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

Study Overview
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Brief Summary
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This 4 arm study will assess the efficacy, safety and tolerability of taspoglutide compared to sitagliptin and placebo in patients with type 2 diabetes mellitus inadequately controlled with metformin. Patients will be randomized to receive taspoglutide (10mg once weekly or 10mg once weekly for 4 weeks followed by 20mg once weekly), sitagliptin 100mg once daily or placebo, in a ratio of 2:2:2:1, in addition to their continued prestudy metformin treatment. After 24 weeks of treatment, patients on active treatment will continue on the same treatment and 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 2+ years, and the target sample size is 500+ individuals.

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

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo (matching sitagliptin)
* Drug: Placebo (matching taspoglutide)
* Drug: Sitagliptin
* Drug: Taspoglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-75 years of age; type 2 diabetes receiving metformin (>=1500mg/day) for at least 12 weeks; HbA1c >=7.0% and <=10.0% at screening; BMI >=25 (>23 for Asians) and <=45kg/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>Once daily oral administration of placebo (matching sitagliptin). Once weekly sc injection of placebo (matching taspoglutide). Continued treatment with metformin at prescribed doses. | Drug: Metformin<br>* As prescribed<br>Drug: Placebo (matching sitagliptin)<br>* Once daily oral administration of placebo (matching sitagliptin).<br>Drug: Placebo (matching taspoglutide)<br>* Once weekly subcutaneous (sc) injection of placebo (matching taspoglutide).<br>|
| Active Comparator: Sitagliptin<br>Once daily oral administration of 100 mg of sitagliptin. Once weekly sc injection of placebo (matching taspoglutide). Continued treatment with metformin at prescribed doses. | Drug: Metformin<br>* As prescribed<br>Drug: Placebo (matching taspoglutide)<br>* Once weekly subcutaneous (sc) injection of placebo (matching taspoglutide).<br>Drug: Sitagliptin<br>* Once daily oral administration of 100 mg of sitagliptin.<br>|
| Experimental: Taspoglutide 10 mg<br>Once weekly subcutaneous (sc) injection of 10 mg of taspoglutide. Once daily oral administration of placebo (matching sitagliptin). Continued treatment with metformin at prescribed doses. | Drug: Metformin<br>* As prescribed<br>Drug: Placebo (matching sitagliptin)<br>* Once daily oral administration of placebo (matching sitagliptin).<br>Drug: Taspoglutide<br>* Once weekly subcutaneous (sc) injection of 10 mg or 20 mg of taspoglutide.<br>|
| Experimental: Taspoglutide up-titrated to 20 mg<br>Once weekly sc injection of 10 mg of taspoglutide for the first 4 weeks, then up-titrated to once weekly sc injection of 20 mg of taspoglutide from week 5 onwards. Once daily oral administration of placebo (matching sitagliptin). Continued treatment with metformin at prescribed doses. | Drug: Metformin<br>* As prescribed<br>Drug: Placebo (matching sitagliptin)<br>* Once daily oral administration of placebo (matching sitagliptin).<br>Drug: Taspoglutide<br>* Once weekly subcutaneous (sc) injection of 10 mg or 20 mg of taspoglutide.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean changes 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; change from baseline in lipid profile; beta cell function. |  | 24 weeks | 
| Safety: Adverse events, vital signs, physical examination, clinical laboratory tests, ECG and anti-taspoglutide antibodies. |  | Throughout study |