Pharmacokinetics and Safety of iGlarLixi in Healthy Chinese Participants: Results of a Phase 1 Randomized Study

Panpan Xie; Xuemei He; Xin Gao; Mengmeng Shuai; Wolfgang Schmider; Alex Jiang; Na Yang; Aixin Shi

doi:10.1007/s13300-023-01434-0

Pharmacokinetics and Safety of iGlarLixi in Healthy Chinese Participants: Results of a Phase 1 Randomized Study

Diabetes Ther. 2023 Aug;14(8):1387-1397. doi: 10.1007/s13300-023-01434-0. Epub 2023 Jun 17.

Authors

Panpan Xie¹, Xuemei He¹, Xin Gao¹, Mengmeng Shuai², Wolfgang Schmider³, Alex Jiang⁴, Na Yang², Aixin Shi⁵

Affiliations

¹ Clinical Trial Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
² Sanofi, Beijing, People's Republic of China.
³ Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.
⁴ Sanofi, Shanghai, People's Republic of China.
⁵ Clinical Trial Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. aixins0302@126.com.

Abstract

Introduction: The Chinese Diabetes Society recommends basal insulin and glucagon-like peptide-1 receptor agonists as an add-on therapy to first-line oral antihyperglycemic drugs for people with type 2 diabetes (T2D). Fixed-ratio combination of insulin glargine 100 U/ml (iGlar) and lixisenatide (iGlarLixi) is known to improve glycemic control in adults with T2D. However, the pharmacokinetics of iGlarLixi has not been evaluated in Chinese participants. The present study evaluated pharmacokinetics and safety of two iGlarLixi (10 U/10 μg and 30 U/15 μg) doses following single subcutaneous administration in healthy Chinese participants.

Methods: This was a Phase 1, single-center, open-label, parallel-group, randomized study in healthy Chinese adults who were randomized to receive a single dose of iGlarLixi with either 1:1 (10 U/10 μg) or 2:1 (30 U/15 μg) ratio of iGlar and lixisenatide. Primary objectives include assessment of pharmacokinetics of iGlar in iGlarLixi 30 U/15 μg group and the pharmacokinetics of lixisenatide in both the groups (iGlarLixi 10 U/10 μg and iGlarLixi 30 U/15 μg). Safety and tolerability were also assessed.

Results: In iGlarLixi 30 U/15 μg group, iGlar concentrations were low and quantifiable in three of ten participants, while its main metabolite (M1) was quantifiable in all participants, reflecting rapid conversion of iGlar to M1. Median INS-t_max was 14.00 h for iGlar and 13.00 h post-dose for M1. Absorption of lixisenatide was similar in both dose groups with median t_max of 3.25 and 2.00 h post-dose in both groups. The exposure increase was dose proportionate with a 1.5-fold increase in the lixisenatide dose. Adverse events observed were consistent with those previously reported with iGlar or lixisenatide.

Conclusion: iGlarLixi administration resulted in early absorption of both iGlar and lixisenatide with a good tolerability profile in healthy Chinese participants. These results are consistent with the previously published data from other geographic regions.

Trial registration: U1111-1194-9411.

Keywords: Half-life; Insulin glargine; Lixisenatide; Pharmacokinetic; iGlarLixi.