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

• ClinicalTrials.gov Identifier: NCT00810147
• Recruitment Status: Completed
• First Posted: December 17, 2008
• Last Update Posted: October 12, 2015
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: December 16, 2008
• First Posted Date: December 17, 2008
• Last Update Posted Date: October 12, 2015
• Study Start Date: February 2009
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 30, 2009): Adverse Events [ Time Frame: 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) ]
• Original Primary Outcome Measures (submitted: December 16, 2008): Adverse Events [ Time Frame: Weekly for the 12-Week dosing period (Baseline-Week-12) and every 4 weeks during the 12-Week washout period (Weeks 16, 20, & 24) ]

Current Secondary Outcome Measures (submitted: April 30, 2009)

• Pharmacodynamics effects of Cerebral Spinal Fluid [ Time Frame: Baseline, Week 12 and Week 24 ]
• Pharmacodynamics effects of the Alzheimer's Disease Assessment Scale - Cognitive Subscale [ Time Frame: Baseline, Week 12, Week 24 and Week 36 ]
• Pharmacodynamics effects of the Alzheimer's Disease Collaborative Study - Activities of Daily Living scale [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 12 and Week 24 ]
• Characterize Pharmacodynamics/Pharmacokinetics effects in refining the Pharmacokinetics/Pharmacodynamics model with Phase 2 data [ Time Frame: Baseline, Week 12 and Week 24 ]
• Characterize Pharmacodynamics/Pharmacokinetics effects by exploring correlations between exposure, biomarkers, and clinical effects [ Time Frame: Baseline, Week 12 and Week 24 ]
• Characterize Pharmacodynamics/Pharmacokinetics effects by exploring Pharmacokinetics variability, including the correlation between polymorphisms of CYP enzymes [ Time Frame: Baseline, Week 12 and Week 24 ]

Original Secondary Outcome Measures (submitted: December 16, 2008)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase II, Multicenter, Double Blind, Placebo-Controlled Safety, Tolerability Study of BMS-708163 in Patients With Mild to Moderate 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 Mild to Moderate Alzheimer's Disease
• Brief Summary: 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
• 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: 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
• Drug: Placebo
  Capsules, Oral, 0 mg, once daily, 24 weeks

Study Arms

• Active Comparator: A1
  Intervention: Drug: BMS-708163
• Active Comparator: A2
  Intervention: Drug: BMS-708163
• Active Comparator: A3
  Intervention: Drug: BMS-708163
• Active Comparator: A4
  Intervention: Drug: BMS-708163
• Placebo Comparator: A5
  Intervention: Drug: Placebo

• 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 γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol. 2012 Nov;69(11):1430-40.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 14, 2010): 209
• Original Estimated Enrollment (submitted: December 16, 2008): 200
• Actual Study Completion Date: June 2010
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 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: Denmark, Finland, Sweden, United States

Administrative Information

• NCT Number: NCT00810147
• Other Study ID Numbers: CN156-013; EUDRACT: 2008-005929-11
• 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