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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00603239
• Other study ID #: H8O-MC-GWCG
• Status: Completed
• Phase: Phase 3
• First received: January 17, 2008
• Last updated: March 19, 2015
• Start date: January 2008
• Est. completion date: July 2009

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationMexico: Ministry of HealthSouth Africa: Medicines Control CouncilCanada: Health CanadaRomania: National Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• exenatide
subcutaneous injection, 5 mcg or 10 mcg, twice a day (BID)
• placebo
subcutaneous injection, volume equivalent to 5 mcg or 10 mcg of active drug, twice a day

Locations

Country	Name	City	State
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Cambridge	Ontario
Canada	Research Site	New Westminster	British Columbia
Canada	Research Site	Windsor	Ontario
Canada	Research Site	Winnipeg	Manitoba
Mexico	Research Site	Celaya	Guanajuato
Mexico	Research Site	Chihuahua
Mexico	Research Site	Mexico City
Mexico	Research Site	Mexico City	Distrito Federal
Mexico	Research Site	Monterrey	Nuevo Leon
Romania	Research Site	Baia Mare
Romania	Research Site	Brasov
Romania	Research Site	Bucuresti
Romania	Research Site	Dolj
Romania	Research Site	Iasi
Romania	Research Site	Suceava
South Africa	Research Site	Johannesburg
South Africa	Research Site	Pretoria
United States	Research Site	Birmingham	Alabama
United States	Research Site	Concord	California
United States	Research Site	Corvallis	Oregon
United States	Research Site	Denver	Colorado
United States	Research Site	Fresno	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Mogadore	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada,  Mexico,  Romania,  South Africa, 

References & Publications (1)

Liutkus J, Rosas Guzman J, Norwood P, Pop L, Northrup J, Cao D, Trautmann M. A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin. Diabetes Obes Metab. 2010 Dec;12(12):1058-65. doi: 10.1111 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated Hemoglobin (HbA1c)	Change in HbA1c from baseline to endpoint after 26 weeks of treatment (i.e., HbA1c at endpoint minus HbA1c at baseline)	baseline and 26 weeks	No
Secondary	Percentage of Patients Achieving HbA1c <= 7%	Percentage of intent-to-treat (ITT) patients who had HbA1c > 7% at baseline that decreased to <= 7% at endpoint (Week 26 or early discontinuation)	26 weeks	No
Secondary	Percentage of Patients Achieving HbA1c <= 6.5%	Percentage of ITT patients who had achieved HbA1c <= 6.5% at endpoint (Week 26 or early discontinuation)	26 weeks	No
Secondary	Change in Fasting Serum Glucose (FSG)	Change in FSG from baseline to endpoint (26 weeks)	baseline and 26 weeks	No
Secondary	Change in Body Weight	Change in body weight from baseline to endpoint (26 weeks)	baseline and 26 weeks	No
Secondary	Change in Waist Circumference	Change in waist circumference from baseline to endpoint (26 weeks)	baseline and 26 weeks	No
Secondary	Change in Beta-cell Function	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.	baseline and 26 weeks	No
Secondary	Change in Insulin Sensitivity.	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).	baseline and 26 weeks	No
Secondary	Number of Subjects Who Experienced an Episode of Minor Hypoglycemia	Overall number of subjects who experienced an episode of minor hypoglycemia.	26 weeks	No
Secondary	Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score	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."	baseline and 26 weeks	No
Secondary	Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score	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.	baseline and 26 weeks	No