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)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miramar, Florida, United States, 33025
      • Comprehensive Phase One
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

12

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: November 11, 2010
• First Submitted That Met QC Criteria: November 12, 2010
• First Posted (Estimate): November 15, 2010

Study Record Updates

• Last Update Posted (Estimate): March 15, 2012
• Last Update Submitted That Met QC Criteria: March 14, 2012
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: MB125-001