Safety, Tolerability, and Pharmacokinetics of Donanemab in Healthy Chinese Participants: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles, is the leading cause of dementia globally. Donanemab is a humanized immunoglobulin G1 in development as a treatment to slow AD progression. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PKs), and immunogenicity of donanemab in healthy Chinese adults. The study included screening, inpatient, and follow-up periods. Following successful screening, participants were assigned to one of three donanemab cohorts (350, 700, or 1400 mg) and randomized in a 5:1 ratio to receive donanemab or placebo. Participants received a single intravenous (IV) dose of donanemab or placebo, and the safety, PKs, and immunogenicity of donanemab were monitored. A total of 36 male Chinese participants were included. All treatment-emergent adverse events (TEAEs) were mild in severity. Two participants on 350 mg donanemab experienced treatment-related TEAEs. Serum concentrations decreased over time with dose-dependent PK parameters (C, t, AUC, and AUC) as expected. Clearance values were similar across doses. All donanemab recipients developed treatment-emergent antidrug antibodies (ADAs) in the inpatient and follow-up periods, with similar ADA titer ranges across all donanemab doses. Single IV doses of donanemab 350, 700, and 1400 mg showed acceptable safety, tolerability, and dose-proportional PK in healthy Chinese adults.