Safety, Pharmacokinetics and Pharmacodynamics Study to Evaluate BMS-830216 in Obese Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, tolerability and effect on body weight and other obesity-related factors of different doses of BMS-830216, compared to placebo. The study will also determine the amount of BMS-830216 in the blood.

Official Title
-----------------
Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple-Dose and Parallel Arm Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-830216 (Prodrug of BMS-819881) in Obese Subjects

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Drug: BMS-830216
* Drug: BMS-830216
* Drug: BMS-830216
* Drug: BMS-830216
* Drug: BMS-830216
* Drug: BMS-830216
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obese subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations Body Mass Index (BMI) of 30 to 40 kg/m², inclusive Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) and men, ages 18 to 55, inclusive Exclusion Criteria: Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population Female of childbearing potential Sexually active fertile male not using effective birth control method (for example, condom) if your partners are females of childbearing potential Abnormal blood work results (for example, triglyceride ≥ 400 mg/dL, glucose ≥126 mg/dL and total cholesterol ≥ 300 mg/dL) High blood pressure (≥160/95 mm Hg) Major surgical procedure within 4 weeks prior to randomization Chronic infections (e.g., HIV [human immunodeficiency virus] or Hepatitis C) Clinically significant history or presence of any of the following conditions: heart, liver, or kidney disease, neurologic or psychiatric disease, or a previous surgery for weight loss History of gastrointestinal disease within the past 3 months History of Type I or Type II diabetes in the past 12 months A lifetime history of a suicide attempt or history of any suicidal behavior in the past month Any clinically significant medical condition that could potentially affect your participation in the study and/or personal well-being, as judged by the investigator Used grapefruit or grapefruit juice within 1 week prior to randomization Donated blood or blood products to a blood bank, blood transfusion or participated in a clinical study (except a screening visit) requiring withdrawal of blood within 4 weeks prior to randomization Unable to tolerate oral and/or intravenous (IV) medications Unable to tolerate the puncturing of veins for drawing of blood Prior exposure to BMS-830216 History of prior weight loss (for example, gastric bypass or gastric banding) or gastrointestinal surgery that could impact the absorption of study drug History of a Major Depressive Disorder within the past 2 years Known allergy or hypersensitivity to any component of the study medication History of any significant drug allergies (such as anaphylaxis or hepatotoxicity) Used any oral, injectable or implantable hormonal contraceptive agents (for example, birth control pills, Depo-Provera, or NuvaRing) within 3 months prior to randomization Used any prescription drugs or over the counter products to control acid (for example, Prevacid, Mylanta or Rolaids) within 4 weeks prior to randomization Used any prescription drugs, over the counter medications and herbal preparations within 1 week prior to randomization Taken St. John's Wort within 1 week prior to randomization Taken any investigational drug or placebo (inactive drug) within 4 weeks prior to randomization

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Panel A<br> | Drug: BMS-830216<br>* Capsules, Oral, 30 mg, once daily, 28 days<br>Drug: Placebo<br>* Capsules, Oral, 0 mg, once daily, 28 days<br>|
| Active Comparator: Panel B<br> | Drug: BMS-830216<br>* Capsules, Oral, 100 mg, once daily, 28 days<br>Drug: Placebo<br>* Capsules, Oral, 0 mg, once daily, 28 days<br>|
| Active Comparator: Panel C<br> | Drug: BMS-830216<br>* Capsules, oral, 300 mg, once daily, 28 days<br>Drug: Placebo<br>* Capsules, Oral, 0 mg, once daily, 28 days<br>|
| Active Comparator: Panel D<br> | Drug: BMS-830216<br>* Capsules, oral, 600 mg, once daily 28 days<br>Drug: Placebo<br>* Capsules, Oral, 0 mg, once daily, 28 days<br>|
| Active Comparator: Panel E<br> | Drug: BMS-830216<br>* Capsules, oral, 1200 mg, once daily, 28 days<br>Drug: Placebo<br>* Capsules, Oral, 0 mg, once daily, 28 days<br>|
| Active Comparator: Panel F<br>Low Dose | Drug: BMS-830216<br>* Capsules, Oral, to be determined, once daily, 28 days<br>|
| Active Comparator: Panel G<br>High Dose | Drug: BMS-830216<br>* Capsules, Oral, to be determined, once daily, 28 days<br>|
| Placebo Comparator: Panel H<br> | Drug: Placebo<br>* Capsules, Oral, 0 mg, once daily, 28 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: safety assessments will be based on adverse event reports and the results of vital sign measurements, electrocardiograms, physical examinations and clinical laboratory tests |  | Within 2 weeks after study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: to assess the multiple-dose PK of BMS-830216 |  | Within 2 weeks of study drug administration | 
| Pharmacodynamics: to assess the pharmacodynamic effect of BMS-830216 on body weight and BMI over 4 weeks of therapy |  | Within 2 weeks of study drug administration |