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

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 70/30 and Humulin® 70/30

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04022291
• Other study ID #: EQ7030
• Status: Completed
• Phase: Phase 1
• Start date: June 15, 2019
• Est. completion date: January 27, 2020

Study information

• Verified date: January 2020
• Source: Biocon Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: January 27, 2020
• Est. primary completion date: January 20, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

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.
• 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.

Locations

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

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 and Follow-up period (Total duration: 35 days approximate)
Primary	Pharmacokinetic endpoints: area under the insulin concentration curve (AUCins) 0-24h	area under the insulin concentration curve	0-24hour
Primary	Pharmacokinetic endpoints: insulin concentration (Cins).max	maximum observed insulin concentration.	0-24hour
Primary	Pharmacodynamic Endpoint: Area under curve (AUC)Glucose infusion rate (GIR).0-24h	area under the glucose infusion rate curve	0-24hour
Primary	Pharmacodynamic Endpoint: maximum glucose infusion rate (GIRmax)	maximum glucose infusion rate	0-24hour
Secondary	Pharmacokinetic endpoint: area under the insulin concentration curve(AUCins) 0-2h	area under the insulin concentration curve	0-2hour
Secondary	Pharmacokinetic endpoint: area under the insulin concentration curve(AUCins) 0-6h	area under the insulin concentration curve	0-6hour
Secondary	Pharmacokinetic endpoint: area under the insulin concentration curve(AUCins) 0-12h	area under the insulin concentration curve	0-12hour
Secondary	Pharmacokinetic endpoint: area under the insulin concentration curve(AUCins)12-24h	area under the insulin concentration curve	12-24hour
Secondary	Pharmacokinetic endpoint: area under the insulin concentration curve(AUCins).0-infinity	area under the insulin concentration curve	0 to 24 hours
Secondary	Pharmacokinetic endpoint: time to maximum observed insulin concentration (tmax)	time to maximum observed insulin concentration	0-24hour
Secondary	Pharmacokinetic endpoint: time(t)50%-ins(early)	time to half-maximum before Cins.max	0-24hour
Secondary	Pharmacokinetic endpoint: time(t)50%-ins(late)	time to half-maximum after Cins.max	0-24hour
Secondary	Pharmacokinetic endpoint: terminal elimination half-life (t½)	terminal elimination half-life calculated as t½=ln2/?z	0-24hour
Secondary	Pharmacokinetic endpoint:terminal elimination rate constant(?z)	terminal elimination rate constant of insulin	0-24hour
Secondary	Pharmacodynamic endpoints: area under the glucose infusion rate curve (AUCGIR) 0-2h	area under the glucose infusion rate curve	0-2hour
Secondary	Pharmacodynamic endpoints: area under the glucose infusion rate curve (AUCGIR)0-6h	area under the glucose infusion rate curve	0-6hour
Secondary	Pharmacodynamic endpoints: area under the glucose infusion rate curve(AUCGIR)0-12h	area under the glucose infusion rate curve	0-12hour
Secondary	Pharmacodynamic endpoints: area under the glucose infusion rate curve (AUCGIR)12-24h	area under the glucose infusion rate curve	12-24hour
Secondary	Pharmacodynamic endpoints: time to maximum glucose infusion rate (tGIR.max)	time to maximum glucose infusion rate	0-24hour
Secondary	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
Secondary	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
Secondary	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