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

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

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

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: BMS-708163; Drug: BMS-708163; Drug: BMS-708163; Drug: BMS-708163; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Local Institution
• Finland
  • Kuopio, Finland, 70210
    • Local Institution
  • Turku, Finland, 20520
    • Local Institution
• Sweden
  • Malmo, Sweden, 212 24
    • Local Institution
  • Molndal, Sweden, 431 41
    • Local Institution
  • Stockholm, Sweden, 141 86
    • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Phoenix, Arizona, United States, 85004
      • 21st Century Neurology
    • Sun City, Arizona, United States, 85351
      • Sun Health Research Institue
  • California
    • Fresno, California, United States, 93720
      • Margolin Brain Institute
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc.
    • Los Angeles, California, United States, 90024
      • Pacific Institute For Medical Research, Inc.
    • Los Angeles, California, United States, 90095
      • Mary S. Easton Center
    • San Diego, California, United States, 92103
      • Pacific Research Network, Inc
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc.
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School Of Medicine
    • Norwich, Connecticut, United States, 06360
      • Comprehensive Psychiatric Care
  • Florida
    • Brooksville, Florida, United States, 34601
      • Meridien Research
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • Tampa, Florida, United States, 33613
      • Usf Suncoast Alzheimer'S And Gerontology Center
    • Venice, Florida, United States, 34285
      • Center for Clinical Trials
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Inc
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center Of Amercia, Inc.
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes, LLC
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • Rochester, New York, United States, 14620
      • University of Rochester
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Richard H. Weisler, MD, PA & Associates
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Toledo, Ohio, United States, 43623
      • Neurology & Neuroscience Center Of Ohio
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Tulsa Clinical Research, LLC
  • Pennsylvania
    • Dunmore, Pennsylvania, United States, 18512
      • Professional Neurological Associates, Pc
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center LLC
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • R.I. Mood & Memory Research Institute
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • The University Of Texas
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Dean Foundation For Health Research & Education

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A1	Drug: BMS-708163; Capsules, Oral, 25 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 50 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 100 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 125 mg, once daily, 24 weeks
Active Comparator: A2	Drug: BMS-708163; Capsules, Oral, 25 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 50 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 100 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 125 mg, once daily, 24 weeks
Active Comparator: A3	Drug: BMS-708163; Capsules, Oral, 25 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 50 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 100 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 125 mg, once daily, 24 weeks
Placebo Comparator: A5	Drug: Placebo; Capsules, Oral, 0 mg, once daily, 24 weeks
Active Comparator: A4	Drug: BMS-708163; Capsules, Oral, 25 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 50 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 100 mg, once daily, 24 weeks; Drug: BMS-708163; Capsules, Oral, 125 mg, once daily, 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse Events	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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: December 16, 2008
• First Submitted That Met QC Criteria: December 16, 2008
• First Posted (Estimate): December 17, 2008

Study Record Updates

• Last Update Posted (Estimate): October 12, 2015
• Last Update Submitted That Met QC Criteria: September 23, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: CN156-013; EUDRACT: 2008-005929-11