| CTRI Number |
CTRI/2023/07/055238 [Registered on: 14/07/2023] Trial Registered Prospectively |
| Last Modified On: |
20/11/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
|
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
A comparative pharmacokinetic and pharmacodynamic study of
insulin aspart protamine suspension administered as subcutaneous injection in healthy subjects. |
|
Scientific Title of Study
|
A randomized, double blinded, balanced, two treatment, two period, two sequence, cross over, euglycemic clamp study to compare the pharmacokinetic and pharmacodynamic activity of RapilinTM 30 (30% insulin aspart and 70% insulin aspart protamine suspension) injection with NovoMix® 30 (30% insulin aspart and 70% insulin aspart protamine suspension) after single dose subcutaneous injection in healthy human adult male subjects under fasting condition.
|
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 001-23 Version No.1 Dated 16MAR2023 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Basavaprabhu A MBBS MD |
| Designation |
Principal Investigator |
| Affiliation |
Ecron Acunova Limited |
| Address |
KMC Hospital, Attavar,
Mangalore - 575 001, India.
V floor, MCODS Building, KMC Hospital,
Attavar, Mangalore- 575 001, India
Dakshina Kannada
KARNATAKA
575 001
India |
| Phone |
91-824-2445858 |
| Fax |
91-824-2428379 |
| Email |
bachu1504@yahoo.co.in |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Vasudev Shenoy |
| Designation |
Assistant Vice President |
| Affiliation |
Ecron Acunova Limited |
| Address |
Ecron Acunova Limited
V floor, MCODS Building, KMC Hospital,
Attavar, Mangalore- 575 001
Ecron Acunova Limited
V floor, MCODS Building, KMC Hospital,
Attavar, Mangalore- 575 001
Dakshina Kannada
KARNATAKA
575 001
India |
| Phone |
9880599233 |
| Fax |
|
| Email |
vasudev.shenoy@navitaslifesciences.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Vasudev Shenoy |
| Designation |
Assistant Vice President |
| Affiliation |
Ecron Acunova Limited |
| Address |
Ecron Acunova Limited
V floor, MCODS Building, KMC Hospital,
Attavar, Mangalore- 575 001
Ecron Acunova Limited
V floor, MCODS Building, KMC Hospital,
Attavar, Mangalore- 575 001
Dakshina Kannada
KARNATAKA
575 001
India |
| Phone |
9880599233 |
| Fax |
|
| Email |
vasudev.shenoy@navitaslifesciences.com |
|
|
Source of Monetary or Material Support
|
| Mankind Pharma Limited,208, Okhla Industrial Estate,
Phase III, New Delhi, 110020 India.
|
|
|
Primary Sponsor
|
| Name |
Mankind Pharma Limited, India |
| Address |
208, Okhla Industrial Estate,
Phase III, New Delhi – 110020, India |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Basavaprabhu A MBBS MD |
Ecron Acunova Limited |
V floor, MCODS Building, KMC Hospital,
Attavar, Mangalore- 575 001, India
Dakshina Kannada
KARNATAKA |
91-824-2445858
91-824-2428379
bachu1504@yahoo.co.in |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Father Muller Institutional Ethics Committee (FMIEC) |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Healthy Human Volunteers |
Subjects from a pool of healthy volunteers screened within 21 days prior to the study start
will be considered as potential participants in the study.
|
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Human Insulin analog |
NovoMix® 30 (30% insulin aspart and 70% insulin aspart protamine
suspension) of Novo Nordisk, India |
| Intervention |
Human insulin analog |
RapilinTM 30 (30% insulin aspart and 70% insulin aspart protamine
suspension) injection, Manufactured by Gan & Lee Pharmaceuticals, No. 8
Nanfeng West 1st Street, Huoxian, Tongzhou District, Beijing, China |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
45.00 Year(s) |
| Gender |
Both |
| Details |
1. Normal healthy human adult male volunteers aged between 18 -45 years (both
ages inclusive).
2. Volunteer provided written informed consent and are willing to participate in the
study.
3. Volunteer with Body Mass Index of 18.50 to 27.00 Kg/m2
(both inclusive).
4. No evidence of underlying disease during pre-study screening, medical history,
physical examination and laboratory investigations done within 21 days prior to
commencement of the study.
5. Pre-study screening laboratory tests are either normal or within acceptable limits
or are considered by the Investigator to be of no clinical significance with respect
to participation in the study.
6. Negative or non-reactive for antibodies to HIV 1 and 2, hepatitis B & C and RPR.
7. Negative test results for alcohol (in urine or in breath), negative urine drugs of
abuse test.
8. Non-smoker, non-tobacco (in any form) users;
9. 12 lead ECG recording either normal or within acceptable limits or considered by
the Investigator to be of no clinical significance with respect to his participation in
the study.
10. Normal or clinically non - significant chest X-ray (PA) taken within 06 months
before the day of dosing.
11. Available for the entire study and capable of understanding instructions and
communicating with the investigators and clinical study facility staff.
12. Who has not undergone vasectomy, must agree to use condoms, or spermicide to
avoid fathering a child during the course of the study and for a period of 07 days
after the last dose administration of investigational product.
13. Volunteer having Oral Glucose Tolerance Test (OGTT) results showing
within normal or within acceptable limits or as considered by the
Investigator to be of no clinical significance with respect to his participation
in the study.
14. Volunteer having HbA1c: less than or equal to 5.6%.
|
|
| ExclusionCriteria |
| Details |
1. Known allergy to Insulin or any component of the formulation and to any other
related drug.
2. History or presence of significant cardiovascular, respiratory, hepatic, renal,
hematological, gastrointestinal, endocrine, immunologic, dermatologic,
musculoskeletal, neurological or psychiatric disease.
3. History/presence of alcohol abuse or drug abuse.
4. History of smoking, even single cigarette, bidis or any other form.
5. History/presence of asthma.
6. History/presence of urticaria or other allergic type reactions after taking any
medication.
7. History/presence of clinically significant illness within 04 weeks before the start
of the study.
8. History/presence of significant Hypersensitivity to heparin.
9. History of clinically relevant allergy (except for untreated, asymptomatic,
seasonal allergies at time of dosing) or any allergic reactions to any drugs.
10. Scheduled for surgery any time during study or within 07 days after study
completion.
11. History of difficulty in donating blood.
12. With unsuitable veins for repeated venipuncture.
13. Participation in any other clinical or bioequivalence study or otherwise would
have donated in excess of 350 mL of blood in the last 90 days.
14. Consumption of prescription medication or OTC products (including vitamins and
natural products) within 14 days prior to dosing in Period 1, including topical
medication.
15. Hospitalization within 28 days prior to administration of the study medication.
16. History of difficulty in swallowing.
17. Evidence of skin lesions on forearm of signs of vein puncture on the forearm
suggestive of recent donation or participation in clinical trial.
18. With Systolic blood pressure less than 100 mm of Hg or more than 140 mm of
Hg. Minor deviations (2-4 mm of Hg) at check-in may be acceptable at the
discretion of the Investigator.
19. With Diastolic blood pressure less than 60 mm of Hg or more than 90 mm of Hg.
Minor deviations (2-4 mm of Hg) at check-in may be acceptable at the discretion
of the Investigator.
20. Use of any insulin product in the past.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Pharmacy-controlled Randomization |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Comparative Bioavalability of test and reference product |
8 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
The secondary objective of this study is to monitor the safety and tolerability of a single
dose subcutaneous injection of RapilinTM 30 or NovoMix® 30 when administered in
healthy human adult male subjects under fasting condition |
Vital signs [blood pressure, pulse rate and temperature measurement by infrared
thermometer] and wellbeing will be assessed after dosing at 01.00, 03.00, 06.00 and
13.00 hours in each study period. In addition, at all times, subjects may report side effects
spontaneously to the monitoring staff |
|
|
Target Sample Size
|
Total Sample Size="36"
Sample Size from India="36"
Final Enrollment numbers achieved (Total)= "36"
Final Enrollment numbers achieved (India)="36" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
02/08/2023 |
| Date of Study Completion (India) |
08/11/2023 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="2"
Days="15" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
A randomized, double blinded, balanced, two treatment, two period, two sequence, cross
over, euglycemic clamp study to compare the pharmacokinetic and pharmacodynamic
activity of Insulin under fasting condition.
4.1. Primary Objective
The primary objective of this study is to
• To assess the pharmacokinetics profile of RapilinTM 30 (30% insulin aspart and
70% insulin aspart protamine suspension) injection with NovoMix® 30 (30%
insulin aspart and 70% insulin aspart protamine suspension) of Novo Nordisk,
India after single dose subcutaneous injection in healthy human adult male
subjects under fasting condition.
• To assess the pharmacodynamics profile of RapilinTM 30 (30% insulin aspart and
70% insulin aspart protamine suspension) injection with NovoMix® 30 (30%
insulin aspart and 70% insulin aspart protamine suspension) of Novo Nordisk,
India after single dose subcutaneous injection in healthy human adult male
subjects under fasting conditions using Euglycemic clamp technique by means of
Glucose Infusion Rate (GIR). The GIR time profile reflects the
pharmacodynamics time action profile of administered insulin in healthy human
adult male subjects under fasting condition.
4.2. Secondary Objective
The secondary objective of this study is to monitor the safety and tolerability of a single
dose subcutaneous injection of RapilinTM 30 or NovoMix® 30 when administered in
healthy human adult male subjects under fasting condition.
4.3. Study Rationale
This study is being conducted to compare the pharmacokinetic and pharmacodynamic
activity of RapilinTM 30 (30% insulin aspart and 70% insulin aspart protamine
suspension) injection with NovoMix® 30 (30% insulin aspart and 70% insulin aspart
protamine suspension) of Novo Nordisk, India after single dose subcutaneous injection in
healthy human adult male subjects under fasting condition Bioequivalence Criteria
Pharmacokinetic Parameter
Based on the 90% confidence intervals for the difference of means of ln-transformed
AUC0-24 and Cmax will be drawn whether the test product is bioequivalent to the
reference product under fasting condition. The acceptance range for bioequivalence is
80.00-125.00% for the 90% confidence intervals for the difference of means of lntransformed AUC0-24 and Cmax with respect to Insulin.
For Pharmacodynamic Parameters:
Based on the 95% confidence intervals for the difference of means of ln-transformed
GIR-AUC0-24 and GIRmax conclusions will be drawn whether the test product is
bioequivalent to the reference product under fasting conditions. The acceptance range
for bioequivalence is 75.00-133.00% for the 95% confidence intervals for the
difference of means of ln-transformed GIR-AUC0-24 and GIRmax with respect to
Glucose Infusion Rate.
|