Clinical trial NCT00814372: Evaluate Safety and Effectiveness of MBX-102 in Type 2 Diabetes Patients With Poor Glycemic Control on Metformin
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2008-12-24
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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%.

Eligibility criteria: 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

Primary outcomes:
measure: Change in HbA1c from baseline and compared to placebo
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in fasting plasma glucose (FPG) from baseline and vs. placebo
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Burbank
country: United States
facility: Providence Clinical Research
state: California
city: Los Angeles
country: United States
facility: American Institute of Research
state: California
city: Las Vegas
country: United States
facility: Nevada Alliance Against Diabetes
state: Nevada
city: Winston-Salem
country: United States
facility: Piedmont Medical Research Associates
state: North Carolina
city: San Antonio
country: United States
facility: DGD Research, Inc.
state: Texas
city: Hyderabad
country: India
facility: Kamineni Hospitals Pvt, Ltd.
state: Andhra Pradesh
city: Bangalore
country: India
facility: Bangalore Diabetes Centre
city: Bangalore
country: India
facility: Diacon Hospital Diabetes & Research Centre
city: Bangalore
country: India
facility: M. S. Ramaiah Memorial Hospital
city: Bangalore
country: India
facility: St. John's Medical College & Hospital
city: Chennai
country: India
facility: Dr. V. Seshiah Diabetes Care & Research Institute
city: Hyderabad
country: India
facility: Mediciti Hospital
city: Hyderabad
country: India
facility: Medwin Hospital
city: Indore
country: India
facility: Diabetes Thyroid Hormone Research Institute Pvt. Ltd.
city: Jaipur
country: India
facility: Fortis Hospital
city: Karnal
country: India
facility: Bharti Research Institute of Diabetes & Endocrinology
city: Kochi
country: India
facility: Amrita Institute of Medical Sciences
city: Mumbai
country: India
facility: Diabetes Action Centre
city: Mumbai
country: India
facility: BYL Nair Hospital
city: Mumbai
country: India
facility: PD Hindhuja National Hospital
city: Nagpur
country: India
facility: Gandhi Endocrinology & Diabetes Centre
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
city: Pune
country: India
facility: Diabetes Care & Research Centre
city: Trivendrum
country: India
facility: Health & Research Centre
city: Vellore
country: India
facility: Christian Medical College
Study officials:
affiliation: dgd Research, Inc.
name: Douglas Denham, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Piedmont Medical Research Associates
name: Thomas W. Littlejohn, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: American Institute of Research
name: Michael Guice, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: M. S. Ramaiah Memorial Hospital
name: K. M. Prasanna Kumar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. V. Seshiah Diabetes Care & Research Institute
name: Veerasamy Seshiah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bharti Research Institute of Diabetes & Endocrinology
name: Sanjay Kalra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fortis Hospital
name: Sailesh Lodha, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: All India Institute of Medical Sciences
name: Ariachery C Ammini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: BYL Nair Hospital
name: Prema Varthakavi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diabetes Action Centre
name: Sanjiv Shah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: PD Hindhuja National Hospital & Medical Research Centre
name: Manoj Chadha, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Health & Research Centre
name: Mathew Thomas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bangalore Diabetes Centre
name: Sanjay Reddy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Johns Medical College Hospital, Bangalore, India
name: Ganapati Bantwal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diacon Hospital Diabetes & Research Centre
name: Aravind S Sosale, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Deenanath Mangeshkar Hospital & Research Centre
name: Vaishali Deshmukh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diabetes Care & Research Centre
name: Abhay Mutha, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Christian Medical College, Vellore, India
name: Nihal Thomas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medwin Hospital
name: Kirtikumar Modi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diabetes Thyroid Hormone Research Institute Pvt. Ltd.
name: Sunil Jain, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gandhi Endocrinology & Diabetes Centre
name: Pramod Gandhi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mediciti Hospital
name: Rakesh Kumar Sahay, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Amrita Institute of Medical Sciences
name: Harish Kumar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Association of International Professionals, dba Nevada Alliance Against Diabetes
name: Rubin Savedra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Translational Research Group, Inc. dba Providence Clinical Research
name: Teresa Sligh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kasturba Medical College Hospital
name: Prabha Adhikari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diabetes, Obesity and Thyroid Center
name: Navneet Agrawal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kamineni Hospitals Pvt, Ltd.
name: Swamy Miryala, MD
role: PRINCIPAL_INVESTIGATOR
References: