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

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

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).

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: MBX-102; Drug: Metformin; Drug: Actos

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 Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Bangalore, India
    • Bangalore Diabetes Centre
  • Bangalore, India
    • Diacon Hospital Diabetes & Research Centre
  • Bangalore, India
    • M. S. Ramaiah Memorial Hospital
  • Bangalore, India
    • St. John's Medical college & Hospital
  • Chennai, India
    • Dr. V. Seshiah Diabetes Care & Research Institute
  • Hyderabad, India
    • Mediciti Hospital
  • Hyderabad, India
    • Medwin Hospital
  • Indore, India
    • Diabetes Thyroid Hormone Research Institute Pvt. Ltd.
  • Jaipur, India
    • Fortis Hospital
  • Karnal, India
    • Bharti Research Institute of Diabetes & Endocrinology
  • Kochi, India
    • Amrita Institute of Medical Sciences
  • Mumbai, India, 400067
    • Diabetes Action Centre
  • Mumbai, India
    • BYL Nair Hospital
  • Mumbai, India
    • PD Hindhuja National Hospital
  • Nagpur, India
    • Gandhi Endocrinology & Diabetes Centre
  • New Delhi, India
    • All India Institute of Medical Sciences
  • Pune, India
    • Deenanath Mangeshkar Hospital & Research Centre
  • Pune, India
    • Diabetes Care & Research Centre
  • Trivendrum, India
    • Health & Research Centre
  • Vellore, India
    • Christian Medical College
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 50008
      • Kamineni Hospitals Pvt, Ltd.
• United States
  • California
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Los Angeles, California, United States, 90017
      • American Institute of Research
  • Nevada
    • Las Vegas, Nevada, United States, 89101
      • Nevada Alliance Against Diabetes
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research Associates
  • Texas
    • San Antonio, Texas, United States, 78229
      • Dgd Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: CymaBay Therapeutics, Inc.
• Investigators: Principal Investigator: Douglas Denham, M.D., Dgd Research, Inc.; Principal Investigator: Thomas W. Littlejohn, M.D., Piedmont Medical Research Associates; Principal Investigator: Michael Guice, M.D., American Institute of Research; Principal Investigator: K. M. Prasanna Kumar, MD, M. S. Ramaiah Memorial Hospital; Principal Investigator: Veerasamy Seshiah, MD, Dr. V. Seshiah Diabetes Care & Research Institute; Principal Investigator: Sanjay Kalra, MD, Bharti Research Institute of Diabetes & Endocrinology; Principal Investigator: Sailesh Lodha, MD, Fortis Hospital; Principal Investigator: Ariachery C Ammini, MD, All India Institute of Medical Sciences, New Delhi; Principal Investigator: Prema Varthakavi, MD, BYL Nair Hospital; Principal Investigator: Sanjiv Shah, MD, Diabetes Action Centre; Principal Investigator: Manoj Chadha, MD, PD Hindhuja National Hospital & Medical Research Centre; Principal Investigator: Mathew Thomas, MD, Health & Research Centre; Principal Investigator: Sanjay Reddy, MD, Bangalore Diabetes Centre; Principal Investigator: Ganapati Bantwal, MD, St Johns Medical College Hospital, Bangalore, India; Principal Investigator: Aravind S Sosale, MD, Diacon Hospital Diabetes & Research Centre; Principal Investigator: Vaishali Deshmukh, MD, Deenanath Mangeshkar Hospital & Research Centre; Principal Investigator: Abhay Mutha, MD, Diabetes Care & Research Centre; Principal Investigator: Nihal Thomas, MD, Christian Medical College, Vellore, India; Principal Investigator: Kirtikumar Modi, MD, Medwin Hospital; Principal Investigator: Sunil Jain, MD, Diabetes Thyroid Hormone Research Institute Pvt. Ltd.; Principal Investigator: Pramod Gandhi, MD, Gandhi Endocrinology & Diabetes Centre; Principal Investigator: Rakesh Kumar Sahay, MD, Mediciti Hospital; Principal Investigator: Harish Kumar, MD, Amrita Institute of Medical Sciences; Principal Investigator: Rubin Savedra, MD, Association of International Professionals, dba Nevada Alliance Against Diabetes; Principal Investigator: Teresa Sligh, MD, Translational Research Group, Inc. dba Providence Clinical Research; Principal Investigator: Prabha Adhikari, MD, Kasturba Medical College Hospital; Principal Investigator: Navneet Agrawal, MD, Diabetes, Obesity and Thyroid Center; Principal Investigator: Swamy Miryala, MD, Kamineni Hospitals Pvt, Ltd.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: December 22, 2008
• First Submitted That Met QC Criteria: December 23, 2008
• First Posted (Estimate): December 24, 2008

Study Record Updates

• Last Update Posted (Estimate): April 17, 2015
• Last Update Submitted That Met QC Criteria: March 30, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: M102-20814