Aim To establish equivalence in the pharmacokinetic (PK) and pharmacodynamic (PD) endpoints between proposed biosimilar Insulin‐R (Biocon's Insulin‐R) and Humulin® R using the euglycaemic clamp technique in healthy subjects. Materials and Methods In this phase‐1 automated euglycaemic glucose clamp study, 42 healthy subjects were randomized (1:1) to receive a single dose of 0.3 IU/kg of Biocon's Insulin‐R and Humulin‐R. Plasma insulin concentrations and glucose infusion rates (GIRs) were assessed over 12 hours. Primary PK endpoints were area under the insulin concentration‐time curve from 0 to 12 hours (AUCins.0‐12h) and maximum insulin concentration (Cins.max). Primary PD endpoints were area under the GIR time curve from 0 to 12 hours (AUCGIR.0‐12h) and maximum GIR (GIRmax). Results Equivalence was demonstrated between Biocon's Insulin‐R and Humulin‐R for the primary PK and PD endpoints. The 90% confidence intervals were within 80.00% to 125.00% limits. The PK and PD profiles were comparable. There were no significant differences in the safety profiles of the two treatments, and no serious adverse events were reported. Conclusion PK and PD equivalence was demonstrated between Biocon's Insulin‐R and Humulin‐R in healthy subjects. Treatment with Biocon’s Insulin‐R and Humulin‐R was well tolerated.

Aim 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. Materials and Methods 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). Results 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 − θσ2WR] <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. Conclusion 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.

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Aim To establish the pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of proposed biosimilar insulin 70/30 (Biocon's Insulin‐70/30) and HUMULIN® 70/30 (HUMULIN‐70/30; Eli Lilly and Company, IN). Materials and Methods In this phase 1, automated euglycaemic glucose clamp study, 78 healthy subjects were randomized (1:1) to receive a single dose of 0.4 IU/kg of Biocon's Insulin‐70/30 and HUMULIN‐70/30. Plasma insulin concentrations and glucose infusion rates (GIRs) were assessed over 24 hours. Primary PK endpoints were area under the insulin concentration‐time curve from 0 to 24 hours ‐ AUCins.0−24h ‐ and maximum insulin concentration ‐ Cins.max. Primary PD endpoints were area under the GIR time curve from 0 to 24 hours ‐ AUCGIR.0−24h ‐ and maximum GIR ‐ GIRmax. Results Equivalence was shown between Biocon's Insulin‐70/30 and HUMULIN‐70/30 for the primary PK/PD endpoints. The 90% confidence intervals of the treatment ratios were entirely within the acceptance range of 80.00%‐125.00%. The secondary PK/PD profiles were also comparable. There were no clinically relevant differences in the safety profiles of the two treatments and no serious adverse events were reported. Conclusion PK/PD equivalence was demonstrated between Biocon's Insulin‐70/30 and HUMULIN‐70/30 in healthy subjects. Treatment with Biocon's Insulin‐70/30 and HUMULIN‐70/30 was well tolerated.