Abstract
Background and Aims
A biosimilar is a biological medicine highly similar to already approved biological reference medicine. The program of clinical trials of insulin biosimilars includes pharmacology studies: pharmacokinetics (PK) – concentration-time and pharmacodynamics (PD) – glucose infusion rate (GIR)-time. The aim of this study was to test if GP40061 – a biosimilar to reference insulin glargine (RIG) – has similar PK and PD profiles in a hyperinsulinemic euglycaemic clamp (HEC) setting in patients with type 1 diabetes mellitus (T1DM).
Methods
A double-blind, randomized, crossover study enrolled 42 adult patients with T1DM. The study was conducted in accordance with international guidelines for HEC studies. Each patient received a single dose of insulin (0.6 U/kg) subcutaneously. Regular blood sampling was performed. The amount of insulin glargine in the samples was determined by enzyme-linked immunosorbent assay. The primary endpoints were AUCins.0-24 (PK) and AUCGIR.0-24 (PD).We calculated the 90% (PK) and 95% (PD) confidence intervals (CI) of the GP40061/RIG geometric mean ratio for primary endpoints. Similarity of PK and PD is proved if CIs fall within the specified limits of 80%─125%. Secondary endpoints were AUCins.0-12 and AUCins.12-24 (PK), AUCGIR.0-12 and AUCGIR.12-24 (PD). Safety was also assessed.
Results
CIs were 81.02%─120.62% for AUCins.0-24 and 85.43%─115.64% for AUCGIR0-24. Ratio of AUCins.0-12 was 95.39%, AUCins.12-24 – 106.45%, AUCGIR.0-12 – 93.39% and AUCGIR.12-24 – 92.55%. Adverse events were registered in 11 patients in GP40061 and 9 patients on RIG (p=1.000).
Conclusions
GP40061 demonstrated similar PK and PD profiles to RIG. The study results proved biosimilarity of GP40061 to reference insulin glargine.
