A single ascending dose study of bapineuzumab in patients with Alzheimer disease.
The safety, tolerability, and pharmacokinetics (PKs) of bapineuzumab (AAB-001), a humanized monoclonal antibody to amyloid beta, were evaluated in patients with mild-to-moderate Alzheimer disease in a phase 1, randomized, third-party unblinded, placebo-controlled, single ascending dose trial. Thirty patients received bapineuzumab infusion of 0.5, 1.5, or 5 mg/kg or placebo (6 active, 2 placebo for 0.5 and 1.5-mg/kg cohorts; 10 active, 4 placebo for 5.0-mg/kg cohort). Three patients in the highest dose cohort (5.0 mg/kg) developed magnetic resonance imaging abnormalities consistent with vasogenic edema, predominantly high signal abnormalities on fluid-attenuated inversion recovery sequences, all of which resolved over time. Plasma amyloid beta was elevated from baseline, peaking approximately 24 hours after infusion. PK analysis demonstrated a half-life of 21 to 26 days, supporting a 13-week dosing interval for bapineuzumab. This small, single-dose study demonstrated the safety profile and PK characteristics of bapineuzumab and was used to design later safety and efficacy trials.
Black
Ronald S
RS
Wyeth Research, Collegeville, PA 19426, USA. blackr@wyeth.com
Sperling
Reisa A
RA
Safirstein
Beth
B
Motter
Ruth N
RN
Pallay
Allan
A
Nichols
Alice
A
Grundman
Michael
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000009:adverse effects
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018697:Nootropic Agents; C545458:bapineuzumab