Evaluation of the Effect on Glucose Control of AC2993 in Patients With Type 2 Diabetes Mellitus Treated With Metformin

Study Overview
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Brief Summary
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This is a multicenter, randomized, blinded, placebo-controlled study to assess the effects on glucose control of AC2993 as compared to placebo in patients with type 2 diabetes. Patients will be randomized into one of two AC2993 treatment arms or to placebo treatment and will continue with their required existing diabetes medication (metformin) throughout the study.

Official Title
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A Phase 3, Randomized, Triple-Blind, Parallel-Group, Long-Term, Placebo-Controlled, Multicenter Study to Examine the Effect on Glucose Control (HbA1c) of AC2993 Given Two Times a Day in Subjects With Type 2 Diabetes Mellitus Treated With Metformin Alone

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: AC2993
* Drug: AC2993
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with Type 2 diabetes mellitus Treated with metformin within a defined dose range for at least 3 months prior to screening BMI= 27-45 kg/m2 HbA1c value between 7.5% and 11% Exclusion Criteria: Treated with oral anti-diabetic medications other than metformin within 3 months of screening Patients treated previously with AC2993 Patients presently treated with insulin

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| Experimental: AC2993 5 mcg (0.02 mL)<br>Placebo, then AC2993 5 mcg, then AC2993 5 mcg | Drug: AC2993<br>* Placebo Lead In (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 26 weeks - All are subcutaneously injected twice daily<br>* Other names: synthetic exendin-4;|
| Experimental: AC2993 10mcg (0.04 mL)<br>Placebo, then AC2993 5 mcg, then AC2993 10 mcg | Drug: AC2993<br>* Placebo Lead In (0.02 mL) for 4 weeks / AC2993 5 mcg (0.02 mL) for 4 weeks / AC2993 10 mcg (0.04 mL) for 26 weeks - All are subcutaneously injected twice daily<br>* Other names: synthetic exendin-4;|
| Placebo Comparator: Placebo 0.02 mL<br>Placebo 0.02 mL, then Placebo 0.02 mL, then Placebo 0.02 mL | Drug: Placebo<br>* Placebo Lead In (0.02 mL) for 4 weeks / Placebo (0.02 mL) for 4 weeks / Placebo (0.02 mL) for 26 weeks - All are subcutaneously injected twice daily<br>|
| Placebo Comparator: Placebo 0.04 mL<br>Placebo 0.02 mL, then Placebo 0.02 mL, then Placebo 0.04 mL | Drug: Placebo<br>* Placebo Lead In (0.02 mL) for 4 weeks / Placebo mcg (0.02 mL) for 4 weeks / Placebo (0.04 mL) for 26 weeks - All are subcutaneously injected twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (glycosylated hemoglobin) from baseline to study termination (Week 30) | Change in HbA1c from from baseline, measured from Visit 3 (Day 1) to study termination (Week 30). | Baseline (Day 1), Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c from baseline (Day 1) to each of the intermediate visits | Change in HbA1c from baseline, measured from Visit 3 (Day 1) to each of the intermediate visits (Baseline (Day 1), Week 2, Week 4, Week, 6, Week 12, Week 18, and Week 24) | Baseline (Day 1), Week 2, Week 4, Week, 6, Week 12, Week 18, Week 24 | 
| The number of subjects achieving HbA1c target values of < 7% and < 8% by Week 30 | The number of subjects achieving HbA1c target values of < 7% and < 8% by study termination (Week 30) | Baseline (Day 1) and Week 30 | 
| The number of subjects achieving HbA1c reductions of > 0.5% and > 1.0% by Week 30 | The number of subjects achieving HbA1c reductions of > 0.5% and > 1.0% by study termination (Week 30) | Baseline (Day 1), and Week 30 | 
| The time to achieve specific HbA1c target values of < 7% and < 8% | The time it takes subjects to achieve HbA1c target values of < 7% and < 8% | Baseline (Day 1), Week 2, Week 4, Week, 6, Week 12, Week 18, Week 24, Week 30 | 
| The time to achieve HbA1c reductions of 0.5% or more and >1.0% or more | The time it takes subjects to achieve HbA1c reductions of 0.5% or more and >1.0% or more | Baseline (Day 1), Week 2, Week 4, Week, 6, Week 12, Week 18, Week 24, Week 30 | 
| Change in body weight from Baseline to each intermediate visit and Week 30 | Change in body weight (kg) from Baseline to each intermediate visit and Week 30 | Baseline (Day 1), Week 2, Week 4, Week, 6, Week 12, Week 18, Week 24, Week 30 |