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

Phase 2

Terminated

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: MBX-102; Drug: Actos; Drug: Metformin

• Registration Number: NCT00814372
• Lead Sponsor: CymaBay Therapeutics, Inc.

Brief Summary

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

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%.

Study Timeline

• Study Start: 2008-12
• Study First Submitted: 2008-12-22
• Study First Submitted QC: 2008-12-23
• Study First Posted: 2008-12-24
• Primary Completion: 2010-02
• Study Completion: 2010-02
• Disposition First Submitted: 2015-02-16
• Status Verified: 2015-03
• Disposition First Submitted QC: 2015-03-09
• Disposition First Posted: 2015-03-30
• Last Update Submitted: 2015-03-30
• Last Update Posted: 2015-04-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 242

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MBX-102 400	Metformin	-
Placebo	Placebo	-
Placebo	Metformin	-
Actos	Metformin	30-45 mg
MBX-102 600	MBX-102	-
Actos	Actos	30-45 mg
MBX-102 400	MBX-102	-
MBX-102 600	Metformin	-

Primary Outcome Measures

Name	Time	Method
Change in HbA1c from baseline and compared to placebo	24 weeks

Secondary Outcome Measures

Name	Time	Method
Change in fasting plasma glucose (FPG) from baseline and vs. placebo	24 weeks

Trial Locations

Locations (26)

Mediciti Hospital; 🇮🇳 Hyderabad, India

Diabetes Thyroid Hormone Research Institute Pvt. Ltd.; 🇮🇳 Indore, India

Fortis Hospital; 🇮🇳 Jaipur, India

Gandhi Endocrinology & Diabetes Centre; 🇮🇳 Nagpur, India

Amrita Institute of Medical Sciences; 🇮🇳 Kochi, India

Christian Medical College; 🇮🇳 Vellore, India

Deenanath Mangeshkar Hospital & Research Centre; 🇮🇳 Pune, India

Diabetes Care & Research Centre; 🇮🇳 Pune, India

All India Institute of Medical Sciences; 🇮🇳 New Delhi, India

PD Hindhuja National Hospital; 🇮🇳 Mumbai, India

Health & Research Centre; 🇮🇳 Trivendrum, India

Providence Clinical Research; 🇺🇸 Burbank, California, United States

Bharti Research Institute of Diabetes & Endocrinology; 🇮🇳 Karnal, India

Diabetes Action Centre; 🇮🇳 Mumbai, India

BYL Nair Hospital; 🇮🇳 Mumbai, India

Kamineni Hospitals Pvt, Ltd.; 🇮🇳 Hyderabad, Andhra Pradesh, India

Medwin Hospital; 🇮🇳 Hyderabad, India

M. S. Ramaiah Memorial Hospital; 🇮🇳 Bangalore, India

Piedmont Medical Research Associates; 🇺🇸 Winston-Salem, North Carolina, United States

Bangalore Diabetes Centre; 🇮🇳 Bangalore, India

Diacon Hospital Diabetes & Research Centre; 🇮🇳 Bangalore, India

St. John's Medical College & Hospital; 🇮🇳 Bangalore, India

Dr. V. Seshiah Diabetes Care & Research Institute; 🇮🇳 Chennai, India

Nevada Alliance Against Diabetes; 🇺🇸 Las Vegas, Nevada, United States

DGD Research, Inc.; 🇺🇸 San Antonio, Texas, United States

American Institute of Research; 🇺🇸 Los Angeles, California, United States