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

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
BMS-708163 (Gamma-Secretase Inhibitor)
BMS-708163 (Gamma-Secretase Inhibitor)
BMS-708163 (Gamma-Secretase Inhibitor)
BMS-708163 (Gamma-Secretase Inhibitor)
BMS-708163 (Gamma-Secretase Inhibitor)
BMS-708163 (Gamma-Secretase Inhibitor)
BMS-708163 (Gamma-Secretase Inhibitor)
BMS-708163 (Gamma-Secretase Inhibitor)
BMS-708163 (Gamma-Secretase Inhibitor)
BMS-708163 (Gamma-Secretase Inhibitor)
Placebo matching BMS-708163
Placebo matching BMS-708163
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Alzheimer's Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm 9

    Arm 10

    Arm 11

    Arm 12

    Arm 13

    Arm 14

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Panel 1: BMS-708163 or Placebo

    Panel 2: BMS-708163 or Placebo

    Panel 3: BMS-708163 or Placebo

    Panel 4: BMS-708163 or Placebo

    Panel 5: BMS-708163 or Placebo

    Panel 6: BMS-708163 or Placebo

    Panel 7: BMS-708163 or Placebo

    Panel 8: BMS-708163 or Placebo

    Panel 9: BMS-708163 or Placebo

    Panel 10: BMS-708163 or Placebo

    Panel 11: BMS-708163 or Placebo

    Panel 12: BMS-708163 or Placebo

    Panel 13: BMS-708163 or Placebo

    Panel 15: BMS-708163 or Placebo

    Arm Description

    Healthy male subjects (age: 18 to 45 years)

    Healthy male subjects (age: 18 to 45 years)

    Healthy male subjects (age: 18 to 45 years)

    Healthy male subjects (age: 18 to 45 years)

    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

    Healthy male subjects (age: 18 to 45 years)

    Healthy male subjects (age: 18 to 45 years)

    Healthy male subjects (age: 18 to 45 years)

    Healthy, elderly male subjects (age: 60 years and greater)

    Healthy, elderly female subjects (age: 60 years and greater)

    Healthy male subjects (age: between 46 to 59 years)

    Healthy male and/or female subjects or subjects with MCI (age: between 60-74 years)

    Healthy male and/or female subjects or with AD or MCI (age: 75 years or greater)

    Healthy young male subjects

    Outcomes

    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
    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
    Effect of BMS-708163 on thyroid stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and lymphocyte subsets
    Bioavailability of BMS-708163 from a capsule formulation relative to a solution formulation
    Effect of food on the PK of BMS-708163 administered as a capsule formulation
    Maximum observed plasma concentration (Cmax) of BMS-708163
    Time of maximum observed plasma concentration (Tmax) of BMS-708163
    Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-708163
    Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-708163
    Plasma half-life (T-HALF) of BMS-708163

    Full Information

    First Posted
    October 7, 2011
    Last Updated
    November 18, 2011
    Sponsor
    Bristol-Myers Squibb
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01454115
    Brief Title
    Study to Evaluate the Safety, Pharmacokinetics and Tolerability of BMS-708163
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2011
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2007 (undefined)
    Primary Completion Date
    March 2009 (Actual)
    Study Completion Date
    March 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Bristol-Myers Squibb

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Alzheimer's Disease

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    116 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Panel 1: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male subjects (age: 18 to 45 years)
    Arm Title
    Panel 2: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male subjects (age: 18 to 45 years)
    Arm Title
    Panel 3: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male subjects (age: 18 to 45 years)
    Arm Title
    Panel 4: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male subjects (age: 18 to 45 years)
    Arm Title
    Panel 5: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    Panel 6: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male subjects (age: 18 to 45 years)
    Arm Title
    Panel 7: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male subjects (age: 18 to 45 years)
    Arm Title
    Panel 8: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male subjects (age: 18 to 45 years)
    Arm Title
    Panel 9: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy, elderly male subjects (age: 60 years and greater)
    Arm Title
    Panel 10: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy, elderly female subjects (age: 60 years and greater)
    Arm Title
    Panel 11: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male subjects (age: between 46 to 59 years)
    Arm Title
    Panel 12: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male and/or female subjects or subjects with MCI (age: between 60-74 years)
    Arm Title
    Panel 13: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy male and/or female subjects or with AD or MCI (age: 75 years or greater)
    Arm Title
    Panel 15: BMS-708163 or Placebo
    Arm Type
    Experimental
    Arm Description
    Healthy young male subjects
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Oral Solution, Oral, 0.3 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Oral Solution, Oral, 1.5 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Oral Solution, Oral, 5.0 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Oral Solution, Oral, 15.0 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Oral Solution, Oral, 50 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Oral Solution, Oral, 100 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Oral Solution, Oral, 200 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Oral Solution, Oral, 400 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Capsule, Oral, 50 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    BMS-708163 (Gamma-Secretase Inhibitor)
    Intervention Description
    Oral Solution, Oral, 800 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo matching BMS-708163
    Intervention Description
    Oral Solution, Oral, 0 mg, Once daily, once
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo matching BMS-708163
    Intervention Description
    Capsule, Oral, 0 mg, Once daily, once
    Primary Outcome Measure Information:
    Title
    Safety and tolerability of Single doses of BMS-708163 in the range of 0.3 to 800 mg in the healthy subjects
    Description
    Based on adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests
    Time Frame
    Within 28 days of dosing
    Secondary Outcome Measure Information:
    Title
    Effects of BMS-708163 on cortisol and QT interval corrected for heart rate
    Time Frame
    Within 28 days of dosing
    Title
    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
    Title
    Bioavailability of BMS-708163 from a capsule formulation relative to a solution formulation
    Time Frame
    Within 28 days of dosing
    Title
    Effect of food on the PK of BMS-708163 administered as a capsule formulation
    Time Frame
    Within 28 days of dosing
    Title
    Maximum observed plasma concentration (Cmax) of BMS-708163
    Time Frame
    Within 28 days of dosing
    Title
    Time of maximum observed plasma concentration (Tmax) of BMS-708163
    Time Frame
    Within 28 days of dosing
    Title
    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
    Title
    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
    Title
    Plasma half-life (T-HALF) of BMS-708163
    Time Frame
    Within 28 days of dosing

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Bristol-Myers Squibb
    Organizational Affiliation
    Bristol-Myers Squibb
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22381714
    Citation
    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 gamma-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.
    Results Reference
    derived

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

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