Comparision of Pharmacokinetic and Pharmacodynamic of Biocon Insulin N and Humulin® N

Healthy Volunteer Clinical Trial

Official title:

A Randomised, Double-blind, Three-period, Partially Replicated Crossover, Euglycaemic Glucose Clamp Study in Healthy Volunteers to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity of Biocon Insulin N and Humulin® N

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04022304
• Other study ID #: EQN
• Status: Completed
• Phase: Phase 1
• Start date: June 15, 2019
• Est. completion date: December 27, 2019

Study information

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

Clinical Trial Summary

Single-centre, randomised, double-blind, three-period, six-sequence, partially replicated design, crossover trial in healthy subjects

Description:

The present study is designed to demonstrate pharmacokinetic and pharmacodynamic equivalence of Biocon Insulin N with Humulin® N in healthy subjects.

The treatment consists of one single dose of the test or reference product, administered during each of the three study periods, separated by 5-7 days between each dosing. The planned trial duration for each subject is about 17 to 43 days. Eligible subjects will undergo three euglycaemic clamp examinations (each of 24 hours duration).

Depending on the sequence in which a particular subject is randomized, each subject will either undergo two clamps with administration of test product plus one clamp with administration of reference product, or, two clamps with administration of reference product plus one clamp with administration of test product, in random order.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: December 27, 2019
• Est. primary completion date: December 21, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy male and post-menopausal female subjects. Post-menopausal defined as 12 months of no menses without an alternative medical cause and confirmed by a follicle stimulating hormone (FSH) level in the post-menopausal range (>= 25.8 IU/L).

2. Age between 18 and 55 years, both inclusive

3. Body mass index between 18.5 and 29.0 kg/m^2, both inclusive.

4. Fasting plasma glucose concentration <= 100 mg/dl.

5. Considered generally healthy upon completion of medical history and screening safety assessments, as judged by the Investigator.

Exclusion Criteria:

1. Known or suspected hypersensitivity to Investigational Medicinal products (IMP(s)) or related products.

2. 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).

3. Pulse rate at rest outside the range of 50-90 beats per minute.

4. Receipt of any medicinal product in clinical development within 30 days or five times its half-life (whichever is longer) before randomisation.

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Biological:
• Biocon Insulin N
Biocon Insulin N is an intermediate-acting isophane suspension of human insulin produced by recombinant deoxyribonucleic acid(rDNA) technology utilizing Pichia pastoris (yeast).
• Humulin® N
Humulin® N (human insulin [recombinant deoxyribonucleic acid origin] isophane suspension) is an intermediate-acting human isophane insulin. Humulin® N is a suspension of crystals produced from combining human insulin and protamine sulphate.

Locations

Country	Name	City	State
Germany	Profil Institut für Stoffwechselforschung GmbH	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 endpoint: Number of subjects with Adverse Events (AEs), clinically significant changes in Physical examination, Vital signs. Local tolerability/ Injection site reactions	Number of subjects with Adverse Events (AEs), clinically significant changes in Physical examination, Vital signs.; Local tolerability/ Injection site reactions	First dose to followup period (Total duration: 21 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: 42 days approximate)
Primary	Primary PK endpoint: area under the insulin concentration curve(AUCins).0-24h	area under the insulin concentration curve	0-24hour
Primary	Primary PK endpoint: maximum observed insulin concentration(Cins.max)	maximum observed insulin concentration	0-24hour
Primary	PD endpoint:area under the glucose infusion rate curve(AUCGIR)0-24h	area under the glucose infusion rate curve	0-24hour
Primary	PD endpoint:maximum observed glucose infusion rate (GIRmax)	maximum observed glucose infusion rate	0-24hour
Secondary	Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).0-infinity	area under the insulin concentration-time curve	0-24 hours
Secondary	Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).0-12h	area under the insulin concentration-time curve	0-12hour
Secondary	Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).12-24h	area under the insulin concentration-time curve	12-24hour
Secondary	Secondary PK endpoint:time to maximum observed insulin concentration (tmax.ins)	time to maximum observed insulin concentration	0-24 hours
Secondary	Secondary PK endpoint:terminal elimination rate constant of insulin (?z)	terminal elimination rate constant of insulin	0-24 hours
Secondary	Secondary PK endpoint: terminal elimination half-life (t½)	terminal elimination half-life calculated as t½=ln2/?z	0-24 hours
Secondary	Secondary PK endpoint: time(t)50%-INS(early)	time to half-maximum before Cmax	0-24 hours
Secondary	Secondary PK endpoint: time(t)50%-INS(late)	time to half-maximum after Cmax	0-24 hours
Secondary	Secondary PD endpoint: areas under the glucose infusion rate curve(AUCGIR).0-12h	areas under the glucose infusion rate curve	0-12hours
Secondary	Secondary PD endpoint: areas under the glucose infusion rate curve(AUCGIR).12-24h	areas under the glucose infusion rate curve	12-24hours
Secondary	Secondary PD endpoint: time to maximum glucose infusion rate(tmax.GIR)	time to maximum glucose infusion rate	0-24 hours
Secondary	Secondary PD endpoint:time to half-maximum glucose infusion rate before GIRmax (tGIR.50%-early)	time to half-maximum glucose infusion rate before GIRmax	0-24 hours
Secondary	Secondary PD endpoint: time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late)	time to half-maximum glucose infusion rate after GIRmax	0-24 hours
Secondary	Secondary PD endpoint: 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))	0-24 hours