Japanese Phase 1 Multiple Ascending Dose Study

A Randomized, Placebo-Controlled, Double-Blinded, Multiple Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-823778 in Healthy Subjects and Patients With Type 2 Diabetes Mellitus

The purpose of this clinical study is to assess the safety and tolerability of multiple oral doses of BMS-823778 in healthy Japanese subjects and Japanese patients with Type 2 Diabetes Mellitus.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: BMS-823778; Drug: BMS-823778; Drug: BMS-823778; Drug: BMS-823778; Drug: Placebo matching with BMS-823778

Detailed Description

MAD study - Multiple Ascending Dose study

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Hachioji-Shi, Tokyo, Japan, 1920071
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Japanese patients with Type 2 Diabetes Mellitus (T2DM) [Fasting glucose < 240 mg/dL, Hemoglobin A1c (HbA1c): 6.5% to 10.0% National Glycohemoglobin Standardization Program (NGSP)] who are treatment-naive and managed with diet and/or exercises only, ages: 20 to 65 years

Exclusion Criteria:

• Patient who is taking any medication for T2DM
• Symptoms of poorly controlled diabetes that would preclude participation in this placebo-controlled trial
• Insulin therapy within one year of screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel 1: BMS-823778 or Placebo matching BMS-823778; Healthy Subjects	Drug: BMS-823778; Capsules, Oral, 2 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 12 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 25 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 15 mg, Once daily, 14 days; Drug: Placebo matching with BMS-823778; Capsules, Oral, 0 mg, Once daily, 14 days
Experimental: Panel 2: BMS-823778 or Placebo matching BMS-823778; Healthy Subjects	Drug: BMS-823778; Capsules, Oral, 2 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 12 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 25 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 15 mg, Once daily, 14 days; Drug: Placebo matching with BMS-823778; Capsules, Oral, 0 mg, Once daily, 14 days
Experimental: Panel 3: BMS-823778 or Placebo matching BMS-823778; Healthy Subjects	Drug: BMS-823778; Capsules, Oral, 2 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 12 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 25 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 15 mg, Once daily, 14 days; Drug: Placebo matching with BMS-823778; Capsules, Oral, 0 mg, Once daily, 14 days
Experimental: Panel 4: BMS-823778 or Placebo matching BMS-823778; Subjects with T2DM	Drug: BMS-823778; Capsules, Oral, 2 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 12 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 25 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 15 mg, Once daily, 14 days; Drug: Placebo matching with BMS-823778; Capsules, Oral, 0 mg, Once daily, 14 days
Experimental: Panel 5: BMS-823778 or Placebo matching BMS-823778; Subjects with T2DM	Drug: BMS-823778; Capsules, Oral, 2 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 12 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 25 mg, Once daily, 14 days; Drug: BMS-823778; Capsules, Oral, 15 mg, Once daily, 14 days; Drug: Placebo matching with BMS-823778; Capsules, Oral, 0 mg, Once daily, 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability, as measured by the number, frequency and intensity of adverse events, vital sign measurements, ECGs, physical examinations, and clinical laboratory tests	Up to Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Trough observed plasma concentration (Cmin) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Time of maximum observed plasma concentration (Tmax) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Area under the plasma concentration-time curve in one dosing interval [AUC(TAU)] of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Accumulation Index following multiple dosing (AI) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Plasma half-life (T-HALF) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Percent urinary recovery (% UR) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Apparent total body clearance (CLT/F) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Renal clearance from plasma (CLR) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Peak to trough ratio (Cmax/Cmin) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Effective plasma half-life (T-HALFeff) of BMS-823778, as measured by plasma/urine concentration		Up to Day 21
Pharmacodynamics, as measured by Serum concentration of cortisol and cortisone after an oral dose of cortisone and biomarkers for HPA axis activity (urinary free cortisol and cortisone, salivary cortisol, ACTH, DHEA-S and 4-androstenedione)	HPA = Hypothalamic-pituitary-adrenal; DHEA-S = Dehydroepiandrosterone-sulphate; ACTH = adrenocorticotropic hormone	Up to Day 21

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: January 18, 2012
• First Submitted That Met QC Criteria: January 23, 2012
• First Posted (Estimate): January 24, 2012

Study Record Updates

• Last Update Posted (Estimate): December 5, 2012
• Last Update Submitted That Met QC Criteria: December 4, 2012
• Last Verified: December 1, 2012

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: MB121-009