Evaluate Safety and Effectiveness of MBX-102 in Type 2 Diabetes Patients With Poor Glycemic Control on Metformin

Study Overview
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Brief Summary
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To define the relative efficacy, safety and tolerability profiles of oral daily MBX-102 at daily doses of 400 and 600 mg vs. placebo and Actos® 30 mg (up-titrated to 45 mg after 8 weeks) when administered for up to 24 weeks in patients inadequately controlled with a stable dose of metformin (≥ 1500 mg/day).

Detailed Description
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Approximately 240 patients will be randomized in this study, 60 to each of two MBX-102 treatment groups (400 and 600 mg daily), 60 to placebo, and 60 to the Actos® group. Patients in the Actos® group will receive Actos® 30 mg/daily for the first eight weeks of the treatment phase and Actos® 45 mg/daily for the last 16 weeks of the treatment phase. Patients in the MBX-102 400 mg group and MBX-102 600 mg group will continue MBX-102 400 mg and 600 mg, respectively for the full 24 weeks. All study medication will be over-encapsulated; thus, each patient will take two blinded capsules each day containing either placebo, MBX-102 or Actos®. This sample size provides the minimum number expected to ensure a power of at least 90% in detecting a difference of 0.64% in HbA1c between the placebo and experimental treatment, using a two-tailed, two-sample t-test with type 1 error of 0.05, when the pooled standard deviation is ≤ 1.0%, and the discontinuation rate is ≤ 12.5%.

Official Title
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A Phase 2 Multicenter, Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Study to Evaluate the Safety and Efficacy of MBX-102/JNJ-39659100 in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: MBX-102
* Drug: Placebo
* Drug: Actos
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 2 diabetes who have been on metformin for the last 6 months and are taking a stable dose of metformin (≥ 1500 mg/d) as monotherapy for at least the last 3 months Male or female, 18-70 years of age All female patients must be surgically sterile or post-menopausal (at least 40 years of age with no history of menses for at least 2 years; or any age with no history of menses for at least 6 months and serum FSH ≥ 40 mIU/mL) or must agree to use two medically accepted methods of contraception including a barrier method. Depo contraceptives are excluded. Female patients must not be pregnant or lactating BMI ≥ 26 (patients of Asian Indian origin ≥ 22) kg/m2 HbA1c ≥ 7.5%, ≤ 10.5% FPG ≥ 120 mg/dL, ≤ 240 mg/dL Exclusion Criteria: History of diabetes secondary to pancreatitis or pancreatectomy Any history of ketoacidosis History of insulin use within last one year (insulin use while hospitalized is acceptable) Weight loss > 10 pounds in the three months prior to screening visit History of TZD use (Actos® or Avandia®) within 6 months of screening visit History of TZD discontinuation due to side effect or lack of efficacy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MBX-102 400<br> | Drug: MBX-102<br>* capsule<br>Drug: Metformin<br>* greater than or equal to 1500 mg/kg day<br>|
| Experimental: MBX-102 600<br> | Drug: MBX-102<br>* capsule<br>Drug: Metformin<br>* greater than or equal to 1500 mg/kg day<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* matching placebo<br>Drug: Metformin<br>* greater than or equal to 1500 mg/kg day<br>|
| Active Comparator: Actos<br>30-45 mg | Drug: Actos<br>* over-encapsulated to match MBX-102 and placebo<br>Drug: Metformin<br>* greater than or equal to 1500 mg/kg day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c from baseline and compared to placebo |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting plasma glucose (FPG) from baseline and vs. placebo |  | 24 weeks |