A Phase II, Multicenter, Double Blind, Placebo-Controlled Safety, Tolerability Study of BMS-708163 in Patients With Mild to Moderate Alzheimer's Disease - Full Text View

Purpose

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

Condition	Intervention	Phase
Alzheimer's Disease	Drug: BMS-708163 Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

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:

Adverse Events [ Time Frame: 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) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacodynamics effects of Cerebral Spinal Fluid [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: Yes ]
Pharmacodynamics effects of the Alzheimer's Disease Assessment Scale - Cognitive Subscale [ Time Frame: Baseline, Week 12, Week 24 and Week 36 ] [ Designated as safety issue: Yes ]
Pharmacodynamics effects of the Alzheimer's Disease Collaborative Study - Activities of Daily Living scale [ Time Frame: Baseline, Week 12, Week 24 and Week 36 ] [ Designated as safety issue: Yes ]
Pharmacodynamics effects of the Global clinical impression as assessed with the Clinical Dementia Rating-Sum of Boxes [ Time Frame: Baseline, Week 12, Week 24 and Week 36 ] [ Designated as safety issue: Yes ]
Characterize Pharmacodynamics/Pharmacokinetics effects of the plasma exposure of BMS-708163 and variability in a population with Alzheimer's disease [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: Yes ]
Characterize Pharmacodynamics/Pharmacokinetics effects in refining the Pharmacokinetics/Pharmacodynamics model with Phase 2 data [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: Yes ]
Characterize Pharmacodynamics/Pharmacokinetics effects by exploring correlations between exposure, biomarkers, and clinical effects [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: Yes ]
Characterize Pharmacodynamics/Pharmacokinetics effects by exploring Pharmacokinetics variability, including the correlation between polymorphisms of CYP enzymes [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: Yes ]

Enrollment:	209
Study Start Date:	February 2009
Study Completion Date:	June 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: A1	Drug: BMS-708163 Capsules, Oral, 25 mg, once daily, 24 weeks
Active Comparator: A2	Drug: BMS-708163 Capsules, Oral, 50 mg, once daily, 24 weeks
Active Comparator: A3	Drug: BMS-708163 Capsules, Oral, 100 mg, once daily, 24 weeks
Active Comparator: A4	Drug: BMS-708163 Capsules, Oral, 125 mg, once daily, 24 weeks
Placebo Comparator: A5	Drug: Placebo Capsules, Oral, 0 mg, once daily, 24 weeks

Eligibility

Ages Eligible for Study:	50 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00810147

Show 41 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

No publications provided by Bristol-Myers Squibb

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

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 γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol. 2012 Nov;69(11):1430-40.

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00810147 History of Changes
Other Study ID Numbers:	CN156-013, EUDRACT: 2008-005929-11
Study First Received:	December 16, 2008
Last Updated:	January 24, 2011
Health Authority:	United States: Food and Drug Administration Denmark: Danish Medicines Agency Sweden: Medical Products Agency Finland: Finnish Medicines Agency

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 June 17, 2013