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

Phase 1

Completed

• Conditions: Healthy Volunteer
• Interventions: Biological: Humulin ®70/30; Biological: Biocon Insulin 70/30

• Registration Number: NCT04022291
• Lead Sponsor: Biocon Limited

Brief Summary

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

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.

Study Timeline

• Study Start: 2019-06-15
• Study First Submitted: 2019-07-04
• Study First Submitted QC: 2019-07-13
• Study First Posted: 2019-07-17
• Status Verified: 2020-01
• Primary Completion: 2020-01-20
• Study Completion: 2020-01-27
• Last Update Submitted: 2020-01-29
• Last Update Posted: 2020-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Humulin® 70/30	Humulin ®70/30	0.4 IU/kg Dose per administration, Subcutaneous Route of administration
Biocon Insulin 70/30	Biocon Insulin 70/30	0.4 IU/kg Dose per administration, Subcutaneous Route of administration

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Profil Institut für Stoffwechselforschung GmbH Hellersbergstr. 9 D-41460 Neuss; 🇩🇪 Neuss, Germany

Profil Mainz GmbH & Co. KG Malakoff-Passage,Rheinstraße 4C D-55116; 🇩🇪 Mainz, Germany