Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Drug: BMS-241027Drug: Placebo matching BMS-241027
- Registration Number
- NCT01492374
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of the study is to evaluate safety and the pharmacodynamic effects of BMS-241027 on cerebrospinal fluid (CSF) Tau, connectivity magnetic resonance imaging (MRI), and computerized cognitive tests in mild Alzheimer's disease (AD) subjects, following 9 weekly intravenous (IV) infusions of BMS-241027
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- Mild AD Subjects meeting National Institute of Neurological Disorders and Stroke - Alzheimer's Disease Related Disorders Association(NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders-Forth Edition, Text Revision (DSM-IV-TR) criteria
- Mini-Mental State Exam (MMSE) Score between 20 & 26 (inclusive)
- CSF consistent with AD pathology
- Screening brain MRI - normal - commensurate with age or demonstrate atrophy consistent with AD diagnosis (dx); reveal no more than mild white matter disease; up to 2 lacunar infarcts acceptable except in anterior thalamus, genu of internal capsule or basal forebrain; reveal no cortical infarcts; reveal no more than 4 microbleeds; reveal no focal asymmetric lobar atrophy or other findings suggesting primary cause of dementia is attributed to a cause other than AD; reveal no macrohemorrhages (>10 mm)
- Subjects must have reliable study partners
- Men and Women of Non Child Bearing Potentia (WONCBP), ages 50-90 years
- Subjects with any other medical condition other than mild AD that could explain subjects' memory or cognitive deficits
- Subjects diagnosed with moderate or severe AD per DSM-IV criteria
- Subjects with a history (hx) of stroke
- Subjects with a hx of GI illnesses
- Subjects with Vitamin B12 or folate deficiency
- Subjects with any unstable cardiovascular (CV), pulmonary, Gastrointestinal (GI) or hepatic disease within 30 days prior to screening
- Subjects with active liver dx or history of hepatic intolerance
- Subjects with a Geriatric Depression Scale score of ≥ 6 at screening
- Subjects treated for or have had a diagnosis of schizophrenia
- Subjects treated for or have had a diagnosis of bipolar disease within 3 years prior to screening
- Subjects with a history of generalized peripheral neuropathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: BMS-241027 (0.003 mg/kg) BMS-241027 - Arm 4: Placebo matching BMS-241027 Placebo matching BMS-241027 - Arm 2: BMS-241027 (0.01 mg/kg) BMS-241027 - Arm 3: BMS-241027 (0.03 mg/kg) BMS-241027 -
- Primary Outcome Measures
Name Time Method Safety assessments: based on frequency of Serious Adverse Events (SAEs), frequency of Adverse events (AEs), discontinuation due to AEs and dose reduction Within the first 70 day after first dose Biomarker Measures: CSF levels of Tau N-terminal domain fragments Within the first 70 day after first dose
- Secondary Outcome Measures
Name Time Method Effects of BMS-241027 on connectivity MRI Within the first 70 days after first dose Effects of BMS-241027 on CSF levels of neurofilaments Within the first 70 days after first dose Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment Within the first 70 days after first dose Effects of BMS-241027 on cognitive performance using computerized cognitive tests Weeks 3, 6 and 9 Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's disease Weeks 1, 4, and 9 Intensive pharmacokinetic parameter C24 will be derived from subgroups of subjects at Week 7
Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease Weeks 1, 4, and 9 Intensive pharmacokinetic parameter Cmax will be derived from subgroups of subjects at Week 7
Time of maximal observed plasma concentration (Tmax) of BMS-241027 in subjects with mild Alzheimer's disease Weeks 1, 4, and 9 Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7
Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests Within the first 70 day after first dose Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease Weeks 1, 4, and 9 Intensive pharmacokinetic parameter AUC(TAU) will be derived from subgroups of subjects at Week 7
Trial Locations
- Locations (15)
Associated Neurologists Of Southern Connecticut, P.C.
🇺🇸Fairfield, Connecticut, United States
Palm Beach Neurological Center Advanced Research Consultants
🇺🇸Palm Beach Gardens, Florida, United States
Compass Research, Llc
🇺🇸Orlando, Florida, United States
Michigan State University
🇺🇸East Lansing, Michigan, United States
Local Institution
🇸🇪Stockholm, Sweden
Anaheim Clinical Trials Llc
🇺🇸Anaheim, California, United States
Ucsf Memory And Aging Center
🇺🇸San Francisco, California, United States
Brigham And Women'S Hospital
🇺🇸Boston, Massachusetts, United States
Hospital Of The University Of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Penn Memory Center
🇺🇸Philadelphia, Pennsylvania, United States
Lifetree Clinical Research
🇺🇸Salt Lake City, Utah, United States
Alexian Brothers Neurosciences Institute Clinical Research
🇺🇸Elk Grove Village, Illinois, United States
The Clinical Trial Center, Llc
🇺🇸Jenkintown, Pennsylvania, United States
Alpine Clinical Research Center, Inc.
🇺🇸Boulder, Colorado, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States