Gang Mai1, Lianlian Fan1, Mupeng Li1, Peiwen Zhang1, Chunyan Gan1, Qian Huang1, Jianzhong Shentu1,2. 1. Phase 1 Clinical Trial Center, People's Hospital of Deyang City, Deyang, China. 2. Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract
Objective: Pharmacokinetic (PK) similarity between biosimilar candidate LRG201902 and European Union-sourced liraglutide reference product (Victoza®) was evaluated. Safety and immunogenicity were also assessed. Methods: This single-dose, randomized, open-label, 2-period crossover study (CTR20192342) was conducted in thirty-eight healthy adult male subjects. Volunteers were randomized 1:1 at the beginning to receive a single 0.6 mg dose of Victoza® or LRG201902 by subcutaneous injection during the first period. Following 8 days washout period, all subjects received the alternate formulation during the second period. Blood samples were collected up to 72 h after administration. The primary pharmacokinetic endpoints were AUC0-t, AUC0-∞, and Cmax. Pharmacokinetic similarity was achieved if 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUC0-t, AUC0-∞, and Cmax were within the range of 80-125%. Other pharmacokinetic parameters including Tmax, t½, and λz were also measured. Safety profile and immunogenicity data were collected from each subject. Results:Cmax, AUC0-t, and AUC0-∞ were similar between the two groups. GMRs of Cmax, AUC0-t, and AUC0-∞ were 113.50%, 107.21%, and 106.97% between LRG201902 and Victoza® respectively. The 90% CIs for the GMRs of Cmax, AUC0-t, and AUC0-∞ were all within the PK equivalence criteria. Mean serum concentration-time profiles, secondary pharmacokinetic parameters (Tmax, t½, and λz) were comparable between groups. Treatment-related adverse events were reported by 27.8% and 23.7% subjects in the LRG201902 and Victoza® arms, respectively. All post-dose samples were detected negative for anti-drug antibodies. Conclusion: This study demonstrates pharmacokinetic similarity of LRG201902 to Victoza® in healthy subjects. The safety and immunogenicity profiles were similar for the two products.
RCT Entities:
Objective: Pharmacokinetic (PK) similarity between biosimilar candidate LRG201902 and European Union-sourced liraglutide reference product (Victoza®) was evaluated. Safety and immunogenicity were also assessed. Methods: This single-dose, randomized, open-label, 2-period crossover study (CTR20192342) was conducted in thirty-eight healthy adult male subjects. Volunteers were randomized 1:1 at the beginning to receive a single 0.6 mg dose of Victoza® or LRG201902 by subcutaneous injection during the first period. Following 8 days washout period, all subjects received the alternate formulation during the second period. Blood samples were collected up to 72 h after administration. The primary pharmacokinetic endpoints were AUC0-t, AUC0-∞, and Cmax. Pharmacokinetic similarity was achieved if 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUC0-t, AUC0-∞, and Cmax were within the range of 80-125%. Other pharmacokinetic parameters including Tmax, t½, and λz were also measured. Safety profile and immunogenicity data were collected from each subject. Results: Cmax, AUC0-t, and AUC0-∞ were similar between the two groups. GMRs of Cmax, AUC0-t, and AUC0-∞ were 113.50%, 107.21%, and 106.97% between LRG201902 and Victoza® respectively. The 90% CIs for the GMRs of Cmax, AUC0-t, and AUC0-∞ were all within the PK equivalence criteria. Mean serum concentration-time profiles, secondary pharmacokinetic parameters (Tmax, t½, and λz) were comparable between groups. Treatment-related adverse events were reported by 27.8% and 23.7% subjects in the LRG201902 and Victoza® arms, respectively. All post-dose samples were detected negative for anti-drug antibodies. Conclusion: This study demonstrates pharmacokinetic similarity of LRG201902 to Victoza® in healthy subjects. The safety and immunogenicity profiles were similar for the two products.
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