This study is a randomized, double-blinded, two-treatment, two-period, two-sequence crossover pivotal Biosimilar study. The purpose of this study is to establish pharmacokinetic (PK) and pharmacodynamic (PD) biosimilarity of proposed biosimilar I004 and the US-approved NovoLog.
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Healthy male and female subjects ≥ 18 to ≤ 65 years of age.
Body mass index (BMI) ≥ 18.5 to ≤ 29.9 kg/m2
Weight ≥ 50 kg.
History of diabetes mellitus.
Resting blood pressure (BP) > 140/90 mmHg or < 90/60 mmHg. Subjects BP may be re-checked.
Participation in an investigational drug/device study within 30 days or 5 half-lives within the last dose of any study drug, whichever is longer.
History of any serious adverse reaction or hypersensitivity to any of the investigational product components.
Crossover
I004
DrugDrug will be administered via subcutaneous injection into the abdominal wall of the peri-umbilical area with a dose of 0.2 units/kg based on the body weight measured at Day -1 of Treatment Period 1 under fasting condition.
NovoLog
DrugDrug will be administered via subcutaneous injection into the abdominal wall of the peri-umbilical area with a dose of 0.2 units/kg based on the body weight measured at Day -1 of Treatment Period 1 under fasting condition.
Maximum Serum Insulin Aspart Concentration, CIAmax
Pharmacokinetic (PK) blood samples will be collected from 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 12 Hours Post-dose, AUCIA(0-12h)
Pharmacokinetic (PK) blood samples will be collected from 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart. AUCIA(0-12h) will be calculated from the concentration curves. Only AUC from 0 to 12 hours (AUCIA(0-12h)) is reported.
Maximum Glucose Infusion Rate, Gmax
Participants will undergo a euglycemic clamp, where blood glucose concentration will be held at a constant target level by adjusting exogenous glucose infusion rate (GIR) following drug administration. GIR will be recorded for the duration of the euglycemic clamp and used to evaluate the Pharmacodynamic (PD) response.
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 12 Hours Post-dose, AUCG(0-12h)
Participants will undergo a euglycemic clamp, where blood glucose concentration will be held at a constant target level by adjusting exogenous glucose infusion rate (GIR) following drug administration. GIR will be recorded for the duration of the euglycemic clamp and used to evaluate the Pharmacodynamic (PD) response. AUCG(0-12h) will be calculated from the glucose infusion rate curves. Because GIR is recorded in mg/kg/min, the area under the GIR-time curve has units mg/kg.
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to Infinity, AUCIA(0-∞)
Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart. AUCIA(0-∞) will be calculated from the concentration curves. AUCIA(0-∞) is derived using standard extrapolation beyond the last measurable concentration.
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 2 Hours Post-dose, AUCIA(0-2h)
Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart. AUCIA(0-2h) will be calculated from the concentration curves. Only AUC from 0 to 2 hours (AUCIA(0-2h)) is reported.
Time of Maximum Insulin Aspart Serum Concentration, tIAmax
Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart.
Apparent Clearance of Insulin Aspart (CL/F)
Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart.
Systolic Blood Pressure (SBP)
Participant vital signs were measured in a supine position, after a 5-minute resting period, before drug administration (baseline) and at specified time points after dosing.
Diastolic Blood Pressure (DBP)
Participant vital signs were measured in a supine position, after a 5-minute resting period, before drug administration (baseline) and at specified time points after dosing.
Heart Rate (HR)
Participant vital signs were measured in a supine position, after a 5-minute resting period, before drug administration (baseline) and at specified time points after dosing.
QT Interval
A standard 12-lead electrocardiogram (ECG) was recorded in a supine position, after a 5-minute resting period, before drug administration (baseline) and at specified time points after dosing.
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