A Multicenter, Double Blind, Placebo-Controlled, Safety and Tolerability Study of BMS-708163 in Patients With Prodromal 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 Prodromal Alzheimer's Disease

The purpose of this study is to determine the safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease over a treatment period of a minimum of 104-weeks. In addition patients will be seen for safety visits at 4 and 12 weeks post treatment.

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Avagacestat; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Local Institution
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • Local Institution
  • Ontario
    • London, Ontario, Canada, N6C 5J1
      • Local Institution
    • Toronto, Ontario, Canada, M5T 2S8
      • Local Institution
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Local Institution
• Denmark
  • Copenhagen, Denmark, 2100
    • Local Institution
• Finland
  • Turku, Finland, 20520
    • Local Institution
• France
  • Bordeaux Cedex, France, 33076
    • Local Institution
  • Dijon, France, 21033
    • Local Institution
  • Nantes, France, 44093
    • Local Institution
  • Rennes Cedex 9, France, 35033
    • Local Institution
  • Cedex 9
    • Toulouse, Cedex 9, France, 31059
      • Local Institution
• Sweden
  • 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
    • Peoria, Arizona, United States, 85381
      • Pivotal Research Centers
    • 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
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, Inc.
    • Los Angeles, California, United States, 90095
      • Mary S. Easton Center
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
    • San Diego, California, United States, 92103
      • Pacific Research Network
    • San Diego, California, United States, 92161
      • University of California, San Diego
    • San Diego, California, United States, 92108
      • Affiliated Research Institute
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc.
  • Colorado
    • Denver, Colorado, United States, 80239
      • Radiant Research, 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
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Inc
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • St Louis University
    • St. Louis, Missouri, United States, 63108
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center Of Amercia, Inc.
    • New Brunswick, New Jersey, United States, 08903
      • Robert Wood Johnson Medical School, Umdnj
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes, LLC
    • Toms River, New Jersey, United States, 08755
      • Memory Enhancement Center of NJ, Inc.
  • New York
    • Brooklyn, New York, United States, 11235
      • SPRI Clinical Trials, LLC
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates, PA
    • Raleigh, North Carolina, United States, 27609
      • Richard H. Weisler, Md, Pa & Assoc.
    • Winston Salem, North Carolina, United States, 27103
      • Clinical Trials of America, Inc.
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • 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
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
    • Portland, Oregon, United States, 97225
      • Providence Cognitive Assessment Clinic
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research (Sasr)
    • Dallas, Texas, United States, 75390
      • The University Of Texas
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Dean Foundation For Health Research & Education
    • Milwaukee, Wisconsin, United States, 53226
      • Mcw Clinics At Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient meets clinical criteria for prodromal Alzheimer's disease (MMSE 24-30)
• Memory complaint by subject or study partner
• CSF aβ42 levels < 200pg/mL or Total Tau/aβ42 ratio of ≥ 0.39
• Score of ≤4 on the Modified Hachinski Ischemia Scale
• CT results consistent with Alzheimer's disease
• Medically stable
• 6 years education
• Reliable study partner
• Must be able to swallow capsules

Exclusion Criteria:

• Premenopausal women
• DSM-IV diagnosis of Dementia 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
• 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Capsules, Oral, 0 mg, once daily, 104 - 220 Weeks
Experimental: Avagacestat (50 mg)	Drug: Avagacestat; Capsules, Oral, 50 mg, once daily, 104 - 220 Weeks; Other Names: BMS-708163

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease as measured by adverse events, vital signs, laboratory assessments, electrocardiograms (ECGs) and Safety Head Magnetic resonance imaging (MRI) findings	Every 12 weeks up to week 220
Safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease as measured by adverse events, vital signs, laboratory assessments, electrocardiograms (ECGs) and Safety Head Magnetic resonance imaging (MRI) findings	Avagacestat-treated patients will be seen for safety visits at 4 Post Treatment/Study Termination
Safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease as measured by adverse events, vital signs, laboratory assessments, electrocardiograms (ECGs) and Safety Head Magnetic resonance imaging (MRI) findings	Avagacestat-treated patients will be seen for safety visits at 12 Post Treatment/Study Termination
Safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease as measured by adverse events, vital signs, laboratory assessments, electrocardiograms (ECGs) and Safety Head Magnetic resonance imaging (MRI) findings	Avagacestat-treated patients will have a 24 week post treatment skin examination by a dermatologist

Secondary Outcome Measures

Outcome Measure	Time Frame
Predictive value of Cerebral Spinal Fluid (CSF) biomarkers (Aβ40, and Aβ42, total Tau, total Tau/Aβ42 ratio, phosphorylated Tau) on progression to dementia	Baseline (Week 0), Week 2 (optional), Week 24 and Week 104

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Coric V, Salloway S, van Dyck CH, Dubois B, Andreasen N, Brody M, Curtis C, Soininen H, Thein S, Shiovitz T, Pilcher G, Ferris S, Colby S, Kerselaers W, Dockens R, Soares H, Kaplita S, Luo F, Pachai C, Bracoud L, Mintun M, Grill JD, Marek K, Seibyl J, Cedarbaum JM, Albright C, Feldman HH, Berman RM. Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial. JAMA Neurol. 2015 Nov;72(11):1324-33. doi: 10.1001/jamaneurol.2015.0607.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: April 29, 2009
• First Submitted That Met QC Criteria: April 29, 2009
• First Posted (Estimate): April 30, 2009

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: CN156-018; 2009-010067-16 (EudraCT Number)