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

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

Single-centre, randomised, double-blind, single dose, two-treatment, two-period, two sequence, crossover,12-hour euglycaemic glucose clamp trial in healthy subjects

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany
    • Profil Mainz GmbH

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 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.

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 R; 0.3 IU/kg Dose per administration, subcutaneous Route of administration	Biological: Biocon Insulin R; Biocon Insulin R is a short-acting human insulin, produced by recombinant deoxyribonucleic acid (rDNA) technology utilizing Pichia pastoris (yeast).
Active Comparator: Humulin® R (regular insulin human); 0.3 IU/kg Dose per administration, subcutaneous Route of administration	Biological: Humulin®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.

What is the study measuring?

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

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 to Follow-up period (Total duration: 35 days approximate)

Collaborators and Investigators

• Sponsor: Biocon Limited
• Collaborators: Profil Institut für Stoffwechselforschung GmbH
• Investigators: Principal Investigator: Dr. Leona P Mörschel, Profil Mainz GmbH

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2019
• Primary Completion (Actual): September 15, 2019
• Study Completion (Actual): September 20, 2019

Study Registration Dates

• First Submitted: June 29, 2019
• First Submitted That Met QC Criteria: July 13, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 27, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Recombinant Human Insulin R (rhi R)
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: EQR

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