Study Evaluating The Safety Of AAB-003 (PF-05236812) In Subjects With Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Drug: AAB-003 (PF-05236812)Other: Placebo
- Registration Number
- NCT01193608
- Lead Sponsor
- Pfizer
- Brief Summary
This is a study to evaluate the safety of multiple doses of AAB-003 (PF-05236812) in patients with mild to moderate Alzheimer's Disease. Patients will receive either AAB-003 (PF-05236812) or placebo. Each patient's participation will last approximately 41 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 88
- Diagnosis of probable Alzheimer's Disease with MMSE score of 16-26, and brain MRI consistent with the diagnosis of Alzheimer's Disease
- Concurrent use of cholinesterase inhibitor or memantine allowed, if stable.
- Caregiver will participate and be able to attend clinic visits with patient
- Significant neurological disease other than Alzheimer's Disease
- Major psychiatric disorder
- Contraindication to undergo brain MRI (e.g., pacemaker, CSF shunt, or foreign metal objects in the body)
- Women of childbearing potential
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 1 mg/kg AAB-003 AAB-003 (PF-05236812) - 0.5 mg/kg AAB-003 AAB-003 (PF-05236812) - 2 mg/kg AAB-003 AAB-003 (PF-05236812) - 4 mg/kg AAB-003 AAB-003 (PF-05236812) - 8 mg/kg AAB-003 AAB-003 (PF-05236812) - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Number of Participants With Laboratory Abnormalities Baseline up to 39 Weeks and at Early Withdrawal Number of Participants With Vital Signs of Potential Clinical Concern Baseline up to 39 Weeks and at Early Withdrawal Criteria for potential clinical concern in vital signs included: supine/sitting pulse rate of less than (\<) 40 or more than (\>) 120 beats per minute (bpm), and standing pulse rate of \<40 or \>140 bpm; systolic blood pressure (SBP) of more than or equal to (\>=)30 millimeters of mercury (mm Hg) change from baseline in same posture and \<90 mm Hg; diastolic blood pressure (DBP) \>=20 mm Hg change from baseline in same posture and \<50 mm Hg. Only supine vital signs were planned for this study. Unplanned sitting vital signs were collected only in the 8/mg and placebo groups and also reported.
Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Baseline up to 39 Weeks and at Early Withdrawal Number of Participants With Abnormal Neurological Examination Findings Screening, Day 1 (Baseline) and Weeks 1,6,13,19,26,32, and 39, and at Early Withdrawal The neurological examination was done to the extent needed to assess the participant for any potential changes in neurological status, as determined by the investigator. The minimum items assessed were level of consciousness, speech, cranial nerves, motor, sensory, coordination, gait, and tendon reflexes.
Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. Serum Decay Half-Life (t1/2) for AAB-003 at Week 26 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Baseline up to Week 39 or Early Withdrawal The C-SSRS assessed whether the participant experienced the following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").
Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding Baseline up to Week 32. Brain MRIs were collected during the course of study to assess for any potential drug-related changes that might have constituted a safety concern for study participants. Findings suggestive of either vasogenic edema (VE) or intracranial hemorrhage represented adverse events of special circumstance and were to be reported immediately.
Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit Day 1, Week 13, and Week 26 VE of the brain, identified via MRI, was identified as an adverse event of special circumstance.
Number of Participants With Abnormal Physical Examination Findings Baseline up to 39 Weeks and at Early Withdrawal Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. Systemic Clearance (CL) for AAB-003 in Serum at Day 1 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. Systemic Clearance (CL) for AAB-003 in Serum at Week 26 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. Serum Decay Half-Life (t1/2) for AAB-003 at Day 1 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. Average Concentration (Cavg) for AAB-003 in Serum at Day 1 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. Average Concentration (Cavg) for AAB-003 in Serum at Week 26 Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria Baseline, Weeks 1,13,16,26,39 or Early Withdrawal Criteria for ECG values of potential clinical concern are: interval between the start of the ECG P wave and the start of the QRS complex corresponding to the time between onset of atrial depolarization and onset of ventricular depolarization (PR): \>= 300 milliseconds (msec), and \>=25% increase when baseline \>=200 msec/ \>=50% increase when baseline less than or equal to (\<=) 200 msec; time from ECG Q wave to the end of S wave corresponding to ventricular depolarization (QRS): \>=200 msec, and \>=25% increase when baseline \>100 msec/ \>=50% increase when baseline \<=100 msec; QTc using Fridericia's formula (QTcF) interval: 450 to \<480 msec, \>=480 msec; QTcF change from baseline: 30 to \<60 msec, and \>=60 msec.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (29)
Atlanta Center for Medical Research
🇺🇸Atlanta, Georgia, United States
Belmont Center for Comprehensive Treatment
🇺🇸Philadelphia, Pennsylvania, United States
Foers Medical Arts Pharmacy
🇺🇸Bethesda, Maryland, United States
CBH Health, LLC
🇺🇸Rockville, Maryland, United States
Early Phase Investigational Center
🇺🇸Escondido, California, United States
Franck's Pharmacy
🇺🇸Ocala, Florida, United States
Munroe Regional Medical Center
🇺🇸Ocala, Florida, United States
Synergy Clinical Research Center of Escondido
🇺🇸Escondido, California, United States
Konkuk University Medical Center, Department of Neurology
🇰🇷Seoul, Korea, Republic of
Renstar Medical Research
🇺🇸Ocala, Florida, United States
DePaul Health Center
🇺🇸St. Louis, Missouri, United States
Advanced Imaging of Ocala
🇺🇸Ocala, Florida, United States
Precise Research Centers
🇺🇸Flowood, Mississippi, United States
Marty's Pharmacy
🇺🇸Flowood, Mississippi, United States
Samsung Medical Center, Department of Neurology
🇰🇷Seoul, Korea, Republic of
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Central Jersey Radiology
🇺🇸Oakhurst, New Jersey, United States
Borgess Research Institute
🇺🇸Kalamazoo, Michigan, United States
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Millennium Psychiatric Associates, LLC
🇺🇸Creve Coeur, Missouri, United States
KNI/Southwest Michigan Imaging Center, LLC
🇺🇸Kalamazoo, Michigan, United States
Albert Einstein Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Pharmacare USA
🇺🇸Edison, New Jersey, United States
ASAN Medical Center
🇰🇷Seoul, Korea, Republic of
Inha University Hospital, Department of Neurology
🇰🇷Incheon, Korea, Republic of
Memory Enhancement Center of America, Inc.
🇺🇸Eatontown, New Jersey, United States
MD Clinical
🇺🇸Hallandale Beach, Florida, United States
Seoul National University Bundang Hospital, Department of Neurology
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Brentwood Behavioral Healthcare
🇺🇸Flowood, Mississippi, United States