Study to Evaluate the Safety, Pharmacokinetics and Tolerability of BMS-708163

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01454115
First received: October 7, 2011
Last updated: November 18, 2011
Last verified: November 2011
  Purpose

The primary objective is to assess the safety and tolerability of a single oral dose of BMS-708163 in healthy young male subjects and in elderly male and female subjects.


Condition Intervention Phase
Alzheimer's Disease
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Drug: Placebo matching BMS-708163
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-708163 in Healthy Male Subjects and a Comparison to Elderly Male and Female Subjects

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety and tolerability of Single doses of BMS-708163 in the range of 0.3 to 800 mg in the healthy subjects [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: Yes ]
    Based on adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests


Secondary Outcome Measures:
  • Effects of BMS-708163 on cortisol and QT interval corrected for heart rate [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: Yes ]
  • Effect of BMS-708163 on thyroid stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and lymphocyte subsets [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: Yes ]
  • Bioavailability of BMS-708163 from a capsule formulation relative to a solution formulation [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: No ]
  • Effect of food on the PK of BMS-708163 administered as a capsule formulation [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) of BMS-708163 [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) of BMS-708163 [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-708163 [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-708163 [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: No ]
  • Plasma half-life (T-HALF) of BMS-708163 [ Time Frame: Within 28 days of dosing ] [ Designated as safety issue: No ]

Enrollment: 116
Study Start Date: June 2007
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panel 1: BMS-708163 or Placebo
Healthy male subjects (age: 18 to 45 years)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 0.3 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Experimental: Panel 2: BMS-708163 or Placebo
Healthy male subjects (age: 18 to 45 years)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 1.5 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Experimental: Panel 3: BMS-708163 or Placebo
Healthy male subjects (age: 18 to 45 years)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 5.0 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Experimental: Panel 4: BMS-708163 or Placebo
Healthy male subjects (age: 18 to 45 years)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 15.0 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Experimental: Panel 5: BMS-708163 or Placebo

Healthy male subjects (age: 18 to 45 years).

In Period 2: Subjects will receive BMS-708163 or placebo as a capsule formulation.

In Period 3: Subjects will receive BMS-708163 or placebo as a capsule formulation within 5 minutes of consuming a standard high-fat breakfast on Day 1

Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 50 mg, Once daily, once
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Capsule, Oral, 50 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Drug: Placebo matching BMS-708163
Capsule, Oral, 0 mg, Once daily, once
Experimental: Panel 6: BMS-708163 or Placebo
Healthy male subjects (age: 18 to 45 years)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 100 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Experimental: Panel 7: BMS-708163 or Placebo
Healthy male subjects (age: 18 to 45 years)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 200 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Experimental: Panel 8: BMS-708163 or Placebo
Healthy male subjects (age: 18 to 45 years)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 400 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Experimental: Panel 9: BMS-708163 or Placebo
Healthy, elderly male subjects (age: 60 years and greater)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 50 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Experimental: Panel 10: BMS-708163 or Placebo
Healthy, elderly female subjects (age: 60 years and greater)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 50 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once
Experimental: Panel 11: BMS-708163 or Placebo
Healthy male subjects (age: between 46 to 59 years)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Capsule, Oral, 50 mg, Once daily, once
Drug: Placebo matching BMS-708163
Capsule, Oral, 0 mg, Once daily, once
Experimental: Panel 12: BMS-708163 or Placebo
Healthy male and/or female subjects or subjects with MCI (age: between 60-74 years)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Capsule, Oral, 50 mg, Once daily, once
Drug: Placebo matching BMS-708163
Capsule, Oral, 0 mg, Once daily, once
Experimental: Panel 13: BMS-708163 or Placebo
Healthy male and/or female subjects or with AD or MCI (age: 75 years or greater)
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Capsule, Oral, 50 mg, Once daily, once
Drug: Placebo matching BMS-708163
Capsule, Oral, 0 mg, Once daily, once
Experimental: Panel 15: BMS-708163 or Placebo
Healthy young male subjects
Drug: BMS-708163 (Gamma-Secretase Inhibitor)
Oral Solution, Oral, 800 mg, Once daily, once
Drug: Placebo matching BMS-708163
Oral Solution, Oral, 0 mg, Once daily, once

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Panels 1- 8 and Panels 14-15: healthy male subjects between the ages of 18 to 45
  • Panels 9 and 10: healthy elderly males and females ages 60 and greater
  • Panel 11: healthy males between the ages of 46-59
  • Panel 12: males and/or females either healthy or with mild cognitive impairment (MCI) between the ages of 60 and 74
  • Panel 13: males and/or females, healthy or with Alzheimer's disease (AD) or MCI that were 75 years of age or greater
  • Acceptable medical history, physical examinations, vital signs, electrocardiograms, hemoccult stool tests, and clinical laboratory evaluations
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01454115

Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01454115     History of Changes
Other Study ID Numbers: CN156-001
Study First Received: October 7, 2011
Last Updated: November 18, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on April 16, 2014