Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alirocumab in Healthy Chinese Subjects: A Randomized, Do
- PDF / 3,841,573 Bytes
- 15 Pages / 595.276 x 790.866 pts Page_size
- 24 Downloads / 210 Views
ORIGINAL RESEARCH ARTICLE
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alirocumab in Healthy Chinese Subjects: A Randomized, Double‑Blind, Placebo‑Controlled, Ascending Single‑Dose Study Haiyan Li1,2 · Yudong Wei2 · Zhenhua Yang2 · Shuang Zhang2 · Xiuxiu Xu2 · Mengmeng Shuai3 · Olivier Vitse4 · Yiwen Wu3 · Marie T. Baccara‑Dinet4 · Yi Zhang5 · Jianyong Li6
© The Author(s) 2020
Abstract Background The addition of alirocumab (a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 [PCSK9]) to background statin therapy provides significant incremental low-density lipoprotein cholesterol (LDL-C) lowering and cardiovascular event risk reduction. Objectives Our objectives were to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of alirocumab in healthy Chinese subjects. Methods In this double-blind, placebo-controlled, phase I study, 35 Chinese subjects (aged 21–45 years) with baseline LDL-C > 100 mg/dL (2.59 mmol/L) were randomized to receive a single 1 mL subcutaneous injection of alirocumab 75, 150, or 300 mg, or placebo, and followed up for ~ 12 weeks. Results Treatment-emergent adverse events, most frequently nasal congestion and dry throat, were reported in three of seven or eight subjects in each alirocumab dose group (two of seven in the placebo group). One patient receiving alirocumab 300 mg had a mild local injection-site reaction. No alirocumab recipients demonstrated antidrug antibodies. Maximum alirocumab serum concentrations (6–34 mg/dL) occurred at a median of 3–7 days across the dose groups. Maximum mean LDL-C reductions from baseline were observed on days 8, 15, and 22 with alirocumab 75 (55.3%), 150 (63.7%), and 300 mg (73.7%), respectively. Mean free PCSK9 levels were reduced to below the lower limit of quantification within 4 h of dosing. Total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B were reduced with alirocumab. Conclusions In Chinese subjects, alirocumab 75, 150, and 300 mg was safe and well-tolerated. Pharmacokinetic/pharmacodynamic parameters, including clinically meaningful reductions in LDL-C and other lipids/lipoproteins, were consistent with data from Japanese and Western populations. Clinicaltrials.gov identifier: NCT02979015.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40256-020-00394-1) contains supplementary material, which is available to authorized users. * Haiyan Li [email protected] Extended author information available on the last page of the article Vol.:(0123456789)
H. Li et al.
Key Points Data regarding the safety, tolerability, and pharmacokinetic and pharmacodynamic parameters of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab in Chinese subjects are limited. In this double-blind, placebo-controlled, phase I study in 35 healthy Chinese subjects, alirocumab administered as a single ascending subcutaneous dose of 75, 150, or 300 mg was generally
Data Loading...
