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

October 7, 2011
November 18, 2011
June 2007
March 2009   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01454115 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Study to Evaluate the Safety, Pharmacokinetics and Tolerability of BMS-708163
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

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Alzheimer's Disease
  • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    Oral Solution, Oral, 0.3 mg, Once daily, once
  • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    Oral Solution, Oral, 1.5 mg, Once daily, once
  • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    Oral Solution, Oral, 5.0 mg, Once daily, once
  • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    Oral Solution, Oral, 15.0 mg, Once daily, once
  • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    Oral Solution, Oral, 50 mg, Once daily, once
  • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    Oral Solution, Oral, 100 mg, Once daily, once
  • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    Oral Solution, Oral, 200 mg, Once daily, once
  • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    Oral Solution, Oral, 400 mg, Once daily, once
  • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    Capsule, Oral, 50 mg, Once daily, once
  • 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
  • Drug: Placebo matching BMS-708163
    Capsule, Oral, 0 mg, Once daily, once
  • Experimental: Panel 1: BMS-708163 or Placebo
    Healthy male subjects (age: 18 to 45 years)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 2: BMS-708163 or Placebo
    Healthy male subjects (age: 18 to 45 years)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 3: BMS-708163 or Placebo
    Healthy male subjects (age: 18 to 45 years)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 4: BMS-708163 or Placebo
    Healthy male subjects (age: 18 to 45 years)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • 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

    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 6: BMS-708163 or Placebo
    Healthy male subjects (age: 18 to 45 years)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 7: BMS-708163 or Placebo
    Healthy male subjects (age: 18 to 45 years)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 8: BMS-708163 or Placebo
    Healthy male subjects (age: 18 to 45 years)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 9: BMS-708163 or Placebo
    Healthy, elderly male subjects (age: 60 years and greater)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 10: BMS-708163 or Placebo
    Healthy, elderly female subjects (age: 60 years and greater)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 11: BMS-708163 or Placebo
    Healthy male subjects (age: between 46 to 59 years)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 12: BMS-708163 or Placebo
    Healthy male and/or female subjects or subjects with MCI (age: between 60-74 years)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 13: BMS-708163 or Placebo
    Healthy male and/or female subjects or with AD or MCI (age: 75 years or greater)
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
  • Experimental: Panel 15: BMS-708163 or Placebo
    Healthy young male subjects
    Interventions:
    • Drug: BMS-708163 (Gamma-Secretase Inhibitor)
    • Drug: Placebo matching BMS-708163
Tong G, Wang JS, Sverdlov O, Huang SP, Slemmon R, Croop R, Castaneda L, Gu H, Wong O, Li H, Berman RM, Smith C, Albright CF, Dockens RC. Multicenter, randomized, double-blind, placebo-controlled, single-ascending dose study of the oral γ-secretase inhibitor BMS-708163 (Avagacestat): tolerability profile, pharmacokinetic parameters, and pharmacodynamic markers. Clin Ther. 2012 Mar;34(3):654-67. doi: 10.1016/j.clinthera.2012.01.022. Epub 2012 Feb 28. PubMed PMID: 22381714.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
116
March 2009
March 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01454115
CN156-001
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP