Clinical trial NCT00810147: A Phase II, Multicenter, Double Blind, Placebo-Controlled Safety, Tolerability Study of BMS-708163 in Patients With Mild to Moderate Alzheimer's Disease
Official title: Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Effects of BMS-708163 in the Treatment of Patients With Mild to Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-12-17
Enrollment: 209
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and tolerability of BMS-708163 in patients with mild to moderate Alzheimer's disease over a treatment period of 12-weeks and the course of any potential effects during a 12-week wash-out period


Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of Mild to Moderate Alzheimer's disease (MMSE 16-26)
* 6 Month cognitive decline
* Stable marketed AD therapy x2 months or additional marketed AD therapy during study
* Score of \<=4 on the Modified Hachinski Ischemia Scale
* CT results consistent with Alzheimer's disease
* Medically stable
* 6 years education
* Reliable study partner (caregiver)
* Must be able to swallow capsules

Exclusion Criteria:

* Premenopausal women
* Dementia due to other causes than Alzheimer's disease
* History of stroke
* Immunocompromised
* Active peptic ulcer, GI bleed, chronic inflammatory bowel disease, chronic diarrhea or past GI surgery that would impact drug absorption
* Unstable Vitamin B-12 deficiency
* Hematologic or solid malignancy within 5 years
* Geriatric Depression Scale \>= 6
* Unstable medical condition
* Alcohol or drug abuse history with 12-months of study entry
* Significant drug allergy
* Alzheimer's disease modification experimental therapy with 12 months of study entry
* Prisoners, compulsory psychiatric patients, or residents of nursing home or skilled nursing facility at entry
* Any other experimental therapy with 30-days of study entry

Primary outcomes:
measure: Adverse Events
timeFrame: Weekly for the first 12-weeks of the 24-Week dosing period (Baseline-Week-12) and every 2 weeks during the second 12-weeks of the 24-Week dosing period (Weeks 14-24) and during the subsequent 12-week washout period (Weeks 28, 32, & 36)
Secondary outcomes:
measure: Pharmacodynamics effects of Cerebral Spinal Fluid
timeFrame: Baseline, Week 12 and Week 24
measure: Pharmacodynamics effects of the Alzheimer's Disease Assessment Scale - Cognitive Subscale
timeFrame: Baseline, Week 12, Week 24 and Week 36
measure: Pharmacodynamics effects of the Alzheimer's Disease Collaborative Study - Activities of Daily Living scale
timeFrame: Baseline, Week 12, Week 24 and Week 36
measure: Pharmacodynamics effects of the Global clinical impression as assessed with the Clinical Dementia Rating-Sum of Boxes
timeFrame: Baseline, Week 12, Week 24 and Week 36
measure: Characterize Pharmacodynamics/Pharmacokinetics effects of the plasma exposure of BMS-708163 and variability in a population with Alzheimer's disease
timeFrame: Baseline, Week 12 and Week 24
measure: Characterize Pharmacodynamics/Pharmacokinetics effects in refining the Pharmacokinetics/Pharmacodynamics model with Phase 2 data
timeFrame: Baseline, Week 12 and Week 24
measure: Characterize Pharmacodynamics/Pharmacokinetics effects by exploring correlations between exposure, biomarkers, and clinical effects
timeFrame: Baseline, Week 12 and Week 24
measure: Characterize Pharmacodynamics/Pharmacokinetics effects by exploring Pharmacokinetics variability, including the correlation between polymorphisms of CYP enzymes
timeFrame: Baseline, Week 12 and Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Phoenix
country: United States
facility: 21st Century Neurology
state: Arizona
city: Phoenix
country: United States
facility: Banner Alzheimer'S Institute
state: Arizona
city: Sun City
country: United States
facility: Sun Health Research Institue
state: Arizona
city: Fresno
country: United States
facility: Margolin Brain Institute
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, Inc.
state: California
city: Los Angeles
country: United States
facility: Pacific Institute For Medical Research, Inc.
state: California
city: Los Angeles
country: United States
facility: Mary S. Easton Center
state: California
city: San Diego
country: United States
facility: Pacific Research Network, Inc
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc.
state: California
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Norwich
country: United States
facility: Comprehensive Psychiatric Care
state: Connecticut
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Hallandale Beach
country: United States
facility: Md Clinical
state: Florida
city: Orlando
country: United States
facility: Compass Research, Llc
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Tampa
country: United States
facility: Usf Suncoast Alzheimer'S And Gerontology Center
state: Florida
city: Venice
country: United States
facility: Center For Clinical Trials
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Paducah
country: United States
facility: Four Rivers Clinical Research, Inc
state: Kentucky
city: Eatontown
country: United States
facility: Memory Enhancement Center Of Amercia, Inc.
state: New Jersey
city: Princeton
country: United States
facility: Global Medical Institutes, Llc
state: New Jersey
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University Of Rochester
state: New York
city: Raleigh
country: United States
facility: Richard H. Weisler, Md, Pa & Associates
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Toledo
country: United States
facility: Neurology & Neuroscience Center Of Ohio
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Clinical Research, Llc
state: Oklahoma
city: Dunmore
country: United States
facility: Professional Neurological Associates, Pc
state: Pennsylvania
city: Jenkintown
country: United States
facility: The Clinical Trial Center Llc
state: Pennsylvania
city: East Providence
country: United States
facility: R.I. Mood & Memory Research Institute
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Dallas
country: United States
facility: The University Of Texas
state: Texas
city: Middleton
country: United States
facility: Dean Foundation For Health Research & Education
state: Wisconsin
city: Odense
country: Denmark
facility: Local Institution
city: Kuopio
country: Finland
facility: Local Institution
city: Turku
country: Finland
facility: Local Institution
city: Malmo
country: Sweden
facility: Local Institution
city: Molndal
country: Sweden
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Coric V, van Dyck CH, Salloway S, Andreasen N, Brody M, Richter RW, Soininen H, Thein S, Shiovitz T, Pilcher G, Colby S, Rollin L, Dockens R, Pachai C, Portelius E, Andreasson U, Blennow K, Soares H, Albright C, Feldman HH, Berman RM. Safety and tolerability of the gamma-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol. 2012 Nov;69(11):1430-40. doi: 10.1001/archneurol.2012.2194.