Safety Study of BMS-903452 in Healthy Subjects (Panel 1-7) & Relative Bioavailability of the Crystalline and Amorphous Forms of BMS-903452 [Panels 4, 6, 11 & 12(Part A)], and Subjects With Type 2 Diabetes Mellitus (Part B)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability and effect on blood glucose control of BMS-903452 compared to placebo in healthy subjects & relative bioavailability of the crystalline and amorphous forms of BMS-903452 [Panels 4,6,11 & 12(Part A)] ; and subjects with type 2 Diabetes Mellitus (Part B). The study will also determine the amount of BMS-903452 in the blood.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-903452 in Healthy Subjects and Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes

Intervention / Treatment
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* Drug: BMS-903452
* Drug: BMS-903452
* Drug: BMS-903452
* Drug: BMS-903452
* Drug: BMS-903452
* Drug: BMS-903452
* Drug: BMS-903452
* Drug: Placebo
* Drug: Placebo
* Drug: BMS-903452
* Drug: BMS-903452
* Drug: Placebo
* Drug: BMS-903452
* Drug: BMS-903452
* Drug: BMS-903452


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically healthy or Clinical diagnosis of Type 2 diabetes on a stable dose of metformin monotherapy Exclusion Criteria: Type 1 Diabetes History of significant heart disease Prior bariatric surgery Women of childbearing potential

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: BMS-903452 (0.1 mg) or Placebo - A1<br>(Healthy Subjects) | Drug: BMS-903452<br>* Solution, Oral, 0.1 mg, once daily, 1 day<br>Drug: Placebo<br>* Solution, Oral, 0 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (0.6 mg) or Placebo - A2<br>(Healthy Subjects) | Drug: BMS-903452<br>* Solution, Oral, 0.6 mg, once daily, 1 day<br>Drug: Placebo<br>* Solution, Oral, 0 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (3.0 mg) or Placebo - A3<br>(Healthy Subjects) | Drug: BMS-903452<br>* Suspension, Oral, 3.0 mg, once daily, 1 day<br>Drug: Placebo<br>* Suspension, Oral, 0 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (10 mg) or Placebo - A4<br>(Healthy Subjects) | Drug: BMS-903452<br>* Suspension, Oral, 10 mg, once daily, 1 day<br>Drug: Placebo<br>* Suspension, Oral, 0 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (30 mg) or Placebo - A5<br>(Healthy Subjects) | Drug: BMS-903452<br>* Suspension, Oral, 30 mg, once daily, 1 day<br>Drug: Placebo<br>* Suspension, Oral, 0 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (60 mg) or Placebo - A6<br>(Healthy Subjects) | Drug: BMS-903452<br>* Suspension, Oral, 60 mg, once daily, 1 day<br>Drug: Placebo<br>* Suspension, Oral, 0 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (120 mg) or Placebo - A7<br>(Healthy Subjects) | Drug: BMS-903452<br>* Suspension, Oral, 120 mg, once daily, 1 day<br>Drug: Placebo<br>* Suspension, Oral, 0 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (0.6 mg) or Placebo - B1<br>(Subjects with type 2 Diabetes Mellitus) | Drug: Placebo<br>* Solution, Oral, 0 mg, once daily, 1 day<br>Drug: BMS-903452<br>* Solution, Oral, 0.6 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (10 mg) or Placebo - B2<br>(Subjects with type 2 Diabetes Mellitus) | Drug: Placebo<br>* Suspension, Oral, 0 mg, once daily, 1 day<br>Drug: BMS-903452<br>* Suspension, Oral, 10 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (120 mg) or Placebo - B3<br>(Subjects with type 2 Diabetes Mellitus) | Drug: Placebo<br>* Suspension, Oral, 0 mg, once daily, 1 day<br>Drug: BMS-903452<br>* Suspension, Oral, 120 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (10 mg) or Placebo - A11<br>(Healthy Subjects) | Drug: BMS-903452<br>* Suspension using crystalline form, Oral, 10 mg, once daily, 1 day<br>Drug: Placebo<br>* Suspension using crystalline form, Oral, 0 mg, once daily, 1 day<br>|
| Experimental: BMS-903452 (60 mg) or Placebo - A12<br>(Healthy Subjects) | Drug: BMS-903452<br>* Suspension using crystalline form, Oral, 60 mg, once daily, 1 day<br>Drug: Placebo<br>* Suspension using crystalline form, Oral, 0 mg, once daily, 1 day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of the investigational drug, as assessed by adverse event monitoring, physical examinations, clinical laboratory determinations, electrocardiograms (ECG), and vital sign assessments |  | Within 10 days of study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic activity of the investigational drug on glucose and hormones regulating glucose metabolism |  | Within 2 days of study drug administration | 
| Effect on electrocardiographic (ECG) parameters |  | Within 10 days of study drug administration | 
| Percent urinary recovery (% UR) | derived by non-compartmental methods by a validated pharmacokinetic program. Actual times will be used for the analyses | Within 10 days of study drug administration | 
| Renal clearance (CLR) from plasma | derived by non-compartmental methods by a validated pharmacokinetic program. Actual times will be used for the analyses | Within 10 days of study drug administration | 
| The single-dose pharmacokinetics parameter maximum observed concentration in plasma (Cmax) of BMS-903452 will be derived from the plasma concentration versus time data |  | Within 10 days after study drug administration | 
| The single-dose pharmacokinetics parameter time to reach maximum observed concentration in plasma (Tmax) of BMS-903452 will be derived from the plasma concentration versus time data |  | Within 10 days after study drug administration | 
| The single-dose pharmacokinetics parameter time Area under the plasma concentration-time curve from time zero extrapolated to infinity AUC(INF) of BMS-903452 will be derived from the plasma concentration versus time data |  | Within 10 days after study drug administration | 
| The single-dose pharmacokinetics parameter Area under the plasma concentration-time curve from time zero to last measurable sampling time AUC (0-T) of BMS-903452 will be derived from the plasma concentration versus time data |  | Within 10 days after study drug administration | 
| The single-dose pharmacokinetics parameter Terminal-phase elimination half-life in plasma (T-Half) of BMS-903452 will be derived from the plasma concentration versus time data |  | Within 10 days after study drug administration | 
| The single-dose pharmacokinetics parameter apparent clearance from plasma after extra-vascular administration (CLT/F) of BMS-903452 will be derived from the plasma concentration versus time data |  | Within 10 days after study drug administration |