Clinical trial NCT04022304: Comparision of Pharmacokinetic and Pharmacodynamic of Biocon Insulin N and Humulin® N
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: Recombinant Human Insulin N (rhi N)
Lead sponsor: Biocon Limited
Sponsor class: INDUSTRY
Collaborators: name: Profil Institut für Stoffwechselforschung GmbH
First posted: 2019-07-17
Enrollment: 90
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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Primary PK endpoint: area under the insulin concentration curve(AUCins).0-24h
timeFrame: 0-24hour
measure: Primary PK endpoint: maximum observed insulin concentration(Cins.max)
timeFrame: 0-24hour
measure: PD endpoint:area under the glucose infusion rate curve(AUCGIR)0-24h
timeFrame: 0-24hour
measure: PD endpoint:maximum observed glucose infusion rate (GIRmax)
timeFrame: 0-24hour
Secondary outcomes:
measure: Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).0-infinity
timeFrame: 0-24 hours
measure: Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).0-12h
timeFrame: 0-12hour
measure: Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).12-24h
timeFrame: 12-24hour
measure: Secondary PK endpoint:time to maximum observed insulin concentration (tmax.ins)
timeFrame: 0-24 hours
measure: Secondary PK endpoint:terminal elimination rate constant of insulin (λz)
timeFrame: 0-24 hours
measure: Secondary PK endpoint: terminal elimination half-life (t½)
timeFrame: 0-24 hours
measure: Secondary PK endpoint: time(t)50%-INS(early)
timeFrame: 0-24 hours
measure: Secondary PK endpoint: time(t)50%-INS(late)
timeFrame: 0-24 hours
measure: Secondary PD endpoint: areas under the glucose infusion rate curve(AUCGIR).0-12h
timeFrame: 0-12hours
measure: Secondary PD endpoint: areas under the glucose infusion rate curve(AUCGIR).12-24h
timeFrame: 12-24hours
measure: Secondary PD endpoint: time to maximum glucose infusion rate(tmax.GIR)
timeFrame: 0-24 hours
measure: Secondary PD endpoint:time to half-maximum glucose infusion rate before GIRmax (tGIR.50%-early)
timeFrame: 0-24 hours
measure: Secondary PD endpoint: time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late)
timeFrame: 0-24 hours
measure: Secondary PD endpoint: Onset of action
timeFrame: 0-24 hours
Other outcomes:
measure: Safety endpoint: Number of subjects with Adverse Events (AEs), clinically significant changes in Physical examination, Vital signs. Local tolerability/ Injection site reactions
timeFrame: First dose to followup period (Total duration: 21 days approximate)
measure: Safety endpoint: Number of subjects with clinically significant changes in Laboratory safety parameters, Electrocardiogram (ECG)
timeFrame: Screening and Follow-up period (Total duration: 42 days approximate)
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Profil Institut für Stoffwechselforschung GmbH Hellersbergstraße 9]
name: Dr. Grit Andersen
role: PRINCIPAL_INVESTIGATOR
References: