title: Safety and pharmacokinetics of bapineuzumab in a single ascending-dose study in Japanese patients with mild to moderate Alzheimer's disease.
abstract: To evaluate the safety, tolerability and pharmacokinetic profile of bapineuzumab after a single intravenous injection in Japanese patients with mild to moderate Alzheimer's disease.
  
  
  
  Participants received either a placebo (n = 8), or bapineuzumab 0.15 (n = 6), 0.5 (n = 6), 1.0 (n = 6) or 2.0 (n = 6) mg/kg. Serum concentrations of bapineuzumab, antibapineuzumab antibody and total plasma β-amyloidx-40 were assayed.
  
  
  
  Adverse events for bapineuzumab and placebo groups were 71% and 88%, respectively. Treatment-emergent adverse events (cataract, injection site hemorrhage, nasopharyngitis, pneumonia and muscle twitching) reported for ≥2 participants were mild or moderate in severity and unrelated to bapineuzumab dose. No deaths, serious adverse events or withdrawals were reported. Mean peak concentration for bapineuzumab increased with dose, from 3.3 ± 0.9 μg/mL with the 0.15 mg/kg dose to 61.0 ± 32.8 μg/mL with 2.0 mg/kg. Mean bapineuzumab exposure (area under the curve from time 0 to last measurable concentration; μg·h/mL) increased in a linear manner with increasing dose (mean 1260 for 0.15 mg/kg, 4264 for 0.5 mg/kg, 7818 for 1.0 mg/kg, 15 313 for 2.0 mg/kg). Mean half-life ranged from 15 to 28 days, and clearance was similar across dose groups (range 0.12-0.17 mL/h/kg).
  
  
  
  Plasma β-amyloidx-40 levels increased with increasing doses of bapineuzumab. Bapineuzumab was safe and well tolerated at all doses in Japanese patients with mild to moderate Alzheimer's disease. Geriatr Gerontol Int 2016; 16: 644-650.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
authors.affiliation: Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umemura
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ichimiya
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Eizo
authors.initials: E
authors.lastname: Iseki
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Eto
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyakawa
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kirino
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Nobuto
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Baba
authors.affiliation: Development Japan, Pfizer Japan Inc., Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tsuchiwata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C545458:bapineuzumab
keywords: Alzheimer's disease; bapineuzumab; pharmacokinetics; phase 1; β-amyloid