A Randomized Phase 1 Pharmacokinetic Study Comparing the Potential Biosimilar LRG201902 With Liraglutide (Victoza®) in Healthy Male Subjects

• Published in: Frontiers in pharmacology Vol. 11; p. 610880
• Main Authors: Mai, Gang, Fan, Lianlian, Li, Mupeng, Zhang, Peiwen, Gan, Chunyan, Huang, Qian, Shentu, Jianzhong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 29.01.2021
• Subjects: bioequivalence; biosimilar; liraglutide; pharmacokinetics; Pharmacology; safety; liraglutide; pharmacokinetics; safety; bioequivalence; biosimilar
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2020.610880

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 AUC 0–t , AUC 0–∞ , and C max . Pharmacokinetic similarity was achieved if 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUC0-t, AUC 0–∞ , and C max were within the range of 80–125%. Other pharmacokinetic parameters including T max , t ½ , and λ z were also measured. Safety profile and immunogenicity data were collected from each subject. Results: C max , AUC 0–t , and AUC 0–∞ were similar between the two groups. GMRs of Cmax, AUC 0–t , and AUC 0–∞ were 113.50%, 107.21%, and 106.97% between LRG201902 and Victoza ® respectively. The 90% CIs for the GMRs of C max , AUC 0-t , and AUC 0–∞ were all within the PK equivalence criteria. Mean serum concentration-time profiles, secondary pharmacokinetic parameters (T max , t ½ , and λ z ) 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.