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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00308139
• Other study ID #: 2993LAR-105 (DURATION - 1)
• Secondary ID: MB001-010
• Status: Completed
• Phase: Phase 3
• First received: March 27, 2006
• Last updated: July 29, 2015
• Start date: April 2006
• Est. completion date: August 2014

Study information

• Verified date: July 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 303
• Est. completion date: August 2014
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• exenatide, long acting release

• exenatide

Locations

Country	Name	City	State
Canada	Research Site	Toronto	Ontario
United States	Research Site 023	Butte	Montana
United States	Research Site	Chicago	Illinois
United States	Research Site 405	Cincinnati	Ohio
United States	Research Site	Colorado Springs	Colorado
United States	Research Site 015	Dallas	Texas
United States	Research Site 017	Detroit	Michigan
United States	Research Site 002	Durham	North Carolina
United States	Research Site 182	Encino	California
United States	Research Site 587	Greer	South Carolina
United States	Research Site 149	Indianapolis	Indiana
United States	Research Site 171	La Jolla	California
United States	Research Site 099	Lexington	Kentucky
United States	Research Site 557	Marion	Ohio
United States	Research Site 057	Miami	Florida
United States	Research Site 224	Minneapolis	Minnesota
United States	Research Site 108	Olympia	Washington
United States	Research Site 152	Philadelphia	Pennsylvania
United States	Research Site 231	Portland	Oregon
United States	Research Site 053	Rochester	New York
United States	Research Site 009	San Antonio	Texas
United States	Research Site 518	San Diego	California
United States	Research Site 312	St. Louis	Missouri
United States	Research Site 024	Walnut Creek	California
United States	Research Site 123	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c From Baseline to Week 30	Absolute change in HbA1c from Baseline (Day -3) to Week 30 [Week 30 - Baseline]	Day -3, Week 30	No
Primary	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)	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	Week 22	No
Secondary	Change in HbA1c From Baseline to Week 364	Absolute change in HbA1c from Baseline (Day -3) to Week 364	Day -3, Week 364	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <7%	Percentage of subjects achieving HbA1c target value of <7% at Week 30.	Week 30	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <7%	Percentages of subjects achieving HbA1c target value of <7% at Week 364	Week 364	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <=6.5%	Percentages of subjects achieving HbA1c target values of <=6.5% at Week 30.	Week 30	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <=6.5%	Percentages of subjects achieving HbA1c target values of <=6.5% at Week 364	Week 364	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <=6.0%	Percentage of subjects achieving HbA1c target values of <=6.0% at Week 30.	Week 30	No
Secondary	Exenatide LAR Steady State Concentration From 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.	Week 29 to Week 30	No
Secondary	Change in 2 Hours (2h) Postprandial Glucose From Baseline to Week 14	Change in 2h Postprandial Glucose from baseline (Day -3) to Week 14	Day -3, Week 14	No
Secondary	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)	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.	Week 22	Yes
Secondary	Change in Body Weight From Baseline to Week 30	Change in body weight from baseline (Day -3) to Week 30	Day -3, Week 30	No
Secondary	Change in Body Weight From Baseline to Week 364	Change in body weight from baseline (Day -3) to Week 364	Day -3, Week 364	No
Secondary	Change in Fasting Plasma Glucose From Baseline to Week 30	Change in fasting plasma glucose from baseline (Day -3) to Week 30.	Day -3, Week 30	No
Secondary	Change in Fasting Plasma Glucose From Baseline to Week 364	Change in fasting plasma glucose from baseline (Day -3) to Week 364.	Day -3, Week 364	No
Secondary	Change in Blood Pressure From Baseline to Week 30	Change in Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure from baseline to Week 30	Day -3, Week 30	No
Secondary	Change in Blood Pressure From Baseline to Week 364	Change in Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure from baseline to Week 364	Day -3, Week 364	No
Secondary	Change in Total Cholesterol From Baseline to Week 30	Change in total cholesterol from baseline (Day -3) to Week 30.	Day -3, Week 30	No
Secondary	Change in Total Cholesterol From Baseline to Week 364	Change in total cholesterol from baseline (Day -3) to Week 364.	Day -3, Week 364	No
Secondary	Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 30	Change in high-density lipoprotein cholesterol (HDL-C) from baseline (Day -3) to Week 30.	Day -3, Week 30	No
Secondary	Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 364	Change in high-density lipoprotein cholesterol (HDL-C) from baseline (Day -3) to Week 364.	Day -3, Week 364	No
Secondary	Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 364	Change in low-density lipoprotein cholesterol (LDL-C) from baseline (Day -3) to Week 364.	Day -3, Week 364	No
Secondary	Ratio of Triglycerides at Week 30 to Baseline	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.	Day -3, Week 30	No
Secondary	Ratio of Triglycerides at Week 364 to Baseline	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.	Day -3, Week 364	No
Secondary	Assessment on Event Rate of Treatment-emergent Hypoglycemic Events With SU Use at Screening	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.	Day 1 to Week 364	Yes
Secondary	Assessment on Event Rate of Treatment-emergent Hypoglycemic Events With Non-SU Use at Screening	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.	Day 1 to Week 364	Yes