Safety Study to Evaluate BMS-767778 in Healthy Subjects and Subjects With Type 2 Diabetes Mellitus (T2DM)

Randomized, Double-Blind, Placebo-Controlled Ascending Single and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-767778 in Healthy Subjects and Subjects With Type 2 Diabetes Mellitus

To assess the safety and tolerability and the PK/PD relationship of BMS-767778 administered as single and multiple oral doses in healthy subjects, and in subjects with T2DM

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: BMS-767778 or Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1P 0A2
    • Local Institution

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

Parts A and Part B of the study (maximum age 45 years):

Inclusion Criteria:

• Healthy male and female subjects as determined by medical history, physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory evaluations will be eligible to participate in the study.
• Men and women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile)

Exclusion Criteria:

• Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations

Part C of the study (maximum age 65 years):

Inclusion criteria:

• Drug naive patients with T2DM or patients who are on metformin-monotherapy (at current dose for ≥ 8 weeks) with inadequately controlled blood glucose levels (HbA1c >7 %and <10 %) Men and women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile)

Exclusion criteria:

• Poorly controlled diabetes with either new onset or worsening of symptoms of polyuria and polydipsia, weight loss, fatigue, abdominal pain, or other significant signs and symptoms
• Any of the following medical conditions: uncontrolled hypertension, unstable angina pectora, Cushing's syndrome, Addison's disease, uncontrolled hyperthyroidism or hypothyroidism, significant liver disease or renal failure, malignant diseases, or immunodeficiency (e.g., HIV/AIDS or organ-transplant), or history of myocardial infarction, congestive heart failure defined as New York Heart Association (NYHA) stage II and above, significant valvular disease, cardiac arrhythmia, or transient ischemic attack or cerebrovascular accidents (occurred within 6 months prior to entry into the study), or family history of Long QT Syndrome

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; A: BMS-767778, Oral Solution, Oral, 1 mg, once daily, 1 day OR Placebo Comparator, Oral Solution, Oral, 0 mg, once daily, 1 day B: BMS-767778, Oral Solution, Oral, 3 mg, once daily, 1 day OR Placebo Comparator, Oral Solution, Oral, 0 mg, once daily, 1 day C: BMS-767778, Capsules, Oral, 10 mg, once daily, 1 day OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 1 day D: BMS-767778, Capsules, Oral, 30 mg, once daily, 1 day OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 1 day E: BMS-767778, Capsules, Oral, 100 mg, once daily, 1 day OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 1 day F: BMS-767778, Capsules, Oral, 300 mg, once daily, 2 days OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 2 days G: BMS-767778, Capsules, Oral, 600 mg, once daily, 1 day OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 1 day	Drug: BMS-767778 or Placebo
Experimental: Part B; A: BMS-767778, Capsules, Oral, 10 mg, once daily, 14 days OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 14 days B: BMS-767778, Capsules, Oral, 30 mg, once daily, 14 days OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 14 days C: BMS-767778, Capsules, Oral, 100 mg, once daily, 14 days OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 14 days D: BMS-767778, Capsules, Oral, 300 mg, once daily, 14 days OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 14 days E: BMS-767778, Capsules, Oral, 600 mg, once daily, 14 days OR Placebo Comparator, Capsules, Oral, 0 mg, once daily, 14 days	Drug: BMS-767778 or Placebo
Experimental: Part C; A: BMS-767778, Capsules, Oral, Adaptive design (between 10 to 600 mg), 14 days OR Placebo Comparator, Capsules, Oral, 0 mg, 14 days B: BMS-767778, Capsules, Oral, Adaptive design (between 10 to 600 mg), 14 days OR Placebo Comparator, Capsules, Oral, 0 mg, 14 days	Drug: BMS-767778 or Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AEs, vital signs, ECG and clinical laboratory test results	throughout the study

Secondary Outcome Measures

Outcome Measure	Time Frame
Single and multiple dose (14 days) PK	throughout the study
DPP-4 inhibition and incretin response	throughout the study

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: June 27, 2008
• First Submitted That Met QC Criteria: June 30, 2008
• First Posted (Estimate): July 1, 2008

Study Record Updates

• Last Update Posted (Estimate): February 10, 2009
• Last Update Submitted That Met QC Criteria: February 9, 2009
• Last Verified: February 1, 2009

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: MB116-001