Clinical trial NCT01454115: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-10-18
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Safety and tolerability of Single doses of BMS-708163 in the range of 0.3 to 800 mg in the healthy subjects
timeFrame: Within 28 days of dosing
Secondary outcomes:
measure: Effects of BMS-708163 on cortisol and QT interval corrected for heart rate
timeFrame: Within 28 days of dosing
measure: Effect of BMS-708163 on thyroid stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and lymphocyte subsets
timeFrame: Within 28 days of dosing
measure: Bioavailability of BMS-708163 from a capsule formulation relative to a solution formulation
timeFrame: Within 28 days of dosing
measure: Effect of food on the PK of BMS-708163 administered as a capsule formulation
timeFrame: Within 28 days of dosing
measure: Maximum observed plasma concentration (Cmax) of BMS-708163
timeFrame: Within 28 days of dosing
measure: Time of maximum observed plasma concentration (Tmax) of BMS-708163
timeFrame: Within 28 days of dosing
measure: Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-708163
timeFrame: Within 28 days of dosing
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-708163
timeFrame: Within 28 days of dosing
measure: Plasma half-life (T-HALF) of BMS-708163
timeFrame: Within 28 days of dosing
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
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.