Comparison of Pharmacokinetic (PK) and Pharmacodynamic(PD) of Biocon Insulin 70/30 and Humulin® 70/30

Study Overview
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Brief Summary
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Two-centre, randomised, double-blind, single dose, two-treatment, two-period, two sequence, crossover, 24-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 70/30 with Humulin® 70/30 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 dosing. The planned trial duration for each subject is about 12 to 36 days. Eligible subjects will undergo two 24-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 70/30 and Humulin® 70/30

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Biological: Humulin ®70/30
* Biological: Biocon Insulin 70/30


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or post-menopausal female subjects. 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 randomization 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 70/30<br>0.4 IU/kg Dose per administration, Subcutaneous Route of administration | Biological: Biocon Insulin 70/30<br>* Biocon Insulin 70/30 is a premixed suspension of human insulin of recombinant deoxyribonucleic acid (rDNA)origin, which contains 30% short-acting human soluble insulin and 70% intermediate-acting isophane insulin. Biocon insulin is produced by recombinant deoxyribonucleic acid (rDNA) technology utilizing a non-pathogenic laboratory strain of Escherichia coli.<br>|
| Active Comparator: Humulin® 70/30<br>0.4 IU/kg Dose per administration, Subcutaneous Route of administration | Biological: Humulin ®70/30<br>* Humulin® 70/30 is a premixed suspension of human insulin of recombinant deoxyribonucleic acid (rDNA)origin, which contains 30% short-acting human soluble insulin and 70% intermediate-acting isophane insulin. Human insulin is produced by recombinant deoxyribonucleic acid (rDNA), technology utilizing a non-pathogenic laboratory strain of Escherichia coli.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic endpoints: area under the insulin concentration curve (AUCins) 0-24h | area under the insulin concentration curve | 0-24hour | 
| Pharmacokinetic endpoints: insulin concentration (Cins).max | maximum observed insulin concentration. | 0-24hour | 
| Pharmacodynamic Endpoint: Area under curve (AUC)Glucose infusion rate (GIR).0-24h | area under the glucose infusion rate curve | 0-24hour | 
| Pharmacodynamic Endpoint: maximum glucose infusion rate (GIRmax) | maximum glucose infusion rate | 0-24hour | 

Secondary Outcome Measures

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