Multiple-dose Study to Evaluate the Efficacy, Safety and Pharmacokinetics of BMS-646256 in Obese Subjects

A Randomized, Double-blind, Placebo-Controlled, Parallel Arm, Multiple-Dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BMS-646256 in Obese and High Risk Overweight Subjects

The purpose of this study is to learn if BMS-646256 can cause weight loss in men and women who are:

• overweight with high blood pressure or high cholesterol or
• obese

The safety of this treatment will also be studied

Study Overview

• Status: Terminated
• Conditions: Obesity
• Intervention / Treatment: Drug: BMS-646256; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 705
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Center for Human Nutrition
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Domenica M. Rubino, Md
  • Georgia
    • Augusta, Georgia, United States, 30909
      • CSRA Partners in Health, Inc
  • Illinois
    • Springfield, Illinois, United States, 62704
      • Springfield Diabetes and Endocrine Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • The Center For Nutrition & Preventive Medicine, Pllc
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Hampton Roads Center For Clinical Research Inc.
    • Richmond, Virginia, United States, 23294
      • National Clinical 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:

• Men and women, ages ≥18 to ≤70 years old with a Body Mass Index (BMI) ≥30 to ≤45 kg/m² OR BMI >27 to <30 kg/m² with hypertension and/or dyslipidemia defined as:
• Hypertension defined as treatment with an antihypertensive agent or mean systolic blood pressure ≥140 and ≤160 mmHg and/or diastolic blood pressure ≥ 90 and ≤ 105 mmHg
• Dyslipidemia defined as stable dose treatment with a statin, fibrate or ezetimibe for ≥ 6 weeks and/or triglycerides ≥ 150 and ≤ 600 mg/dL, LDL ≥ 130 and ≤ 300 mg/dL, or HDL < 40 mg/dL

Exclusion Criteria:

• Type 1 or 2 diabetes mellitus
• history of MI in the prior 6 months
• history of heart failure
• history of symptomatic arrhythmia
• active hepatic disease
• any documented muscle disease
• history of neurological symptoms or disease (including but not limited to tremor, ataxia, dizziness, neuropathy, or episodes of confusion, history of seizures, stroke or TIA)
• known history of major psychiatric conditions (e.g. schizophrenia anxiety disorder, dementia or bipolar disorder as defined by DSM IV criteria)
• history of depression or suicide attempt or ideation
• previous history of surgical procedures for weight loss (e.g., stomach stapling, bypass)
• uncontrolled blood pressure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T; 5 mg (ST) to 50 mg (LT)	Drug: BMS-646256; Tablet, Oral, Once Daily, 12 weeks treatment followed by 20 week washout (ST); up to 190 weeks treatment (LT)
Experimental: U; 10 mg (ST) to 50 mg (LT)	Drug: BMS-646256; Tablet, Oral, Once Daily, 12 weeks treatment followed by 20 week washout (ST); up to 190 weeks treatment (LT)
Experimental: V; 25 mg (ST) to 50 mg (LT)	Drug: BMS-646256; Tablet, Oral, Once Daily, 12 weeks treatment followed by 20 week washout (ST); up to 190 weeks treatment (LT)
Experimental: W; 50 mg (ST and LT)	Drug: BMS-646256; Tablet, Oral, Once Daily, 12 weeks treatment followed by 20 week washout (ST); up to 190 weeks treatment (LT)
Experimental: X; 25 mg/d (X1 wk), 5 mg/d (X11 wks) (ST) to 50 mg (LT)	Drug: BMS-646256; Tablet, Oral, Once Daily, 12 weeks treatment followed by 20 week washout (ST); up to 190 weeks treatment (LT)
Experimental: Z; Open label: 50 mg/d (X 4 wks) 100 mg/wk (X8 wks) (ST) to 50 mg (LT) Once daily (x 4 weeks), once daily (x 8 weeks)	Drug: BMS-646256; Tablet, Oral, Once Daily, 12 weeks treatment followed by 20 week washout (ST); up to 190 weeks treatment (LT)
Placebo Comparator: Y; 0 mg (ST and LT)	Drug: Placebo; Tablet, Oral, Once daily, 12 weeks treatment followed by 20 week washout (ST); up to 190 weeks treatment (LT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change in body weight from the start of the study	Average of Week 11 and 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in body weight	Average of Week 11 and 12
BMI	Change from baseline to Week 12, Week 32, and Week 44
waist circumference	Change from baseline to Week 12, Week 32, and Week 44
hormonal measures of insulin sensitivity and safety	Percent change from baseline to Week 12, Week 32, and Week 44
blood pressure	Change from baseline to Week 12, Week 32, and Week 44
blood lipids	Change from baseline to Week 12, Week 32, and Week 44
incidence of adverse events and lab abnormalities	throughout the study
Change and percent change in body weight	at Week 32 from baseline and Week 12
Time-matched change from baseline in QTc	at Week 12 and Week 32

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Solvay Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: October 5, 2006
• First Submitted That Met QC Criteria: October 16, 2006
• First Posted (Estimate): October 17, 2006

Study Record Updates

• Last Update Posted (Estimate): September 17, 2010
• Last Update Submitted That Met QC Criteria: September 15, 2010
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Other Study ID Numbers: MB109-007