Clinical trial NCT05413863: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Recombinant Human INsulin Equivalence-4
RHINE-4
Pharmacokinetic
Pharmacodynamic
Biocon's Insulin R U-500
Humulin® R U-500
Lead sponsor: Biocon Limited
Sponsor class: INDUSTRY
Collaborators: name: Profil Institut für Stoffwechselforschung GmbH
First posted: 2022-06-10
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Partially replicated design, crossover trial
Primary purpose: OTHER

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Primary pharmacokinetics (PK) endpoint: area under the insulin concentration curve(AUCins).0-12h
timeFrame: 0 to12 hours
measure: Primary pharmacokinetics (PK) endpoint: maximum observed insulin concentration(Cins.max)
timeFrame: NAP (Not Applicable)
measure: Primary pharmacodynamics (PD) endpoint:area under the glucose infusion rate curve (AUCGIR)0-12h
timeFrame: 0 to 12 hours
measure: Primary pharmacodynamics (PD) endpoint:maximum observed glucose infusion rate (GIRmax)
timeFrame: NAP (Not Applicable)
Secondary outcomes:
measure: Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve(AUCins).0-infinity
timeFrame: 0 hours to 24 hours
measure: Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve(AUCins).0-24h
timeFrame: 0 to 24 hours
measure: Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve (AUCins).12-24h
timeFrame: 12 to 24 hours
measure: Secondary pharmacokinetics (PK) endpoint:time to maximum observed insulin concentration (tmax.ins)
timeFrame: 0 to 24 hours
measure: Secondary pharmacokinetics (PK) endpoint:terminal elimination rate constant of insulin (λz)
timeFrame: 0 to 24 hours
measure: Secondary pharmacokinetics (PK) endpoint: terminal elimination half-life (t½)
timeFrame: 0 to 24 hours
measure: Secondary pharmacokinetics (PK) endpoint: time(t)50%-Insulin (INS)(early)
timeFrame: 0 to 24 hours
measure: Secondary pharmacokinetics (PK) endpoint: time(t) 50%-Insulin (INS)(late)
timeFrame: 0 to 24 hours
measure: Secondary pharmacodynamics (PD) endpoint: areas under the glucose infusion rate curve(AUCGIR).0-24h
timeFrame: 0 to 24 hours
measure: Secondary pharmacodynamics (PD) endpoint: areas under the glucose infusion rate curve(AUCGIR).12-24h
timeFrame: 12 to 24 hours
measure: Secondary pharmacodynamics (PD) endpoint: time to maximum glucose infusion rate(tmax.GIR)
timeFrame: 0 to 24 hours
measure: Secondary pharmacodynamics (PD) endpoint:time to half-maximum glucose infusion rate before GIRmax (tGIR.50%-early)
timeFrame: 0 to 24 hours
measure: Secondary pharmacodynamics (PD) endpoint: time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late)
timeFrame: 0 to 24 hours
measure: 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,
timeFrame: 0 to 24 hours
Other outcomes:
measure: Safety endpoint: Number of subjects with Adverse Events (AEs)
timeFrame: Signing of Informed consent form (ICF) to follow-up period (Total duration: 44 days approximate)
measure: Safety endpoint: Number of subjects with Clinically significant changes in Physical examination
timeFrame: Signing of Informed consent form (ICF) to follow-up period (Total duration: 44 days approximate)
measure: Safety endpoint: Number of subjects with Clinically significant changes in Vital signs
timeFrame: Signing of Informed consent form (ICF) to follow-up period (Total duration: 44 days approximate)
measure: Safety endpoint: Local tolerability assessment / Injection site reactions
timeFrame: Signing of Informed consent form (ICF) to follow-up period (Total duration:44 days approximate)
measure: Safety endpoint: Number of subjects with clinically significant changes in Laboratory safety parameters
timeFrame: Signing of Informed consent form (ICF) to follow-up period (Total duration:44 days approximate)
measure: Safety endpoint: Number of subjects with clinically significant changes in ECG
timeFrame: Signing of Informed consent form (ICF) to follow-up period (Total duration:44 days approximate)
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH 9
Study officials:
affiliation: Profil Institut für Stoffwechselforschung GmbH
name: Dr Ulrike Hövelmann, MD
role: PRINCIPAL_INVESTIGATOR
References: