A Single‐dose, Two‐Period Crossover Bioequivalence Study Comparing Two Liraglutide Formulations in Healthy Chinese Subjects. Issue 4 (17th January 2023)

• Record Type: Journal Article
• Authors: Feng, Shiyin; Cai, Linrui; Wang, Xiaoyan; Yu, Qin; Cai, Junjie; Hao, Wenjing; Chen, Zhuo; Su, Xu; Du, Chunfeng; Zou, Qin; Guo, Weiyi; Du, Dan; Hu, Feng; Li, Fengshan; Liu, Yan
• Is Part Of: Clinical pharmacology in drug development. Volume 12:Issue 4(2023)
• Page Start: 385
• Page End: 391
• Publication Date: 2023-01-17
• Subjects: bioequivalence -- GLP‐1 -- LC‒MS/MS -- liraglutide -- type 2 diabetes; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.1187
• Languages: English
• ISSNs: 2160-7648

Abstract

Abstract: Liraglutide, a glucagon‐like peptide 1 receptor agonist, is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. The original liraglutide products are costly, which limits patient access to this therapeutic treatment. Herein, a biosimilar was developed that is highly similar to the reference drug in molecular structure and bioactivity, and is expected to have similar pharmacokinetic (PK) and safety profiles in clinical studies. This study aimed to primarily evaluate the bioequivalence of 2 liraglutide formulations and secondarily assess their safety in healthy Chinese subjects following a single‐dose subcutaneous injection. Thirty‐two healthy volunteers were recruited in this randomized, open‐label, single‐dose, 2‐period crossover bioequivalence study (ChiCTR2100043348). The geometric mean ratios (GMRs) of the test drug to the reference drug (T/R) and corresponding 90% confidence intervals (CIs) for maximum concentration (Cmax ) and the area under the concentration–time curve from time 0 to the time of the last quantifiable concentration (AUC0–t ) were estimated using a mixed‐effects model, and bioequivalence was determined to have been achieved if the 2‐sided 90%CI fell within the predefined range of 80%–125%. PK parameters were comparable between T and R, with GMRs of T/R for Cmax and AUC0–t being 105.7% and 107.7%, respectively, the 90%CI of which met the acceptance criteria for bioequivalence. We also observed a similar and favorable safety profile in the T and R arms, with adverse events being predominantly mild in severity and of gastrointestinal origin. Our findings indicate that the test drug is safe and well tolerated, bioequivalent to the reference drug, and warrants further testing in a phase III clinical trial.