbA1c Target of <=6.5%	Week 364	Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 364
Percentage of Subjects Achieving HbA1c Target of <=6.0%	Week 30	Percentage of subjects achieving HbA1c target values of \<=6.0% at Week 30.
Exenatide LAR Steady State Concentration From Week 29 to Week 30	Week 29 to Week 30	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.
Change in 2 Hours (2h) Postprandial Glucose From Baseline to Week 14	Day -3, Week 14	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)	Week 22	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.
Change in Body Weight From Baseline to Week 30	Day -3, Week 30	Change in body weight from baseline (Day -3) to Week 30
Change in Fasting Plasma Glucose From Baseline to Week 30	Day -3, Week 30	Change in fasting plasma glucose from baseline (Day -3) to Week 30.
Change in Blood Pressure From Baseline to Week 30	Day -3, Week 30	Change in Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure from baseline to Week 30
Change in Body Weight From Baseline to Week 364	Day -3, Week 364	Change in body weight from baseline (Day -3) to Week 364
Change in Fasting Plasma Glucose From Baseline to Week 364	Day -3, Week 364	Change in fasting plasma glucose from baseline (Day -3) to Week 364.
Change in Total Cholesterol From Baseline to Week 364	Day -3, Week 364	Change in total cholesterol from baseline (Day -3) to Week 364.
Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 364	Day -3, Week 364	Change in high-density lipoprotein cholesterol (HDL-C) from baseline (Day -3) to Week 364.
Ratio of Triglycerides at Week 30 to Baseline	Day -3, Week 30	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.
Ratio of Triglycerides at Week 364 to Baseline	Day -3, Week 364	Ratio of triglycerides (measured in mg/dL) at Week 364 to baseline (Day -3). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.
Assessment on Event Rate of Treatment-emergent Hypoglycemic Events With SU Use at Screening	Day 1 to Week 364	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. 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.
Assessment on Event Rate of Treatment-emergent Hypoglycemic Events With Non-SU Use at Screening	Day 1 to Week 364	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. 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 Blood Pressure From Baseline to Week 364	Day -3, Week 364	Change in Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure from baseline to Week 364
Change in Total Cholesterol From Baseline to Week 30	Day -3, Week 30	Change in total cholesterol from baseline (Day -3) to Week 30.
Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 30	Day -3, Week 30	Change in high-density lipoprotein cholesterol (HDL-C) from baseline (Day -3) to Week 30.
Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 364	Day -3, Week 364	Change in low-density lipoprotein cholesterol (LDL-C) from baseline (Day -3) to Week 364.

Trial Locations

Locations (23)

Research Site; 🇨🇦 Toronto, Ontario, Canada

Research Site 023; 🇺🇸 Butte, Montana, United States

Research Site 518; 🇺🇸 San Diego, California, United States

Research Site 405; 🇺🇸 Cincinnati, Ohio, United States

Research Site 182; 🇺🇸 Encino, California, United States

Research Site 171; 🇺🇸 La Jolla, California, United States

Research Site 024; 🇺🇸 Walnut Creek, California, United States

Research Site 149; 🇺🇸 Indianapolis, Indiana, United States

Research Site 099; 🇺🇸 Lexington, Kentucky, United States

Research Site 312; 🇺🇸 St. Louis, Missouri, United States

Research Site 002; 🇺🇸 Durham, North Carolina, United States

Research Site 123; 🇺🇸 Winston-Salem, North Carolina, United States

Research Site 557; 🇺🇸 Marion, Ohio, United States

Research Site 053; 🇺🇸 Rochester, New York, United States

Research Site 152; 🇺🇸 Philadelphia, Pennsylvania, United States

Research Site 015; 🇺🇸 Dallas, Texas, United States

Research Site 009; 🇺🇸 San Antonio, Texas, United States

Research Site 108; 🇺🇸 Olympia, Washington, United States

Research Site 224; 🇺🇸 Minneapolis, Minnesota, United States

Research Site 231; 🇺🇸 Portland, Oregon, United States

Research Site 057; 🇺🇸 Miami, Florida, United States

Research Site 017; 🇺🇸 Detroit, Michigan, United States

Research Site 587; 🇺🇸 Greer, South Carolina, United States