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

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ClinicalTrials.gov Identifier: NCT04022304
Recruitment Status : Recruiting
First Posted : July 17, 2019
Last Update Posted : July 17, 2019
Sponsor:
Collaborator:
Profil Institut für Stoffwechselforschung GmbH
Information provided by (Responsible Party):
Biocon Limited

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

Condition or disease Intervention/treatment Phase
Healthy Volunteer Biological: Biocon Insulin N Biological: Humulin® N Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Partially replicated design, crossover trial
Masking: Double (Participant, Investigator)
Masking Description: Double blind study
Primary Purpose: Other
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
Actual Study Start Date : June 15, 2019
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sequence: Humulin® N- Biocon Insulin N-Humulin® N

Period 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

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).

Biological: 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.

Experimental: Sequence: Biocon Insulin N- Humulin® N- Humulin® N

Period 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

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).

Biological: 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.

Experimental: Sequence: Humulin® N- Humulin® N-Biocon Insulin N

Period 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

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).

Biological: 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.

Experimental: Sequence: Biocon Insulin N- Humulin® N- Biocon Insulin N

Period 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

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).

Biological: 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.

Experimental: Sequence: Humulin® N-Biocon Insulin N- Biocon Insulin N

Period 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

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).

Biological: 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.

Experimental: Sequence: Biocon Insulin N- Biocon Insulin N-Humulin® N

Period 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

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).

Biological: 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.




Primary Outcome Measures :
  1. Primary PK endpoint: area under the insulin concentration curve(AUCins).0-24h [ Time Frame: 0-24hour ]
    area under the insulin concentration curve

  2. Primary PK endpoint: maximum observed insulin concentration(Cins.max) [ Time Frame: 0-24hour ]
    maximum observed insulin concentration

  3. PD endpoint:area under the glucose infusion rate curve(AUCGIR)0-24h [ Time Frame: 0-24hour ]
    area under the glucose infusion rate curve

  4. PD endpoint:maximum observed glucose infusion rate (GIRmax) [ Time Frame: 0-24hour ]
    maximum observed glucose infusion rate


Secondary Outcome Measures :
  1. Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).0-infinity [ Time Frame: 0-24 hours ]
    area under the insulin concentration-time curve

  2. Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).0-12h [ Time Frame: 0-12hour ]
    area under the insulin concentration-time curve

  3. Secondary PK endpoint: area under the insulin concentration-time curve(AUCins).12-24h [ Time Frame: 12-24hour ]
    area under the insulin concentration-time curve

  4. Secondary PK endpoint:time to maximum observed insulin concentration (tmax.ins) [ Time Frame: 0-24 hours ]
    time to maximum observed insulin concentration

  5. Secondary PK endpoint:terminal elimination rate constant of insulin (λz) [ Time Frame: 0-24 hours ]
    terminal elimination rate constant of insulin

  6. Secondary PK endpoint: terminal elimination half-life (t½) [ Time Frame: 0-24 hours ]
    terminal elimination half-life calculated as t½=ln2/λz

  7. Secondary PK endpoint: time(t)50%-INS(early) [ Time Frame: 0-24 hours ]
    time to half-maximum before Cmax

  8. Secondary PK endpoint: time(t)50%-INS(late) [ Time Frame: 0-24 hours ]
    time to half-maximum after Cmax

  9. Secondary PD endpoint: areas under the glucose infusion rate curve(AUCGIR).0-12h [ Time Frame: 0-12hours ]
    areas under the glucose infusion rate curve

  10. Secondary PD endpoint: areas under the glucose infusion rate curve(AUCGIR).12-24h [ Time Frame: 12-24hours ]
    areas under the glucose infusion rate curve

  11. Secondary PD endpoint: time to maximum glucose infusion rate(tmax.GIR) [ Time Frame: 0-24 hours ]
    time to maximum glucose infusion rate

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

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

  14. Secondary PD endpoint: Onset of action [ Time Frame: 0-24 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))


Other Outcome Measures:
  1. Safety endpoint: Number of subjects with Adverse Events (AEs), clinically significant changes in Physical examination, Vital signs. Local tolerability/ Injection site reactions [ Time Frame: First dose to followup period (Total duration: 21 days approximate) ]

    Number of subjects with Adverse Events (AEs), clinically significant changes in Physical examination, Vital signs.

    Local tolerability/ Injection site reactions


  2. Safety endpoint: Number of subjects with clinically significant changes in Laboratory safety parameters, Electrocardiogram (ECG) [ Time Frame: Screening and Follow-up period (Total duration: 42 days approximate) ]

    Number of subjects with clinically significant changes in Laboratory safety parameters.

    Number of subjects with clinically significant changes in Electrocardiogram (ECG)




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04022304


Contacts
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Contact: Dr Gursharan Singh +91 080 2808 ext 2808 gursharan.singh@biocon.com
Contact: Jayanti Panda +91 80 2808 ext 5304 Jayanti.Panda@biocon.com

Locations
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Germany
Profil Institut für Stoffwechselforschung GmbH Recruiting
Neuss, Germany
Contact: Grit Andersen, M.D         
Sponsors and Collaborators
Biocon Limited
Profil Institut für Stoffwechselforschung GmbH
Investigators
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Principal Investigator: Dr. Grit Andersen Profil Institut für Stoffwechselforschung GmbH Hellersbergstraße 9]

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Responsible Party: Biocon Limited
ClinicalTrials.gov Identifier: NCT04022304     History of Changes
Other Study ID Numbers: EQN
First Posted: July 17, 2019    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Biocon Limited:
Recombinant Human Insulin N (rhi N)
Additional relevant MeSH terms:
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Insulin
Insulin, Globin Zinc
Insulin, Isophane
Isophane Insulin, Human
Isophane insulin, beef
Hypoglycemic Agents
Physiological Effects of Drugs