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

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

Two-centre, randomised, double-blind, single dose, two-treatment, two-period, two sequence, crossover, 24-hour euglycaemic glucose clamp trial in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Biological: Biocon Insulin 70/30; Biological: Humulin ®70/30

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 Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany
    • Profil Mainz GmbH & Co. KG Malakoff-Passage,Rheinstraße 4C D-55116
  • Neuss, Germany
    • Profil Institut für Stoffwechselforschung GmbH Hellersbergstr. 9 D-41460 Neuss

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biocon Insulin 70/30; 0.4 IU/kg Dose per administration, Subcutaneous Route of administration	Biological: Biocon Insulin 70/30; 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.
Active Comparator: Humulin® 70/30; 0.4 IU/kg Dose per administration, Subcutaneous Route of administration	Biological: Humulin ®70/30; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoints: Number of subjects with Adverse Events, clinically significant changes in Physical examination, Vital signs. Local tolerability/ Injection site reactions	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)
Safety endpoint: Number of subjects with clinically significant changes in Laboratory safety parameters, Electrocardiogram (ECG)	Number of subjects with clinically significant changes in Laboratory safety parameters. Number of subjects with clinically significant changes in Electrocardiogram (ECG)	Screening and Follow-up period (Total duration: 35 days approximate)

Collaborators and Investigators

• Sponsor: Biocon Limited
• Collaborators: Profil Institut für Stoffwechselforschung GmbH
• Investigators: Principal Investigator: Oliver Klein, MD, Profil Institut für Stoffwechselforschung GmbH Hellersbergstr. 9 D-41460 Neuss

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2019
• Primary Completion (Actual): January 20, 2020
• Study Completion (Actual): January 27, 2020

Study Registration Dates

• First Submitted: July 4, 2019
• First Submitted That Met QC Criteria: July 13, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2020
• Last Update Submitted That Met QC Criteria: January 29, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: EQ7030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No