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

Healthy Volunteer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04022317
• Other study ID #: EQR
• Status: Completed
• Phase: Phase 1
• Start date: June 18, 2019
• Est. completion date: September 20, 2019

Study information

• Verified date: July 2021
• Source: Biocon Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 20, 2019
• Est. primary completion date: September 15, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Biological:
• Biocon Insulin R
Biocon Insulin R is a short-acting human insulin, produced by recombinant deoxyribonucleic acid (rDNA) technology utilizing Pichia pastoris (yeast).
• 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.

Locations

Country	Name	City	State
Germany	Profil Mainz GmbH	Mainz

Sponsors (2)

Lead Sponsor	Collaborator
Biocon Limited	Profil Institut für Stoffwechselforschung GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Primary	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
Primary	PD endpoints: Area under the glucose infusion rate curve(AUCGIR).0-12h	Area under the glucose infusion rate curve	0-12 hours
Primary	PK endpoints: Maximum observed insulin concentration(Cins.max)	Maximum observed insulin concentration	0-12 hours
Primary	PD endpoints:maximum glucose infusion rate(GIRmax)	maximum glucose infusion rate	0-12 hours
Secondary	PK endpoint- Area under the insulin concentration curve(AUCins).0-2h	Area under the insulin concentration curve	0 to 2 hours
Secondary	PK endpoint- Area under the insulin concentration curve(AUCins).0-6h	area under the insulin concentration curve	0 to 6 hours
Secondary	PK endpoint- Area under the insulin concentration curve(AUCins).6-12h	area under the insulin concentration curve	6 to 12 hours
Secondary	PK endpoint- Area under the insulin concentration curve(AUCins).0-infinity	area under the insulin concentration-time curve	0 hours to 24 hours
Secondary	PK endpoint- time to maximum concentration( tmax)	time to maximum observed insulin concentration.	0-12 hours
Secondary	PK endpoint- time(t)50%-ins(early)	time to half-maximum before Cins.max.	0-12 hours
Secondary	PK endpoint- time(t)50%-ins(late)	time to half-maximum after Cins.max.	0-12 hours
Secondary	PK endpoint- terminal elimination half-life (t½)	terminal elimination half-life calculated as t½=ln2/?z.	0-12 hours
Secondary	PK endpoint- terminal elimination rate constant (?z)	terminal elimination rate constant of insulin.	0-12 hours
Secondary	PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-2h	area under the glucose infusion rate curve	0 to 2 hours
Secondary	PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-6h	area under the glucose infusion rate curve	0 to 6 hours
Secondary	PD endpoint: area under the glucose infusion rate curve(AUCGIR).6-12h	area under the glucose infusion rate curve	6 to 12 hours
Secondary	PD endpoint: time to maximum glucose infusion rate (tGIR.max)	time to maximum glucose infusion rate	0-12 hours
Secondary	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
Secondary	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
Secondary	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