Comparison of the Pharmacokinetic and Pharmacodynamic Properties of Biocon's Insulin R U-500 With Humulin® R U-500 (US Reference Product) in Healthy Subjects

Healthy Volunteers Clinical Trial

— RHINE-4  

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's Human Insulin R U-500 and Humulin® R U-500 (RHINE-4: Recombinant Human INsulin Equivalence-4)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05413863
• Other study ID #: BIO-INS500-101
• Status: Completed
• Phase: Phase 1
• Start date: May 30, 2022
• Est. completion date: December 12, 2022

Study information

• Verified date: May 2023
• 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's Human Insulin R U-500 with Humulin® R U-500 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 18 to 44 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: 78
• Est. completion date: December 12, 2022
• Est. primary completion date: December 12, 2022
• 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. The 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/m2, both inclusive.
• Fasting plasma glucose concentration = 100 mg/dL.
• Considered generally healthy upon completing the medical history and screening safety assessments, as judged by the Investigator.

Exclusion Criteria:

• Known or suspected hypersensitivity to investigational medicinal products (IMPs) 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.
• Systolic blood pressure < 90 mmHg or > 139 mmHg and/or diastolic blood pressure < 50 mmHg or > 89 mmHg after resting for at least 5 minutes in the 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 Volunteers

Intervention

Biological:
• Biocon's Human Insulin R U-500
Biocon's Human Insulin R U-500 (Insulin Human Injection 500 units/mL), 3 mL cartridges (containing 1,500 units of insulin).
• Humulin® R U-500 (US Reference Product)
Humulin® R U-500 (US Reference Product), 3 mL single-patient-use KwikPen® (containing 1,500 units of insulin)

Locations

Country	Name	City	State
Germany	Profil Institut für Stoffwechselforschung GmbH 9	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)		Signing of Informed consent form (ICF) to follow-up period (Total duration: 44 days approximate)
Other	Safety endpoint: Number of subjects with Clinically significant changes in Physical examination		Signing of Informed consent form (ICF) to follow-up period (Total duration: 44 days approximate)
Other	Safety endpoint: Number of subjects with Clinically significant changes in Vital signs		Signing of Informed consent form (ICF) to follow-up period (Total duration: 44 days approximate)
Other	Safety endpoint: Local tolerability assessment / Injection site reactions	Number of subjects with Injection Site Reactions	Signing of Informed consent form (ICF) to follow-up period (Total duration:44 days approximate)
Other	Safety endpoint: Number of subjects with clinically significant changes in Laboratory safety parameters		Signing of Informed consent form (ICF) to follow-up period (Total duration:44 days approximate)
Other	Safety endpoint: Number of subjects with clinically significant changes in ECG		Signing of Informed consent form (ICF) to follow-up period (Total duration:44 days approximate)
Primary	Primary pharmacokinetics (PK) endpoint: area under the insulin concentration curve(AUCins).0-12h	Area under the insulin concentration curve	0 to12 hours
Primary	Primary pharmacokinetics (PK) endpoint: maximum observed insulin concentration(Cins.max)	Maximum observed insulin concentration	NAP (Not Applicable)
Primary	Primary pharmacodynamics (PD) endpoint:area under the glucose infusion rate curve (AUCGIR)0-12h	Area under the glucose infusion rate curve	0 to 12 hours
Primary	Primary pharmacodynamics (PD) endpoint:maximum observed glucose infusion rate (GIRmax)	Maximum observed glucose infusion rate	NAP (Not Applicable)
Secondary	Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve(AUCins).0-infinity	Area under the insulin concentration-time curve	0 hours to 24 hours
Secondary	Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve(AUCins).0-24h	Area under the insulin concentration-time curve	0 to 24 hours
Secondary	Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve (AUCins).12-24h	Area under the insulin concentration-time curve	12 to 24 hours
Secondary	Secondary pharmacokinetics (PK) endpoint:time to maximum observed insulin concentration (tmax.ins)	Time to maximum observed insulin concentration	0 to 24 hours
Secondary	Secondary pharmacokinetics (PK) endpoint:terminal elimination rate constant of insulin (?z)	Terminal elimination rate constant of insulin	0 to 24 hours
Secondary	Secondary pharmacokinetics (PK) endpoint: terminal elimination half-life (t½)	Terminal elimination half-life calculated	0 to 24 hours
Secondary	Secondary pharmacokinetics (PK) endpoint: time(t)50%-Insulin (INS)(early)	Time to half-maximum before Cmax	0 to 24 hours
Secondary	Secondary pharmacokinetics (PK) endpoint: time(t) 50%-Insulin (INS)(late)	Time to half-maximum after Cmax	0 to 24 hours
Secondary	Secondary pharmacodynamics (PD) endpoint: areas under the glucose infusion rate curve(AUCGIR).0-24h	Area under the glucose infusion rate curve	0 to 24 hours
Secondary	Secondary pharmacodynamics (PD) endpoint: areas under the glucose infusion rate curve(AUCGIR).12-24h	Area under the glucose infusion rate curve	12 to 24 hours
Secondary	Secondary pharmacodynamics (PD) endpoint: time to maximum glucose infusion rate(tmax.GIR)	Time to maximum glucose infusion rate	0 to 24 hours
Secondary	Secondary pharmacodynamics (PD) endpoint:time to half-maximum glucose infusion rate before GIRmax (tGIR.50%-early)	Time to half-maximum glucose infusion rate before GIRmax	0 to 24 hours
Secondary	Secondary pharmacodynamics (PD) endpoint: time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late)	Time to half-maximum glucose infusion rate after GIRmax	0 to 24 hours
Secondary	Secondary pharmacodynamics (PD) endpoint: Onset of action, time from trial product administration until plasma glucose concentration has decreased at least 5 mg/dL from baseline,	Time from trial product administration until plasma glucose concentration	0 to 24 hours