Qi Shen1, Ying Jin1, Xiangjie Di1, Chao Hu1, Runhan Liu1, Ying Wang1, Xiaohui Qi1, Yongsheng Wang1, Zhenlei Wang2. 1. Clinical Trial Center/NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, West China Hospital of Sichuan University, No.5 Telecom Road, Wuhou District, Chengdu, 610041, China. 2. Clinical Trial Center/NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, West China Hospital of Sichuan University, No.5 Telecom Road, Wuhou District, Chengdu, 610041, China. wangzhenlei@wchscu.cn.
Abstract
BACKGROUND AND OBJECTIVE: Erenumab is the first-in-class, selective, and competitive human monoclonal antibody antagonist of the calcitonin gene-related peptide (CGRP) receptor that has been shown to be effective and well-tolerated in the preventive therapy of episodic and chronic migraine. The pharmacokinetics of erenumab may be affected by differences in race and ethnicity, which can lead to suboptimal outcomes. The present study was conducted to assess the single-dose pharmacokinetics and safety of erenumab in healthy Chinese subjects. METHODS: This was an open-label, randomized, parallel group, non-confirmatory, single-dose study in healthy Chinese subjects. A total of 24 healthy Chinese subjects of both sexes aged between 14 and 45 years were administered a single subcutaneous injection of erenumab 70 mg or 140 mg. The serum concentration of erenumab was quantified using a validated enzyme-linked immunosorbent assay method and pharmacokinetic parameters were determined using non-compartmental models. Safety was also assessed. RESULTS: A total of 55 subjects were screened for eligibility and 25 subjects were randomized to receive study treatments (12 subjects to the 70-mg erenumab group and 13 subjects to the 140-mg erenumab group). Erenumab was absorbed slowly with maximum serum concentration (Cmax) occurring 3-11 days after administration. The mean Cmax and area under the serum concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase (AUC0-∞) were 9.20 µg/mL and 296 day·µg/mL for the 70 mg dose group, and 15.6 µg/mL and 569 day·µg/mL for the 140 mg dose group, respectively. Serum concentrations of erenumab exhibited low to high variability, with variable coefficients ranging from 17.1 to 72.2% for the 70-mg dose and 32.5 to 88.5% for the 140-mg dose. All adverse events were mild or moderate in intensity, and all resolved without intervention. CONCLUSIONS: Erenumab was safe and well tolerated after a single subcutaneous injection in healthy Chinese subjects. The systemic exposure in Chinese subjects in terms of AUC0-∞ was 70% higher than that in White subjects as previously reported. CHINESE CLINICAL TRIAL REGISTRY NO: ChiCTR2000032435.
BACKGROUND AND OBJECTIVE: Erenumab is the first-in-class, selective, and competitive human monoclonal antibody antagonist of the calcitonin gene-related peptide (CGRP) receptor that has been shown to be effective and well-tolerated in the preventive therapy of episodic and chronic migraine. The pharmacokinetics of erenumab may be affected by differences in race and ethnicity, which can lead to suboptimal outcomes. The present study was conducted to assess the single-dose pharmacokinetics and safety of erenumab in healthy Chinese subjects. METHODS: This was an open-label, randomized, parallel group, non-confirmatory, single-dose study in healthy Chinese subjects. A total of 24 healthy Chinese subjects of both sexes aged between 14 and 45 years were administered a single subcutaneous injection of erenumab 70 mg or 140 mg. The serum concentration of erenumab was quantified using a validated enzyme-linked immunosorbent assay method and pharmacokinetic parameters were determined using non-compartmental models. Safety was also assessed. RESULTS: A total of 55 subjects were screened for eligibility and 25 subjects were randomized to receive study treatments (12 subjects to the 70-mg erenumab group and 13 subjects to the 140-mg erenumab group). Erenumab was absorbed slowly with maximum serum concentration (Cmax) occurring 3-11 days after administration. The mean Cmax and area under the serum concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase (AUC0-∞) were 9.20 µg/mL and 296 day·µg/mL for the 70 mg dose group, and 15.6 µg/mL and 569 day·µg/mL for the 140 mg dose group, respectively. Serum concentrations of erenumab exhibited low to high variability, with variable coefficients ranging from 17.1 to 72.2% for the 70-mg dose and 32.5 to 88.5% for the 140-mg dose. All adverse events were mild or moderate in intensity, and all resolved without intervention. CONCLUSIONS: Erenumab was safe and well tolerated after a single subcutaneous injection in healthy Chinese subjects. The systemic exposure in Chinese subjects in terms of AUC0-∞ was 70% higher than that in White subjects as previously reported. CHINESE CLINICAL TRIAL REGISTRY NO: ChiCTR2000032435.