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

CymaBay Therapeutics

Status and phase: Terminated; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo; Drug: Metformin; Drug: MBX-102; Drug: Actos

Study type: Interventional

Funder types: Industry

Identifiers

NCT00814372

M102-20814

Details and patient eligibility

About

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).

Full description

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%.

Enrollment: 242 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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242 participants in 4 patient groups, including a placebo group

MBX-102 400

Experimental group

Treatment:

Drug: MBX-102

Drug: Metformin

MBX-102 600

Experimental group

Treatment:

Drug: MBX-102

Drug: Metformin

Placebo

Placebo Comparator group

Treatment:

Drug: Metformin

Drug: Placebo

Actos

Active Comparator group

Description:

30-45 mg

Treatment:

Drug: Metformin

Drug: Actos