| Outcome Measures: |
Primary: Area under the concentration-time curve from 0 hours to 24 hours (AUC0-24h) of M1, The Pharmacokinetics (PK) parameters of HEC-Glargine to the US-approved Lantus® insulin glargine injection (US-Lantus®) solution for SC injection to demonstrate PK similarity for insulin glargine and/or metabolite 21A-Gly-human insulin (M1) will be assessed., Day 1 and Day 2|Maximum observed plasma exogenous insulin glargine concentration (Cmax) of M1, The PK parameters of HEC-Glargine to the US-approved Lantus® insulin glargine injection (US-Lantus®) solution for SC injection to demonstrate PK similarity for insulin glargine and/or metabolite 21A-Gly-human insulin (M1) will be assessed., Day 1 and Day 2|Area under the Glucose infusion rate (GIR) -time curve (calculated as the exact area under the stepwise constant function) from 0 hours to 24 hours (GIRAUC0-24h), The pharmacodynamics (PD) of HEC-Glargine to US-Lantus®, by means of GIR profiles after single SC dose will be assessed., Day 1 and Day 2|Maximum GIR (GIRmax), The PD of HEC-Glargine to US-Lantus®, by means of GIR profiles after single SC dose will be assessed., Day 1 and Day 2 | Secondary: Area under the concentration-time curve from 0 hours to the last quantifiable concentration-time (AUC0-t), The PK parameters of HEC-Glargine, US-Lantus®, and M1 will be assessed. Also, AUC0-t will be evaluating the inter-subject and intra-subject variability of PK of HEC-Glargine in comparison to US-Lantus®, assessed by intra-subject coefficients of variation for primary PK parameters., Day 1 and Day 2|Area under the concentration-time curve from 0 hours to 6 hours (AUC0-6h), The PK parameters of HEC-Glargine, US-Lantus®, and M1 will be assessed., Day 1 and Day 2|Area under the concentration-time curve from 6 hours to 12 hours (AUC6-12h), The PK parameters of HEC-Glargine, US-Lantus®, and M1 will be assessed., Day 1 and Day 2|Area under the concentration-time curve from 0 hours to 12 hours (AUC0-12h), The PK parameters of HEC-Glargine, US-Lantus®, and M1 will be assessed., Day 1 and Day 2|Area under the concentration-time curve from 12 hours to 18 hours (AUC12-18h), The PK parameters of HEC-Glargine, US-Lantus®, and M1 will be assessed., Day 1 and Day 2|Area under the concentration-time curve from 18 hours to 24 hours (AUC18-24h), The PK parameters of HEC-Glargine, US-Lantus®, and M1 will be assessed., Day 1 and Day 2|Area under the concentration-time curve from 12 hours to 24 hours (AUC12-24h), The PK parameters of HEC-Glargine, US-Lantus®, and M1 will be assessed., Day 1 and Day 2|Time to maximum plasma exogenous insulin glargine concentration (Tmax), The PK parameters of HEC-Glargine, US-Lantus®, and M1 will be assessed., Day 1 and Day 2|Area under the concentration-time curve from 0 hours to the last quantifiable concentration-time extrapolated to infinity (AUC0-∞), The PK parameters of HEC-Glargine, US-Lantus®, and M1 will be assessed., Day 1 and Day 2|Area under the GIR-time curve for the time of a dosing interval (GIRAU0-t), The PD parameters of HEC-Glargine, US-Lantus® will be assessed. Also, GIRAU0-t will be evaluating the inter-subject and intra-subject variability of PD of HEC-Glargine in comparison to US-Lantus®, assessed by intra-subject coefficients of variation for primary PD parameters., Day 1 and Day 2|Area under the GIR-time curve from 0 hours to end of clamp (GIRAUC0-end of clamp), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Area under the GIR-time curve from 0 hours to the last quantifiable concentration-time with extrapolation to infinity (GIRAUC0-∞), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Area under the GIR-time curve from 0 hours to 6 hours (GIRAUC0-6h), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Area under the GIR-time curve from 6 hours to 12 hours (GIRAUC6-12h), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Area under the GIR-time curve from 0 hours to 12 hours (GIRAUC0-12h), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Area under the GIR-time curve from 12 hours to18 hours (GIRAUC12-18h), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Area under the GIR-time curve from 18 hours to 24 hours (GIRAUC18-24h), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Area under the GIR-time curve from 12 hours to 24 hours (GIRAUC12-24h), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Time to maximum glucose infusion rate (TGIRmax), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Total amount of glucose infused during clamp procedure (Gtot), The PD parameters of HEC-Glargine, US-Lantus® will be assessed., Day 1 and Day 2|Time to onset of action (TOA), The TOA will be assessed for HEC-Glargine, US-Lantus® as PD parameters., Day 1 and Day 2|Maximum observed plasma exogenous insulin glargine concentration (Cmax), The Cmax will be evaluating the inter-subject and intra-subject variability of PK of HEC-Glargine in comparison to US-Lantus®, assessed by intra-subject coefficients of variation for primary PK parameters., Day 1 and Day 2|Maximum GIR (GIRmax), The GIRmax will be evaluating the inter-subject and intra-subject variability of PD of HEC-Glargine in comparison to US-Lantus®, assessed by intra-subject coefficients of variation for primary PD parameters., Day 1 and Day 2|Number of subjects with adverse events (AEs), To assess safety and tolerability of the HEC-Glargine compared to US-Lantus® after single SC dose To assess safety and tolerability of the HEC-Glargine compared to US-Lantus® after single SC dose, Day -1 to within 7 Days of completion of the last period or early withdrawal (approximately 31 days)
|
