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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00890890
Recruitment Status : Terminated
First Posted : April 30, 2009
Last Update Posted : October 12, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE April 29, 2009
First Posted Date  ICMJE April 30, 2009
Last Update Posted Date October 12, 2015
Study Start Date  ICMJE May 2009
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2013)
  • 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Avagacestat-treated patients will have a 24 week post treatment skin examination by a dermatologist ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2009)
Adverse Events [ Time Frame: During the treatment phase, every 2 weeks for the first 8 weeks, then monthly for the next 16weeks. Then every 8-weeks during the follow-up period (Weeks 28, 36, & 52) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2012)
Predictive value of Cerebral Spinal Fluid (CSF) biomarkers (Aβ40, and Aβ42, total Tau, total Tau/Aβ42 ratio, phosphorylated Tau) on progression to dementia [ Time Frame: Baseline (Week 0), Week 2 (optional), Week 24 and Week 104 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2009)
  • To assess the predictive value and longitudinal behavior of CSF biomarkers (Aβ40,Aβ42, total Tau, phosphorylated Tau) and volumetric MRI [ Time Frame: Biomarkers will be assessed at Baseline, Week 24 and Week 52 ]
  • Prospectively characterize effects on the following assessments as part of the natural course (in placebo patients) & potential impact of BMS-708163. Assess drug effects on progression to dementia (based on confirmed progression using DSM-IV criteria) [ Time Frame: Progression to dementia will be assessed on an ongoing basis at all scheduled visits ]
  • Global clinical impression as assessed with the Clinical Dementia Rating-Sum of Boxes (CDR-SB), an instrument designed to measure the severity of cognitive symptoms in daily life [ Time Frame: CDR-SB will be assessed at baseline, week 12, week 24, week 36 & week 52 ]
  • To assess Notch-mediated (safety related) effects of BMS-708163 [ Time Frame: Notch-mediated safety assessments will be done at every visit ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multicenter, Double Blind, Placebo-Controlled, Safety and Tolerability Study of BMS-708163 in Patients With Prodromal Alzheimer's Disease
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: Avagacestat
    Capsules, Oral, 50 mg, once daily, 104 - 220 Weeks
    Other Name: BMS-708163
  • Drug: Placebo
    Capsules, Oral, 0 mg, once daily, 104 - 220 Weeks
Study Arms  ICMJE
  • Experimental: Avagacestat (50 mg)
    Intervention: Drug: Avagacestat
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 4, 2013)
263
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2009)
270
Actual Study Completion Date  ICMJE July 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Denmark,   Finland,   France,   Sweden,   United States
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT00890890
Other Study ID Numbers  ICMJE CN156-018
2009-010067-16 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP