Healthy Volunteers
Conditions
Keywords
Recombinant Human INsulin Equivalence-4, RHINE-4, Pharmacokinetic, Pharmacodynamic, Biocon's Insulin R U-500, Humulin® R U-500
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.
Interventions
BIOLOGICALBiocon's Human Insulin R U-500
Biocon's Human Insulin R U-500 (Insulin Human Injection 500 units/mL), 3 mL cartridges (containing 1,500 units of insulin).
BIOLOGICALHumulin® R U-500 (US Reference Product)
Humulin® R U-500 (US Reference Product), 3 mL single-patient-use KwikPen® (containing 1,500 units of insulin)
Sponsors
Profil Institut für Stoffwechselforschung GmbH
Biocon Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Intervention model description
Partially replicated design, crossover trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Primary pharmacokinetics (PK) endpoint: maximum observed insulin concentration(Cins.max) | NAP (Not Applicable) | Maximum observed insulin concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary pharmacokinetics (PK) endpoint: time(t)50%-Insulin (INS)(early) | 0 to 24 hours | Time to half-maximum before Cmax |
| 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 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 |
| 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: 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 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).12-24h | 12 to 24 hours | Area under the insulin concentration-time curve |
| 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: 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).0-24h | 0 to 24 hours | Area under the insulin concentration-time curve |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety endpoint: Number of subjects with clinically significant changes in ECG | Signing of Informed consent form (ICF) to follow-up period (Total duration:44 days approximate) | — |
| Safety endpoint: Number of subjects with clinically significant changes in Laboratory safety parameters | Signing of Informed consent form (ICF) to follow-up period (Total duration:44 days approximate) | — |
| Safety endpoint: Number of subjects with Adverse Events (AEs) | Signing of Informed consent form (ICF) to follow-up period (Total duration: 44 days approximate) | — |
| Safety endpoint: Local tolerability assessment / Injection site reactions | Signing of Informed consent form (ICF) to follow-up period (Total duration:44 days approximate) | Number of subjects with Injection Site Reactions |
| Safety endpoint: Number of subjects with Clinically significant changes in Vital signs | Signing of Informed consent form (ICF) to follow-up period (Total duration: 44 days approximate) | — |
| Safety endpoint: Number of subjects with Clinically significant changes in Physical examination | Signing of Informed consent form (ICF) to follow-up period (Total duration: 44 days approximate) | — |
Countries
Germany
Outcome results
None listed