Clinical trial NCT00890890: A Multicenter, Double Blind, Placebo-Controlled, Safety and Tolerability Study of BMS-708163 in Patients With Prodromal 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 Prodromal Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2009-04-30
Enrollment: 263
Sex: ALL
Minimum age (years): 45
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Every 12 weeks up to week 220
measure: 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
timeFrame: Avagacestat-treated patients will be seen for safety visits at 4 Post Treatment/Study Termination
measure: 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
timeFrame: Avagacestat-treated patients will be seen for safety visits at 12 Post Treatment/Study Termination
measure: 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
timeFrame: Avagacestat-treated patients will have a 24 week post treatment skin examination by a dermatologist
Secondary outcomes:
measure: Predictive value of Cerebral Spinal Fluid (CSF) biomarkers (Aβ40, and Aβ42, total Tau, total Tau/Aβ42 ratio, phosphorylated Tau) on progression to dementia
timeFrame: Baseline (Week 0), Week 2 (optional), Week 24 and Week 104
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Peoria
country: United States
facility: Pivotal Research Centers
state: Arizona
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: Long Beach
country: United States
facility: Collaborative Neuroscience Network, Inc.
state: California
city: Los Angeles
country: United States
facility: Mary S. Easton Center
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Institute
state: California
city: Orange
country: United States
facility: Uc Irvine Medical Center
state: California
city: San Diego
country: United States
facility: Pacific Research Network
state: California
city: San Diego
country: United States
facility: Affiliated Research Institute
state: California
city: San Diego
country: United States
facility: University Of California, San Diego
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc.
state: California
city: Denver
country: United States
facility: Radiant Research, Inc.
state: Colorado
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: 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: Boston
country: United States
facility: Brigham & Women'S Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: St Louis University
state: Missouri
city: St. Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center For Brain Health
state: Nevada
city: Eatontown
country: United States
facility: Memory Enhancement Center Of Amercia, Inc.
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School, Umdnj
state: New Jersey
city: Princeton
country: United States
facility: Global Medical Institutes, Llc
state: New Jersey
city: Toms River
country: United States
facility: Memory Enhancement Center Of Nj, Inc.
state: New Jersey
city: Brooklyn
country: United States
facility: Spri Clinical Trials, Llc
state: New York
city: New York
country: United States
facility: Nyu Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University Of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates, Pa
state: North Carolina
city: Raleigh
country: United States
facility: Richard H. Weisler, Md, Pa & Assoc.
state: North Carolina
city: Winston Salem
country: United States
facility: Clinical Trials Of America, Inc.
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School Of Medicine
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: Portland
country: United States
facility: Providence Cognitive Assessment Clinic
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Austin
country: United States
facility: Senior Adults Specialty Research (Sasr)
state: Texas
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: Milwaukee
country: United States
facility: Mcw Clinics At Froedtert Hospital
state: Wisconsin
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: London
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Greenfield Park
country: Canada
facility: Local Institution
state: Quebec
city: Copenhagen
country: Denmark
facility: Local Institution
city: Turku
country: Finland
facility: Local Institution
city: Toulouse
country: France
facility: Local Institution
state: Cedex 9
city: Bordeaux Cedex
country: France
facility: Local Institution
city: Dijon
country: France
facility: Local Institution
city: Nantes
country: France
facility: Local Institution
city: Rennes Cedex 9
country: France
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, 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.