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

• ClinicalTrials.gov Identifier: NCT00890890
• Recruitment Status: Terminated
• First Posted: April 30, 2009
• Last Update Posted: October 12, 2015
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: April 29, 2009
• First Posted Date: April 30, 2009
• Last Update Posted Date: October 12, 2015
• Study Start Date: May 2009
• Actual Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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) ]
• Current Secondary Outcome Measures (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 (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: 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
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 4, 2013): 263
• Original Estimated Enrollment (submitted: April 29, 2009): 270
• Actual Study Completion Date: July 2013
• Actual Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Denmark, Finland, France, Sweden, United States
• Removed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT00890890
• Other Study ID Numbers: CN156-018; 2009-010067-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bristol-Myers Squibb
• Study Sponsor: Bristol-Myers Squibb
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: September 2015