Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using a Thiazolidinedione or a Thiazolidinedione and Metformin

Phase 3

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: placebo; Drug: exenatide

• Registration Number: NCT00603239
• Lead Sponsor: AstraZeneca

Brief Summary

This study will assess safety and efficacy of exenatide in combination with a thiazolidinedione (TZD) and a TZD plus metformin over 26 weeks in adult patients with type 2 diabetes who have not achieved adequate glycemic control.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-01
• Study First Submitted: 2008-01-17
• Study First Submitted QC: 2008-01-28
• Study First Posted: 2008-01-29
• Primary Completion: 2009-07
• Study Completion: 2009-07
• Results First Submitted: 2010-07-20
• Results First Submitted QC: 2010-08-12
• Results First Posted: 2010-09-02
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-19
• Last Update Posted: 2015-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 165

Inclusion Criteria

• Diagnosed with type 2 diabetes
• If treated with a thiazolidinedione (TZD) alone, the TZD dose must have been stable for at least 120 days
• The dose of TZD must be: Rosiglitazone (≥4 mg/day) or pioglitazone (≥30 mg/day)
• The metformin dose has been stable for at least 90 days
• Have suboptimal glycemic control as evidenced by an HbA1c between 7.1% and 10.0%, inclusive.
• Have a body mass index (BMI): 25 kg/m2 < BMI < 45 kg/m2.

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Exclusion Criteria

• Have participated in this study previously or any other study using exenatide (AC2993/LY2148568) or glucagon-like peptide-1 (GLP-1) analogs, or have been previously treated with exenatide or GLP-1 analogs

• Have participated in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days of screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.

• Have been treated with exogenous insulin for more than 1 week within the 2 months prior to screening

• Used drugs for weight loss (e.g., orlistat, rimonabant, sibutramine, or similar over-the-counter medications) within 3 months prior to screening.

• Are currently treated with any of the following excluded medications:

  • Sulfonylurea or meglitinide derivatives (e.g., repaglinide or nateglinide) within 3 months prior to screening
  • Alpha-glucosidase inhibitor (e.g., miglitol or acarbose) within 3 months of screening
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin or vildagliptin) within 3 months prior to screening
  • Pramlintide acetate injection within 3 months prior to screening
  • Drugs that directly affect gastrointestinal motility, including, but not limited to: Metoclopramide, cisapride, and chronic macrolide antibiotics
  • Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding study start

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	-
Exenatide twice daily (BID)	exenatide	-

Primary Outcome Measures

Name	Time	Method
Change in Glycosylated Hemoglobin (HbA1c)	baseline and 26 weeks	Change in HbA1c from baseline to endpoint after 26 weeks of treatment (i.e., HbA1c at endpoint minus HbA1c at baseline)

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients Achieving HbA1c <= 7%	26 weeks	Percentage of intent-to-treat (ITT) patients who had HbA1c \> 7% at baseline that decreased to \<= 7% at endpoint (Week 26 or early discontinuation)
Percentage of Patients Achieving HbA1c <= 6.5%	26 weeks	Percentage of ITT patients who had achieved HbA1c \<= 6.5% at endpoint (Week 26 or early discontinuation)
Change in Fasting Serum Glucose (FSG)	baseline and 26 weeks	Change in FSG from baseline to endpoint (26 weeks)
Change in Body Weight	baseline and 26 weeks	Change in body weight from baseline to endpoint (26 weeks)
Change in Beta-cell Function	baseline and 26 weeks	Change in homeostatic model assessment-beta cell (HOMA-B) from baseline to endpoint (Week 26) (outcome measure is presented as the ratio of endpoint HOMA-B divided by baseline HOMA-B). HOMA-B is a measure of pancreatic beta-cell function.
Change in Waist Circumference	baseline and 26 weeks	Change in waist circumference from baseline to endpoint (26 weeks)
Change in Insulin Sensitivity.	baseline and 26 weeks	Change in homeostatic model assessment-insulin sensitivity (HOMA-S) from baseline to endpoint (26 weeks) (outcome measure is presented as the ratio of endpoint HOMA-S divided by baseline HOMA-S).
Number of Subjects Who Experienced an Episode of Minor Hypoglycemia	26 weeks	Overall number of subjects who experienced an episode of minor hypoglycemia.
Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score	baseline and 26 weeks	IWQOL-Lite analysis of change from baseline to endpoint (26 weeks). IWQOL-Lite is a 31-item questionnaire, assessing the domains of physical function, self-esteem, sexual life, public distress, and work. Response categories for each item range from 1 = "never true" to 5 = "always true."
Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score	baseline and 26 weeks	EQ-5D Score - change from baseline to endpoint (26 weeks). EQ-5D is a 5-item questionnaire used to characterize current health states. The tool and accompanying visual analog scale (VAS) assess 5 domains of quality of life, including mobility, self-care, usual activity, pain, and anxiety/depression. Weights are used to score the responses to the 5 domains, with 3 options possible in each domain: extreme problems, some/moderate problems, or no problems. Scores range from 0 to 1, with a score of 1 representing a perfect health state.

Trial Locations

Locations (1)

Research Site; 🇿🇦 Pretoria, South Africa