Comparision of Pharmacokinetics(PK) and Pharmacodynamics(PD) of Biocon Insulin R and Humulin® R

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomised, Double-blind, Two-period Crossover, Euglycaemic Glucose Clamp Study in Healthy Volunteers to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity of Biocon Insulin R and Humulin® R

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Biological: Biocon Insulin R
* Biological: Humulin®R


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biocon Insulin R<br>0.3 IU/kg Dose per administration, subcutaneous Route of administration | Biological: Biocon Insulin R<br>* Biocon Insulin R is a short-acting human insulin, produced by recombinant deoxyribonucleic acid (rDNA) technology utilizing Pichia pastoris (yeast).<br>|
| Active Comparator: Humulin® R (regular insulin human)<br>0.3 IU/kg Dose per administration, subcutaneous Route of administration | Biological: Humulin®R<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK endpoints:Area under the insulin concentration curve(AUCins).0-12h | Area under the insulin concentration curve from 0 to 12 hours. | 0-12 hours | 
| PD endpoints: Area under the glucose infusion rate curve(AUCGIR).0-12h | Area under the glucose infusion rate curve | 0-12 hours | 
| PK endpoints: Maximum observed insulin concentration(Cins.max) | Maximum observed insulin concentration | 0-12 hours | 
| PD endpoints:maximum glucose infusion rate(GIRmax) | maximum glucose infusion rate | 0-12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK endpoint- Area under the insulin concentration curve(AUCins).0-2h | Area under the insulin concentration curve | 0 to 2 hours | 
| PK endpoint- Area under the insulin concentration curve(AUCins).0-6h | area under the insulin concentration curve | 0 to 6 hours | 
| PK endpoint- Area under the insulin concentration curve(AUCins).6-12h | area under the insulin concentration curve | 6 to 12 hours | 
| PK endpoint- Area under the insulin concentration curve(AUCins).0-infinity | area under the insulin concentration-time curve | 0 hours to 24 hours | 
| PK endpoint- time to maximum concentration( tmax) | time to maximum observed insulin concentration. | 0-12 hours | 
| PK endpoint- time(t)50%-ins(early) | time to half-maximum before Cins.max. | 0-12 hours | 
| PK endpoint- time(t)50%-ins(late) | time to half-maximum after Cins.max. | 0-12 hours | 
| PK endpoint- terminal elimination half-life (t½) | terminal elimination half-life calculated as t½=ln2/λz. | 0-12 hours | 
| PK endpoint- terminal elimination rate constant (λz) | terminal elimination rate constant of insulin. | 0-12 hours | 
| PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-2h | area under the glucose infusion rate curve | 0 to 2 hours | 
| PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-6h | area under the glucose infusion rate curve | 0 to 6 hours | 
| PD endpoint: area under the glucose infusion rate curve(AUCGIR).6-12h | area under the glucose infusion rate curve | 6 to 12 hours | 
| PD endpoint: time to maximum glucose infusion rate (tGIR.max) | time to maximum glucose infusion rate | 0-12 hours | 
| PD endpoint: time to half-maximum glucose infusion rate before GIRmax (tGIR,50%-early | time to half-maximum glucose infusion rate before GIRmax | 0-12 hours | 
| PD endpoint:time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late) | time to half-maximum glucose infusion rate after Maximum glucose infusion rate(GIRmax) | 0-12 hours | 
| PD endpoint: Onset of action | 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) | 0-12 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recombinant Human Insulin R (rhi R)