Pharmacokinetic and pharmacodynamic equivalence of Biocon's biosimilar insulin N with US‐licensed Humulin® N formulation in healthy subjects: Results from the RHINE‐2 (Recombinant Human INsulin Equivalence‐2) study

To establish the pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of proposed biosimilar Insulin N (Biocon's Insulin-N; Biocon Biologics Ltd., Bangalore, India) and US-licensed Humulin® N (Humulin-N; Eli Lilly and Company, Indianapolis, IN, USA) in healthy subjects.This was a phase-1, single-centre, double-blind, randomized, three-period, six-sequence, partially replicated, crossover, 24-h euglycaemic clamp study. Overall, 90 healthy subjects were randomized, of whom 85 completed the study. The subjects received either two single doses of Biocon's Insulin-N and a single dose of Humulin-N or two single doses of Humulin-N and a single dose of Biocon's Insulin-N subcutaneously at a dose of 0.4 IU/kg. The primary PK endpoints were the area under the insulin concentration-time curve from 0 to 24 h (AUCins.0-24h ) and the maximum insulin concentration (Cins.max ). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 h (AUCGIR.0-24h ) and the maximum GIR (GIRmax ).Biocon's Insulin-N was found to be equivalent to Humulin-N for the primary PK (geometric 90% confidence interval for the least squares mean ratio: AUCins.0-24h , 100.98%-115.66% and Cins.max , 95.91%-110.16%) and PD endpoints (intra-subject variability ≥0.294; 95% upper confidence interval [(μT - μR)2 - θσ2 WR] <0; point estimates of geometric least squares mean ratio: AUCGIR.0-24h , 104.61% and GIRmax , 100.81%). The safety profile of Biocon's Insulin-N was similar to that of Humulin-N, and no serious adverse events were reported.PK and PD equivalence was shown between Biocon's Insulin-N and Humulin-N in healthy subjects, and both treatments were well tolerated and considered safe.