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

Phase 1
Completed
Conditions
Healthy Volunteer
Interventions
Biological: Biocon Insulin N
Biological: Humulin® N
Registration Number
NCT04022304
Lead Sponsor
Biocon Limited
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
90
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sequence: Biocon Insulin N- Humulin® N- Humulin® NBiocon Insulin NPeriod 1: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Humulin® N(100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Biocon Insulin N- Biocon Insulin N-Humulin® NBiocon Insulin NPeriod 1: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Humulin® N- Humulin® N-Biocon Insulin NBiocon Insulin NPeriod 1: 0.4 IU/kg of Humulin® N(100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Biocon Insulin N- Humulin® N- Biocon Insulin NHumulin® NPeriod 1: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Humulin® N-Biocon Insulin N- Biocon Insulin NHumulin® NPeriod 1: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Humulin® N- Biocon Insulin N-Humulin® NBiocon Insulin NPeriod 1: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Biocon Insulin N- Humulin® N- Humulin® NHumulin® NPeriod 1: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Humulin® N(100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Humulin® N- Humulin® N-Biocon Insulin NHumulin® NPeriod 1: 0.4 IU/kg of Humulin® N(100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Biocon Insulin N- Humulin® N- Biocon Insulin NBiocon Insulin NPeriod 1: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Humulin® N-Biocon Insulin N- Biocon Insulin NBiocon Insulin NPeriod 1: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Humulin® N- Biocon Insulin N-Humulin® NHumulin® NPeriod 1: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Sequence: Biocon Insulin N- Biocon Insulin N-Humulin® NHumulin® NPeriod 1: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 2: 0.4 IU/kg of Biocon Insulin N (100 IU/mL) administered once subcutaneously. Period 3: 0.4 IU/kg of Humulin® N (100 IU/mL) administered once subcutaneously. The treatment periods will be separated by 5-7 days
Primary Outcome Measures
NameTimeMethod
Primary PK endpoint: maximum observed insulin concentration(Cins.max)0-24hour

maximum observed insulin concentration

Primary PK endpoint: area under the insulin concentration curve(AUCins).0-24h0-24hour

area under the insulin concentration curve

PD endpoint:area under the glucose infusion rate curve(AUCGIR)0-24h0-24hour

area under the glucose infusion rate curve

PD endpoint:maximum observed glucose infusion rate (GIRmax)0-24hour

maximum observed glucose infusion rate

Secondary Outcome Measures
NameTimeMethod
Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).12-24h12-24hour

area under the insulin concentration-time curve

Secondary PK endpoint: time(t)50%-INS(late)0-24 hours

time to half-maximum after Cmax

Secondary PD endpoint: Onset of action0-24 hours

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))

Secondary PK endpoint: terminal elimination half-life (t½)0-24 hours

terminal elimination half-life calculated as t½=ln2/λz

Secondary PK endpoint: time(t)50%-INS(early)0-24 hours

time to half-maximum before Cmax

Secondary PD endpoint: areas under the glucose infusion rate curve(AUCGIR).12-24h12-24hours

areas under the glucose infusion rate curve

Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).0-infinity0-24 hours

area under the insulin concentration-time curve

Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).0-12h0-12hour

area under the insulin concentration-time curve

Secondary PK endpoint:time to maximum observed insulin concentration (tmax.ins)0-24 hours

time to maximum observed insulin concentration

Secondary PD endpoint: time to maximum glucose infusion rate(tmax.GIR)0-24 hours

time to maximum glucose infusion rate

Secondary PD endpoint:time to half-maximum glucose infusion rate before GIRmax (tGIR.50%-early)0-24 hours

time to half-maximum glucose infusion rate before GIRmax

Secondary PD endpoint: time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late)0-24 hours

time to half-maximum glucose infusion rate after GIRmax

Secondary PK endpoint:terminal elimination rate constant of insulin (λz)0-24 hours

terminal elimination rate constant of insulin

Secondary PD endpoint: areas under the glucose infusion rate curve(AUCGIR).0-12h0-12hours

areas under the glucose infusion rate curve

Trial Locations

Locations (1)

Profil Institut für Stoffwechselforschung GmbH

🇩🇪

Neuss, Germany

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