Original ArticlesA Single Ascending Dose Study of Bapineuzumab in Patients With Alzheimer DiseaseBlack, Ronald S. MD*; Sperling, Reisa A. MD†; Safirstein, Beth MD‡; Motter, Ruth N. MPH§; Pallay, Allan MS*; Nichols, Alice PhD*; Grundman, Michael MD, MPH§ Author Information *Wyeth Research, Collegeville, PA †Brigham and Women's Hospital, Harvard Medical School, Boston, MA ‡MD Clinical, Hallandale Beach, FL §Elan Pharmaceuticals, South San Francisco, CA Sponsored by Wyeth Pharmaceuticals (Collegeville, PA) and Elan Pharmaceuticals (San Francisco, CA). Reprints: Ronald S. Black, MD, Wyeth Research, 500 Arcola Road, Collegeville 19426, PA (e-mail: [email protected]). Received for publication June 8, 2009 accepted October 2, 2009 Disclosures: Ronald S. Black, Allan Pallay, and Alice Nichols are employees of Wyeth Pharmaceuticals. Reisa A. Sperling has received grants from Wyeth and Elan for research activities, and honoraria for consulting services. Ruth N. Motter and Michael Grundman are employees of Elan Pharmaceuticals. The remaining authors have no disclosures. Alzheimer Disease & Associated Disorders 24(2):p 198-203, April 2010. | DOI: 10.1097/WAD.0b013e3181c53b00 Buy Metrics Abstract The safety, tolerability, and pharmacokinetics (PKs) of bapineuzumab (AAB–001), a humanized monoclonal antibody to amyloid β, 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 β 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. © 2010 Lippincott Williams & Wilkins, Inc.