A Study of Taspoglutide Versus Placebo for the Treatment of Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Plus Pioglitazone.

Study Overview
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Brief Summary
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This 3 arm study will assess the efficacy of taspoglutide on glycemic control (as assessed by HbA1c) in patients with type 2 diabetes mellitus inadequately controlled with metformin plus pioglitazone, compared to placebo after 24 weeks of treatment. Patients will be randomized to one of 3 treatment arms: taspoglutide 10mg once weekly, taspoglutide 20 mg once weekly (after 4 weeks of taspoglutide 10 mg once weekly) or placebo, in addition to their continued stable metformin plus pioglitazone treatment. After the first 24 weeks patients on placebo will be switched to taspoglutide 10mg once weekly or taspoglutide 20mg once weekly (after 4 weeks of taspoglutide 10mg once weekly. The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Effect of Taspoglutide on Glycemic Control Compared to Placebo in Patients With Type II Diabetes Mellitus Inadequately Controlled With Metformin Plus Pioglitazone

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: metformin
* Drug: pioglitazone
* Drug: placebo
* Drug: taspoglutide
* Drug: taspoglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-75 years age; type 2 diabetes receiving pioglitazone (>= 30 mg/day) and metformin (>= 1500 mg/day) for at least 12 weeks prior to screening; HbA1c >=7.0% and <=10.0% at screening; BMI >= 25 (>23 for Asians) and <=45 kg/m2 at screening; stable weight +/-5% for at least 12 weeks prior to screening. Exclusion Criteria: history of type 1 diabetes mellitus or acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma in the previous 6 months; evidence of clinically significant diabetic complications; clinically symptomatic gastrointestinal disease; myocardial infarction, coronary artery bypass surgery, post-transplantation cardiomyopathy or stroke within the previous 6 months; known hemoglobinopathy or chronic anemia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo in addition to continued stable metformin plus pioglitazone treatment. After the first 24 weeks patients on placebo will be switched to taspoglutide 10mg once weekly or taspoglutide 20mg once weekly (after 4 weeks of taspoglutide 10mg once weekly. | Drug: metformin<br>* >1500 mg/day or maximum tolerated dose (MTD)<br>Drug: pioglitazone<br>* >= 30 mg/day<br>Drug: placebo<br>* sc once weekly<br>Drug: taspoglutide<br>* 10 mg sc once weekly;<br>Drug: taspoglutide<br>* 20 mg sc once weekly (after 4 weeks of taspoglutide 10 mg sc once weekly)<br>|
| Experimental: Taspoglutide 10mg<br>Taspoglutide 10mg once weekly in addition to continued stable metformin plus pioglitazone treatment | Drug: metformin<br>* >1500 mg/day or maximum tolerated dose (MTD)<br>Drug: pioglitazone<br>* >= 30 mg/day<br>Drug: taspoglutide<br>* 10 mg sc once weekly;<br>|
| Experimental: Taspoglutide 10mg/20mg<br>Taspoglutide 20 mg once weekly (after 4 weeks of taspoglutide 10 mg once weekly) in addition to continued stable metformin plus pioglitazone treatment. | Drug: metformin<br>* >1500 mg/day or maximum tolerated dose (MTD)<br>Drug: pioglitazone<br>* >= 30 mg/day<br>Drug: taspoglutide<br>* 20 mg sc once weekly (after 4 weeks of taspoglutide 10 mg sc once weekly)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in HbA1c |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in fasting plasma glucose; change from baseline in body weight; responder rates for HbA1c (target <=7.0%, <=6.5%); responder rates for body weight; beta cell function. |  | 24 weeks | 
| Safety: adverse events, vital signs, physical examination, clinical laboratory tests, ECG and anti-taspoglutide antibodies. |  | Throughout the study |