Comparison of the Pharmacokinetic and Pharmacodynamic Properties of Biocon's Insulin R U-500 With Humulin® R U-500 (US Reference Product) in Healthy Subjects
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Biological: Biocon's Human Insulin R U-500Biological: Humulin® R U-500 (US Reference Product)
- Registration Number
- NCT05413863
- Lead Sponsor
- Biocon Limited
- Brief Summary
Single-centre, randomised, double-blind, three-period, six-sequence, partially replicated design, crossover trial in healthy subjects
- Detailed Description
The present study is designed to demonstrate pharmacokinetic and pharmacodynamic equivalence of Biocon's Human Insulin R U-500 with Humulin® R U-500 in healthy subjects.
The treatment consists of one single dose of the test or reference product, administered during each of the three study periods, separated by 5-7 days between each dosing. The planned trial duration for each subject is about 18 to 44 days. Eligible subjects will undergo three euglycaemic clamp examinations (each of 24 hours duration).
Depending on the sequence in which a particular subject is randomized, each subject will either undergo two clamps with administration of test product plus one clamp with administration of reference product, or, two clamps with administration of reference product plus one clamp with administration of test product, in random order.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 78
Inclusion Criteria
- Healthy male or post-menopausal female subjects. The post-menopausal state is defined as no menses for 12 months without an alternative medical cause and confirmed by a follicle stimulating hormone (FSH) level in the post-menopausal range (≥ 25.8 IU/L).
- Age between 18 and 55 years, both inclusive.
- Body Mass Index (BMI) between 18.5 and 29.0 kg/m2, both inclusive.
- Fasting plasma glucose concentration ≤ 100 mg/dL.
- Considered generally healthy upon completing the medical history and screening safety assessments, as judged by the Investigator.
Exclusion Criteria
- Known or suspected hypersensitivity to investigational medicinal products (IMPs) or related products.
- Receipt of any medicinal product in clinical development within 30 days or five times its half-life (whichever is longer) before randomisation in this trial.
- Systolic blood pressure < 90 mmHg or > 139 mmHg and/or diastolic blood pressure < 50 mmHg or > 89 mmHg after resting for at least 5 minutes in the supine position (excluding white-coat hypertension; therefore, a repeat test showing results within range will be acceptable).
- Pulse rate at rest outside the range of 50-90 beats per minute.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sequence: Biocon's Human Insulin R U-500-Humulin® R U-500- Humulin® R U-500 Biocon's Human Insulin R U-500 Period 1:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Biocon's Human Insulin R U-500-Humulin® R U-500- Humulin® R U-500 Humulin® R U-500 (US Reference Product) Period 1:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Humulin® R U-500-Humulin® R U-500-Biocon's Human Insulin R U-500 Biocon's Human Insulin R U-500 Period 1:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD(Becton Dickinson) disposable syringe Period 3:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Biocon's Human Insulin R U-500-Biocon's Human Insulin R U-500- Humulin® R U-500 Biocon's Human Insulin R U-500 Period 1:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Biocon's Human Insulin R U-500-Humulin® R U-500-Biocon's Human Insulin R U-500 Humulin® R U-500 (US Reference Product) Period 1:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Humulin® R U-500-Biocon's Human Insulin R U-500-Biocon's Human Insulin R U-500 Humulin® R U-500 (US Reference Product) Period 1:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Biocon's Human Insulin R U-500-Biocon's Human Insulin R U-500- Humulin® R U-500 Humulin® R U-500 (US Reference Product) Period 1:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Humulin® R U-500 -Biocon's Human Insulin R U-500-Humulin® R U-500 Biocon's Human Insulin R U-500 Period 1:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Humulin® R U-500-Biocon's Human Insulin R U-500-Biocon's Human Insulin R U-500 Biocon's Human Insulin R U-500 Period 1:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Biocon's Human Insulin R U-500-Humulin® R U-500-Biocon's Human Insulin R U-500 Biocon's Human Insulin R U-500 Period 1:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Humulin® R U-500 -Biocon's Human Insulin R U-500-Humulin® R U-500 Humulin® R U-500 (US Reference Product) Period 1:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 3:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Sequence: Humulin® R U-500-Humulin® R U-500-Biocon's Human Insulin R U-500 Humulin® R U-500 (US Reference Product) Period 1:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe Period 2:Humulin® R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD(Becton Dickinson) disposable syringe Period 3:Biocon's Human Insulin R U-500 single subcutaneous dose of 0.3 IU/kg using a U-500 BD (Becton Dickinson) disposable syringe
- Primary Outcome Measures
Name Time Method Primary pharmacokinetics (PK) endpoint: maximum observed insulin concentration(Cins.max) NAP (Not Applicable) Maximum observed insulin concentration
Primary pharmacokinetics (PK) endpoint: area under the insulin concentration curve(AUCins).0-12h 0 to12 hours Area under the insulin concentration curve
Primary pharmacodynamics (PD) endpoint:maximum observed glucose infusion rate (GIRmax) NAP (Not Applicable) Maximum observed glucose infusion rate
Primary pharmacodynamics (PD) endpoint:area under the glucose infusion rate curve (AUCGIR)0-12h 0 to 12 hours Area under the glucose infusion rate curve
- Secondary Outcome Measures
Name Time Method Secondary pharmacodynamics (PD) endpoint: areas under the glucose infusion rate curve(AUCGIR).0-24h 0 to 24 hours Area under the glucose infusion rate curve
Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve(AUCins).0-24h 0 to 24 hours Area under the insulin concentration-time curve
Secondary pharmacokinetics (PK) endpoint: time(t)50%-Insulin (INS)(early) 0 to 24 hours Time to half-maximum before Cmax
Secondary pharmacodynamics (PD) endpoint:time to half-maximum glucose infusion rate before GIRmax (tGIR.50%-early) 0 to 24 hours Time to half-maximum glucose infusion rate before GIRmax
Secondary pharmacodynamics (PD) endpoint: Onset of action, time from trial product administration until plasma glucose concentration has decreased at least 5 mg/dL from baseline, 0 to 24 hours Time from trial product administration until plasma glucose concentration
Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve(AUCins).0-infinity 0 hours to 24 hours Area under the insulin concentration-time curve
Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve (AUCins).12-24h 12 to 24 hours Area under the insulin concentration-time curve
Secondary pharmacodynamics (PD) endpoint: time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late) 0 to 24 hours Time to half-maximum glucose infusion rate after GIRmax
Secondary pharmacokinetics (PK) endpoint:time to maximum observed insulin concentration (tmax.ins) 0 to 24 hours Time to maximum observed insulin concentration
Secondary pharmacokinetics (PK) endpoint:terminal elimination rate constant of insulin (λz) 0 to 24 hours Terminal elimination rate constant of insulin
Secondary pharmacokinetics (PK) endpoint: terminal elimination half-life (t½) 0 to 24 hours Terminal elimination half-life calculated
Secondary pharmacokinetics (PK) endpoint: time(t) 50%-Insulin (INS)(late) 0 to 24 hours Time to half-maximum after Cmax
Secondary pharmacodynamics (PD) endpoint: areas under the glucose infusion rate curve(AUCGIR).12-24h 12 to 24 hours Area under the glucose infusion rate curve
Secondary pharmacodynamics (PD) endpoint: time to maximum glucose infusion rate(tmax.GIR) 0 to 24 hours Time to maximum glucose infusion rate
Trial Locations
- Locations (1)
Profil Institut für Stoffwechselforschung GmbH 9
🇩🇪Neuss, Germany