Healthy Volunteer
Conditions
Keywords
Recombinant Human Insulin R (rhi R)
Brief summary
Single-centre, randomised, double-blind, single dose, two-treatment, two-period, two sequence, crossover,12-hour euglycaemic glucose clamp trial in healthy subjects
Detailed description
The present study is designed to demonstrate pharmacokinetic and pharmacodynamic equivalence of Biocon Insulin R with Humulin® R in healthy subjects. The treatment consists of one single dose of the test or reference product, administered during each of the two study periods, separated by 5-7 days between each dosing. The planned trial duration for each subject is about 12 to 36 days. Eligible subjects will undergo two 12-hour euglycaemic clamp examinations, one after administration of the test product and one after administration of the reference product in random order.
Interventions
BIOLOGICALBiocon Insulin R
Biocon Insulin R is a short-acting human insulin, produced by recombinant deoxyribonucleic acid (rDNA) technology utilizing Pichia pastoris (yeast).
BIOLOGICALHumulin®R
Humulin® R is a polypeptide hormone structurally identical to human insulin synthesised through recombinant deoxyribonucleic acid (rDNA) technology in a non-pathogenic laboratory strain of Escherichia coli bacteria.
Sponsors
Profil Institut für Stoffwechselforschung GmbH
Biocon Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or post-menopausal female subject. 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/m\^2, both inclusive. * Fasting plasma glucose concentration \<= 100 mg/dL. * Considered generally healthy upon completion of medical history and screening safety assessments, as judged by the Investigator
Exclusion criteria
* Known or suspected hypersensitivity to Investigational Medicinal products (IMP(s)) 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. * Any history or presence of clinically relevant comorbidity, as judged by the investigator. * Systolic blood pressure \< 95 mmHg or \>140 mmHg and/or diastolic blood pressure \< 50 mm Hg or \> 90 mmHg after resting for at least 5 minutes in 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 |
|---|---|---|
| PD endpoints:maximum glucose infusion rate(GIRmax) | 0-12 hours | maximum glucose infusion rate |
| PK endpoints: Maximum observed insulin concentration(Cins.max) | 0-12 hours | Maximum observed insulin concentration |
| PK endpoints:Area under the insulin concentration curve(AUCins).0-12h | 0-12 hours | Area under the insulin concentration curve from 0 to 12 hours. |
| PD endpoints: Area under the glucose infusion rate curve(AUCGIR).0-12h | 0-12 hours | Area under the glucose infusion rate curve |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK endpoint- Area under the insulin concentration curve(AUCins).0-6h | 0 to 6 hours | area under the insulin concentration curve |
| PK endpoint- Area under the insulin concentration curve(AUCins).6-12h | 6 to 12 hours | area under the insulin concentration curve |
| PK endpoint- Area under the insulin concentration curve(AUCins).0-infinity | 0 hours to 24 hours | area under the insulin concentration-time curve |
| PK endpoint- time to maximum concentration( tmax) | 0-12 hours | time to maximum observed insulin concentration. |
| PK endpoint- terminal elimination half-life (t½) | 0-12 hours | terminal elimination half-life calculated as t½=ln2/λz. |
| PK endpoint- terminal elimination rate constant (λz) | 0-12 hours | terminal elimination rate constant of insulin. |
| PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-6h | 0 to 6 hours | area under the glucose infusion rate curve |
| PD endpoint: area under the glucose infusion rate curve(AUCGIR).6-12h | 6 to 12 hours | area under the glucose infusion rate curve |
| PD endpoint: time to maximum glucose infusion rate (tGIR.max) | 0-12 hours | time to maximum glucose infusion rate |
| PD endpoint: time to half-maximum glucose infusion rate before GIRmax (tGIR,50%-early | 0-12 hours | time to half-maximum glucose infusion rate before GIRmax |
| PD endpoint:time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late) | 0-12 hours | time to half-maximum glucose infusion rate after Maximum glucose infusion rate(GIRmax) |
| PD endpoint: Onset of action | 0-12 hours | ime from trial product administration until blood glucose concentration has decreased at least 5 mg/dL from baseline, where baseline is defined as the mean of blood glucose levels from -6, -4, and -2 minutes before trial product administration as measured by ClampArt®((name of Clamp Devise) |
| PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-2h | 0 to 2 hours | area under the glucose infusion rate curve |
| PK endpoint- time(t)50%-ins(early) | 0-12 hours | time to half-maximum before Cins.max. |
| PK endpoint- time(t)50%-ins(late) | 0-12 hours | time to half-maximum after Cins.max. |
| PK endpoint- Area under the insulin concentration curve(AUCins).0-2h | 0 to 2 hours | Area under the insulin concentration curve |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety endpoints: Number of subjects with Adverse Events, clinically significant changes in Physical examination, Vital signs. Local tolerability/ Injection site reactions | First dose to followup period (Total duration: 14 days approximate) | Number of subjects with Adverse Events, clinically significant changes in Physical examination, Vital signs Local tolerability/ Injection site reactions |
| Safety endpoint: Number of subjects with clinically significant changes in Laboratory safety parameters, Electrocardiogram (ECG) | Screening to Follow-up period (Total duration: 35 days approximate) | Number of subjects with clinically significant changes in Laboratory safety parameters. Number of subjects with clinically significant changes in Electrocardiogram (ECG) |
Countries
Germany
Outcome results
None listed