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出境医 / 临床实验 / Comparision of Pharmacokinetics(PK) and Pharmacodynamics(PD) of Biocon Insulin R and Humulin® R

Comparision of Pharmacokinetics(PK) and Pharmacodynamics(PD) of Biocon Insulin R and Humulin® R

Study Description
Brief Summary:
Single-centre, randomised, double-blind, single dose, two-treatment, two-period, two sequence, crossover,12-hour euglycaemic glucose clamp trial in healthy subjects

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

Detailed Description:

The present study is designed to demonstrate pharmacokinetic and pharmacodynamic equivalence of Biocon Insulin R with Humulin® R in healthy subjects.

The treatment consists of one single dose of the test or reference product, administered during each of the two study periods, separated by 5-7 days between each dosing.

The planned trial duration for each subject is about 12 to 36 days. Eligible subjects will undergo two 12-hour euglycaemic clamp examinations, one after administration of the test product and one after administration of the reference product in random order.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double-blind
Primary Purpose: Other
Official Title: A Randomised, Double-blind, Two-period Crossover, Euglycaemic Glucose Clamp Study in Healthy Volunteers to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity of Biocon Insulin R and Humulin® R
Actual Study Start Date : June 18, 2019
Actual Primary Completion Date : September 15, 2019
Actual Study Completion Date : September 20, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: Biocon Insulin R
0.3 IU/kg Dose per administration, subcutaneous Route of administration
 Biological: Biocon Insulin R
Biocon Insulin R is a short-acting human insulin, produced by recombinant deoxyribonucleic acid (rDNA) technology utilizing Pichia pastoris (yeast).
Active Comparator: Humulin® R (regular insulin human)
0.3 IU/kg Dose per administration, subcutaneous Route of administration
 Biological: Humulin®R
Humulin® R is a polypeptide hormone structurally identical to human insulin synthesised through recombinant deoxyribonucleic acid (rDNA) technology in a non-pathogenic laboratory strain of Escherichia coli bacteria.
Outcome Measures
Primary Outcome Measures :
  1. PK endpoints:Area under the insulin concentration curve(AUCins).0-12h [ Time Frame: 0-12 hours ]
    Area under the insulin concentration curve from 0 to 12 hours.

  2. PD endpoints: Area under the glucose infusion rate curve(AUCGIR).0-12h [ Time Frame: 0-12 hours ]
    Area under the glucose infusion rate curve

  3. PK endpoints: Maximum observed insulin concentration(Cins.max) [ Time Frame: 0-12 hours ]
    Maximum observed insulin concentration

  4. PD endpoints:maximum glucose infusion rate(GIRmax) [ Time Frame: 0-12 hours ]
    maximum glucose infusion rate


Secondary Outcome Measures :
  1. PK endpoint- Area under the insulin concentration curve(AUCins).0-2h [ Time Frame: 0 to 2 hours ]
    Area under the insulin concentration curve

  2. PK endpoint- Area under the insulin concentration curve(AUCins).0-6h [ Time Frame: 0 to 6 hours ]
    area under the insulin concentration curve

  3. PK endpoint- Area under the insulin concentration curve(AUCins).6-12h [ Time Frame: 6 to 12 hours ]
    area under the insulin concentration curve

  4. PK endpoint- Area under the insulin concentration curve(AUCins).0-infinity [ Time Frame: 0 hours to 24 hours ]
    area under the insulin concentration-time curve

  5. PK endpoint- time to maximum concentration( tmax) [ Time Frame: 0-12 hours ]
    time to maximum observed insulin concentration.

  6. PK endpoint- time(t)50%-ins(early) [ Time Frame: 0-12 hours ]
    time to half-maximum before Cins.max.

  7. PK endpoint- time(t)50%-ins(late) [ Time Frame: 0-12 hours ]
    time to half-maximum after Cins.max.

  8. PK endpoint- terminal elimination half-life (t½) [ Time Frame: 0-12 hours ]
    terminal elimination half-life calculated as t½=ln2/λz.

  9. PK endpoint- terminal elimination rate constant (λz) [ Time Frame: 0-12 hours ]
    terminal elimination rate constant of insulin.

  10. PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-2h [ Time Frame: 0 to 2 hours ]
    area under the glucose infusion rate curve

  11. PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-6h [ Time Frame: 0 to 6 hours ]
    area under the glucose infusion rate curve

  12. PD endpoint: area under the glucose infusion rate curve(AUCGIR).6-12h [ Time Frame: 6 to 12 hours ]
    area under the glucose infusion rate curve

  13. PD endpoint: time to maximum glucose infusion rate (tGIR.max) [ Time Frame: 0-12 hours ]
    time to maximum glucose infusion rate

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

  15. PD endpoint:time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late) [ Time Frame: 0-12 hours ]
    time to half-maximum glucose infusion rate after Maximum glucose infusion rate(GIRmax)

  16. PD endpoint: Onset of action [ Time Frame: 0-12 hours ]
    ime 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 endpoints: Number of subjects with Adverse Events, clinically significant changes in Physical examination, Vital signs. Local tolerability/ Injection site reactions [ Time Frame: First dose to followup period (Total duration: 14 days approximate) ]

    Number of subjects with Adverse Events, 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 to Follow-up period (Total duration: 35 days approximate) ]

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

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



Eligibility Criteria
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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:

  • Healthy male or post-menopausal female subject. 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/m^2, both inclusive.
  • Fasting plasma glucose concentration <= 100 mg/dL.
  • Considered generally healthy upon completion of medical history and screening safety assessments, as judged by the Investigator

Exclusion Criteria:

  • Known or suspected hypersensitivity to Investigational Medicinal products (IMP(s)) 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.
  • Any history or presence of clinically relevant comorbidity, as judged by the investigator.
  • 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).
  • Pulse rate at rest outside the range of 50-90 beats per minute.
Contacts and Locations

Locations
Layout table for location information
Germany
Profil Mainz GmbH
Mainz, Germany
Sponsors and Collaborators
Biocon Limited
Profil Institut für Stoffwechselforschung GmbH
Investigators
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Principal Investigator: Dr. Leona P Mörschel Profil Mainz GmbH
Tracking Information
First Submitted Date  ICMJE June 29, 2019
First Posted Date  ICMJE July 17, 2019
Last Update Posted Date January 30, 2020
Actual Study Start Date  ICMJE June 18, 2019
Actual Primary Completion Date September 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 13, 2019)
  • PK endpoints:Area under the insulin concentration curve(AUCins).0-12h [ Time Frame: 0-12 hours ]
    Area under the insulin concentration curve from 0 to 12 hours.
  • PD endpoints: Area under the glucose infusion rate curve(AUCGIR).0-12h [ Time Frame: 0-12 hours ]
    Area under the glucose infusion rate curve
  • PK endpoints: Maximum observed insulin concentration(Cins.max) [ Time Frame: 0-12 hours ]
    Maximum observed insulin concentration
  • PD endpoints:maximum glucose infusion rate(GIRmax) [ Time Frame: 0-12 hours ]
    maximum glucose infusion rate
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2019)
  • PK endpoint- Area under the insulin concentration curve(AUCins).0-2h [ Time Frame: 0 to 2 hours ]
    Area under the insulin concentration curve
  • PK endpoint- Area under the insulin concentration curve(AUCins).0-6h [ Time Frame: 0 to 6 hours ]
    area under the insulin concentration curve
  • PK endpoint- Area under the insulin concentration curve(AUCins).6-12h [ Time Frame: 6 to 12 hours ]
    area under the insulin concentration curve
  • PK endpoint- Area under the insulin concentration curve(AUCins).0-infinity [ Time Frame: 0 hours to 24 hours ]
    area under the insulin concentration-time curve
  • PK endpoint- time to maximum concentration( tmax) [ Time Frame: 0-12 hours ]
    time to maximum observed insulin concentration.
  • PK endpoint- time(t)50%-ins(early) [ Time Frame: 0-12 hours ]
    time to half-maximum before Cins.max.
  • PK endpoint- time(t)50%-ins(late) [ Time Frame: 0-12 hours ]
    time to half-maximum after Cins.max.
  • PK endpoint- terminal elimination half-life (t½) [ Time Frame: 0-12 hours ]
    terminal elimination half-life calculated as t½=ln2/λz.
  • PK endpoint- terminal elimination rate constant (λz) [ Time Frame: 0-12 hours ]
    terminal elimination rate constant of insulin.
  • PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-2h [ Time Frame: 0 to 2 hours ]
    area under the glucose infusion rate curve
  • PD endpoint: area under the glucose infusion rate curve(AUCGIR).0-6h [ Time Frame: 0 to 6 hours ]
    area under the glucose infusion rate curve
  • PD endpoint: area under the glucose infusion rate curve(AUCGIR).6-12h [ Time Frame: 6 to 12 hours ]
    area under the glucose infusion rate curve
  • PD endpoint: time to maximum glucose infusion rate (tGIR.max) [ Time Frame: 0-12 hours ]
    time to maximum glucose infusion rate
  • PD endpoint: time to half-maximum glucose infusion rate before GIRmax (tGIR,50%-early [ Time Frame: 0-12 hours ]
    time to half-maximum glucose infusion rate before GIRmax
  • PD endpoint:time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late) [ Time Frame: 0-12 hours ]
    time to half-maximum glucose infusion rate after Maximum glucose infusion rate(GIRmax)
  • PD endpoint: Onset of action [ Time Frame: 0-12 hours ]
    ime 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 13, 2019)
  • Safety endpoints: Number of subjects with Adverse Events, clinically significant changes in Physical examination, Vital signs. Local tolerability/ Injection site reactions [ Time Frame: First dose to followup period (Total duration: 14 days approximate) ]
    Number of subjects with Adverse Events, clinically significant changes in Physical examination, Vital signs Local tolerability/ Injection site reactions
  • Safety endpoint: Number of subjects with clinically significant changes in Laboratory safety parameters, Electrocardiogram (ECG) [ Time Frame: Screening to Follow-up period (Total duration: 35 days approximate) ]
    Number of subjects with clinically significant changes in Laboratory safety parameters. Number of subjects with clinically significant changes in Electrocardiogram (ECG)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Comparision of Pharmacokinetics(PK) and Pharmacodynamics(PD) of Biocon Insulin R and Humulin® R
Official Title  ICMJE A Randomised, Double-blind, Two-period Crossover, Euglycaemic Glucose Clamp Study in Healthy Volunteers to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity of Biocon Insulin R and Humulin® R
Brief Summary Single-centre, randomised, double-blind, single dose, two-treatment, two-period, two sequence, crossover,12-hour euglycaemic glucose clamp trial in healthy subjects
Detailed Description

The present study is designed to demonstrate pharmacokinetic and pharmacodynamic equivalence of Biocon Insulin R with Humulin® R in healthy subjects.

The treatment consists of one single dose of the test or reference product, administered during each of the two study periods, separated by 5-7 days between each dosing.

The planned trial duration for each subject is about 12 to 36 days. Eligible subjects will undergo two 12-hour euglycaemic clamp examinations, one after administration of the test product and one after administration of the reference product in random order.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Masking Description:
Double-blind
Primary Purpose: Other
Condition  ICMJE Healthy Volunteer
Intervention  ICMJE
  • Biological: Biocon Insulin R
    Biocon Insulin R is a short-acting human insulin, produced by recombinant deoxyribonucleic acid (rDNA) technology utilizing Pichia pastoris (yeast).
  • Biological: Humulin®R
    Humulin® R is a polypeptide hormone structurally identical to human insulin synthesised through recombinant deoxyribonucleic acid (rDNA) technology in a non-pathogenic laboratory strain of Escherichia coli bacteria.
Study Arms  ICMJE
  • Experimental: Biocon Insulin R
    0.3 IU/kg Dose per administration, subcutaneous Route of administration
    Intervention: Biological: Biocon Insulin R
  • Active Comparator: Humulin® R (regular insulin human)
    0.3 IU/kg Dose per administration, subcutaneous Route of administration
    Intervention: Biological: Humulin®R
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 13, 2019) 		42
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 20, 2019
Actual Primary Completion Date September 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy male or post-menopausal female subject. 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/m^2, both inclusive.
  • Fasting plasma glucose concentration <= 100 mg/dL.
  • Considered generally healthy upon completion of medical history and screening safety assessments, as judged by the Investigator

Exclusion Criteria:

  • Known or suspected hypersensitivity to Investigational Medicinal products (IMP(s)) 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.
  • Any history or presence of clinically relevant comorbidity, as judged by the investigator.
  • 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).
  • Pulse rate at rest outside the range of 50-90 beats per minute.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04022317
Other Study ID Numbers  ICMJE EQR
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Biocon Limited
Study Sponsor  ICMJE Biocon Limited
Collaborators  ICMJE Profil Institut für Stoffwechselforschung GmbH
Investigators  ICMJE
Principal Investigator: Dr. Leona P Mörschel Profil Mainz GmbH
PRS Account Biocon Limited
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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