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Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01492374
First received: December 13, 2011
Last updated: July 23, 2014
Last verified: October 2013

December 13, 2011
July 23, 2014
February 2012
October 2013   (final data collection date for primary outcome measure)
  • Safety assessments: based on frequency of Serious Adverse Events (SAEs), frequency of Adverse events (AEs), discontinuation due to AEs and dose reduction [ Time Frame: Within the first 70 day after first dose ] [ Designated as safety issue: Yes ]
  • Biomarker Measures: CSF levels of Tau N-terminal domain fragments [ Time Frame: Within the first 70 day after first dose ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01492374 on ClinicalTrials.gov Archive Site
  • Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
  • Effects of BMS-241027 on cognitive performance using computerized cognitive tests [ Time Frame: Weeks 3, 6 and 9 ] [ Designated as safety issue: No ]
  • Effects of BMS-241027 on connectivity MRI [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
  • Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter Cmax will be derived from subgroups of subjects at Week 7
  • Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter C24 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 [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter AUC(TAU) will be derived from subgroups of subjects at Week 7
  • Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests [ Time Frame: Within the first 70 day after first dose ] [ Designated as safety issue: Yes ]
  • Effects of BMS-241027 on CSF levels of neurofilaments [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
  • Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
  • Effects of BMS-241027 on cognitive performance using computerized cognitive tests [ Time Frame: Weeks 3, 6 and 9 ] [ Designated as safety issue: No ]
  • Effects of BMS-241027 on connectivity MRI [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
  • Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter Cmax will be derived from subgroups of subjects at Week 7
  • Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter C24 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 [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter AUC(TAU) will be derived from subgroups of subjects at Week 7
  • Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests [ Time Frame: Within the first 70 day after first dose ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease
A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease

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

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Alzheimer's Disease
  • Drug: BMS-241027
    Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks
  • Drug: BMS-241027
    Intravenous (IV), 0.01 mg/kg, Once Weekly, 9 weeks
  • Drug: BMS-241027
    Intravenous (IV), 0.03 mg/kg, Once Weekly, 9 weeks
  • Drug: Placebo matching BMS-241027
    Intravenous (IV), 0.0 mg/kg, Once Weekly, 9 weeks
  • Experimental: Arm 1: BMS-241027 (0.003 mg/kg)
    Intervention: Drug: BMS-241027
  • Experimental: Arm 2: BMS-241027 (0.01 mg/kg)
    Intervention: Drug: BMS-241027
  • Experimental: Arm 3: BMS-241027 (0.03 mg/kg)
    Intervention: Drug: BMS-241027
  • Experimental: Arm 4: Placebo matching BMS-241027
    Intervention: Drug: Placebo matching BMS-241027
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
October 2013
October 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Both
50 Years to 90 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   France,   Germany,   Sweden
 
NCT01492374
CN167-003, 2011-004065-33
Yes
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
October 2013

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