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

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:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease

U.S. FDA Resources

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

More Information

No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2012 Feb 28.

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 May 21, 2013