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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Obesity

Intervention / Treatment
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* Drug: BMS-646256
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |