AUTHOR=Mai Gang , Fan Lianlian , Li Mupeng , Zhang Peiwen , Gan Chunyan , Huang Qian , Shentu Jianzhong 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.610880

DOI=10.3389/fphar.2020.610880

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> Pharmacokinetic (PK) similarity between biosimilar candidate LRG201902 and European Union-sourced liraglutide reference product (Victoza<sup>®</sup>) was evaluated. Safety and immunogenicity were also assessed.</p><p><bold>Methods:</bold> 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<sup>®</sup> 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<sub>0–t</sub>, AUC<sub>0–∞</sub>, and C<sub>max</sub>. Pharmacokinetic similarity was achieved if 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUC0-t, AUC<sub>0–∞</sub>, and C<sub>max</sub> were within the range of 80–125%. Other pharmacokinetic parameters including T<sub>max</sub>, t<sub>½</sub>, and λ<sub>z</sub> were also measured. Safety profile and immunogenicity data were collected from each subject.</p><p><bold>Results:</bold> C<sub>max</sub>, AUC<sub>0–t</sub>, and AUC<sub>0–∞</sub> were similar between the two groups. GMRs of Cmax, AUC<sub>0–t</sub>, and AUC<sub>0–∞</sub> were 113.50%, 107.21%, and 106.97% between LRG201902 and Victoza<sup>®</sup> respectively. The 90% CIs for the GMRs of C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0–∞</sub> were all within the PK equivalence criteria. Mean serum concentration-time profiles, secondary pharmacokinetic parameters (T<sub>max</sub>, t<sub>½</sub>, and λ<sub>z</sub>) were comparable between groups. Treatment-related adverse events were reported by 27.8% and 23.7% subjects in the LRG201902 and Victoza<sup>®</sup> arms, respectively. All post-dose samples were detected negative for anti-drug antibodies.</p><p><bold>Conclusion:</bold> This study demonstrates pharmacokinetic similarity of LRG201902 to Victoza<sup>®</sup> in healthy subjects. The safety and immunogenicity profiles were similar for the two products.</p>