CTRI/2022/05/042589 [Registered on: 17/05/2022] Trial Registered Prospectively
Last Modified On:
25/07/2022
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
Bioequivalence study between Nirmatrelvir 300mg (2 x 150 mg) and Ritonavir 100 mg tablet and PAXLOVID Tablet in healthy adult human subjects
Scientific Title of Study
A randomised, open label, two-treatment, two-period, cross-over, single dose oral
bioequivalence study between test product, Nirmatrelvir 300mg (2 x 150 mg)
tablets and Ritonavir 100 mg tablet (Cipla Ltd., India) and the reference product,
PAXLOVID (Nirmatrelvir 300mg [2 x 150 mg] tablets and Ritonavir 100 mg
tablet) (Distributed By: Pfizer labs, Division of Pfizer Inc. New York, NY10017)
in healthy adult human subjects under fasting conditions.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
22-01-014 Version No. 07 Date 21 April 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Shrikant Madrewar
Designation
Principal Investigator
Affiliation
Sitec Labs Limited
Address
Sitec Labs Ltd.
Plot No. Gen 40 TTC Industrial Area MIDC Near Nelco Bus Stop Behind Millennium Business Park Mahape
Navi Mumbai 400710 India
Thane MAHARASHTRA 400710 India
Phone
8668622861
Fax
Email
shrikant.madrewar@siteclabs.com
Details of Contact Person Scientific Query
Name
Dr Sandeep Chaubey
Designation
Manager
Affiliation
Cipla Limited
Address
Cipla Limited
R & D centre North Block
LBS Road Vikhroli West
Mumbai 400083 India
Mumbai (Suburban) MAHARASHTRA 400083 India
Phone
9823066463
Fax
Email
Sandeep.Chaubey@Cipla.com
Details of Contact Person Public Query
Name
Dr Sandeep Chaubey
Designation
Manager
Affiliation
Cipla Limited
Address
Cipla Limited
R & D centre North Block
LBS Road Vikhroli West
Mumbai 400083 India
Mumbai (Suburban) MAHARASHTRA 400083 India
Phone
9823066463
Fax
Email
Sandeep.Chaubey@Cipla.com
Source of Monetary or Material Support
Cipla House, Peninsula Business Park, Ganpatrao Kadam Marg, Lower Parel, Mumbai - 400013, Maharashtra, India
Primary Sponsor
Name
Cipla Limited
Address
Cipla House, Peninsula Business Park, Ganpatrao Kadam Marg, Lower Parel, Mumbai - 400013, Maharashtra, India
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 1
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Shrikant Madrewar
Sitec Labs Limited
Sitec Labs Ltd.
Plot No. Gen-40, TTC Industrial Area, MIDC, Near Nelco Bus Stop, Behind Millennium Business Park, Mahape,
Navi Mumbai- 400710, India. Thane MAHARASHTRA
8668622861
shrikant.madrewar@siteclabs.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Suraksha-Ethics committee
Approved
Regulatory Clearance Status from DCGI
Status
No Objection Certificate
Health Condition / Problems Studied
Health Type
Condition
Healthy Human Volunteers
Healthy willing adult human volunteers having an age between 18 to 45 years (both inclusive), having body mass index (BMI) between 18.5 and 30 kg/m2, weighing not less than 45 kg
Intervention / Comparator Agent
Type
Name
Details
Intervention
Nirmatrelvir and Ritonavir 300/100 mg (Cipla Ltd., India).
Nirmatrelvir and Ritonavir 300/100 mg (Cipla Ltd., India).
Dose - Single oral dose of two Nirmatrelvir 150 mg tablets and one Ritonavir 100 mg
tablet.
Mode of administration - To be administered orally with 240±2 mL of water while the subject is seated upright under fasting conditions.
Comparator Agent
PAXLOVID (Nirmatrelvir 300mg [2 x 150 mg] Tablets and Ritonavir 100 mg)
Tablet (Distributed By: Pfizer labs, Division of Pfizer Inc. New York, NY10017)
PAXLOVID (Nirmatrelvir 300mg [2 x 150 mg] Tablets and Ritonavir 100 mg)
Tablet (Distributed By: Pfizer labs, Division of Pfizer Inc. New York, NY10017)
Dose - Single oral dose of two Nirmatrelvir 150 mg tablets and one Ritonavir 100 mg
tablet.
Mode of administration - To be administered orally with 240 ± 2 mL of water while the subject is seated upright under fasting conditions.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
45.00 Year(s)
Gender
Both
Details
1. Volunteers who give consent by signing the informed consent form after understanding the study related information about the nature, risk, and scope of the clinical study as well as the expected
adverse effects of the drug.
2. Volunteers who are healthy adult between 18 to 45 years of age both inclusive of Asian Indian origin.
3. Volunteers who have a Body Mass Index between 18.5 and 30 kg per meter square, weighing not less than 45 kg.
4. Volunteers who have no evidence of any significant diseases or clinically significant abnormal findings during the pre-study screening, medical and medication histories, vital signs examination,
physical examination, 12-lead electrocardiogram ECG, and chest X-ray postero-anterior view recorded in last 180 days.
5. Volunteers, whose urine alcohol test and urine test for drugs of abuse are negative and whose Rapid Plasma Reagin RPR, Hepatitis B Surface Antigen HBsAg, Hepatitis C Anti HCV and
antibodies to human immuno-deficiency Virus HIV I and II are negative or non-reactive.
6. Volunteers whose pre-study screening laboratory tests are within normal limit or clinically not significant.
7. Volunteers who have agreed to follow the appropriate distancing, all the necessary safety precautions like wearing mask, using hand sanitizer etc. during the study.
8. Volunteers who agree to abstain from consuming grapefruit or its products for at least 72 hours prior to dosing and until the last blood sample collection of each study period.
9. Volunteers who agree to abstain from consuming citrus fruits or their products and xanthine containing products chocolate, tea, coffee or cola drink, for at least 24 hours prior to dosing and
until the last blood sample collection of each study period.
10. Volunteers who do not have history of drug addiction or habit of heavy drinking which is defined as regular intake of more than 2 units of alcohol per day for males and 1 unit for females, 1 unit is equal to 150 mL of wine or 360 mL of beer or 45 mL of 40 percent alcohol and those who agree to abstain from consuming alcohol or alcoholic products for at least 48 hours prior to dosing and until
the last blood sample collection of each study period.
11. Volunteers who are non-smokers or those who are ex-smokers with less than 10 pack-year history Volunteers must agree to be available for the entire study and have the ability to understand and
communicate effectively with the investigators and study personnel.
12. Volunteers must agree to be available for the entire study and have the ability to understand and communicate effectively with the investigators and study personnel.
13. Volunteers who agree to avoid driving vehicles and operating machines 24 hours after discharge from clinical facility.
14. Volunteers whose test for COVID-19 is negative.
15. For female volunteers:
i. non pregnant as per pregnancy test.
ii. who is currently not pregnant, breast feeding, or attempting to be pregnant from the screening visit and throughout the duration of the study, and is of Non-childbearing, defined as more than or equal to1 year post-menopausal or Surgically sterile, tubal ligation, oophorectomy or hysterectomy or Diagnosed as infertile and not undergoing treatment to reverse infertility or is of
Child-bearing potential, willing to commit to using a consistent and acceptable method of birth control as defined below for the duration of the study: Systemic contraception used from the time of screening including birth control pills, transdermal patch, vaginal ring, levonorgesterel implant Norplant or
equivalent), or injectable progesterone or Double barrier methods condoms, cervical cap, diaphragm, and vaginal contraceptive film with spermicide or Intrauterine device IUD with a low failure rate less than 1 percent per year
or is of
Child-bearing potential and not sexually active, willing to commit to using a consistent and acceptable method of birth control as defined above for the duration of the study, in the event the subject become sexually active. prior to screening and who agree to abstain from the same until the last blood sample collection of the last treatment period.
ExclusionCriteria
Details
1. Volunteers who have history of known hypersensitivity to nirmatrelvir and ritonavir or related class of drug.
2. Volunteers having difficulty in swallowing tablet.
3. Volunteers with history of a known food allergy.
4. Volunteers who have vital signs abnormalities , systolic blood pressure less than 100 or greater than 140 mm of Hg or diastolic blood pressure less than 60 or greater than 90 mm of Hg or pulse
rate less than 50 beats per minute or more than 100 beats per minute during pre-study screening and vital signs examination before check-in.
5. Volunteers with history of acute pancreatitis.
6. Volunteers with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or severe lactase deficiency.
7. Volunteers having any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract.
8. Volunteers who have recent history of dehydration from diarrhoea, vomiting or any other reason within a period of 24 hours prior to the study check-in.
9. Volunteers who have clinically significant signs and symptoms or history of respiratory, cardiovascular, gastrointestinal, dermatological, renal, hepatic, neurological, psychiatric, genitourinary, endocrinological, musculoskeletal, bleeding disorder, tumor or cancer, eye, ear, nose and throat disease.
10. Volunteers who have suffered any clinically significant illness in the 2 weeks prior to dosing or who have been hospitalized within 3 months preceding the start of the study.
11. Volunteers who have suffering from active skin infection.
12. Volunteers who have taken any drug that induces or inhibits the hepatic microsomal enzymes within 30 days prior to dosing.
13. Volunteers who have taken any prescription medication, including apalutamide, anticonvulsants, antifungal, rifampin, St. Johns Wort or over-the-counter products available, including vitamins
and products from natural origin such as ayurvedic, unani, siddha and homeopathic medicines and topical medication meant for systemic absorption, within the 7 days prior to dosing.
14. Volunteers who have depot injection or an implant of any drug within 3 months prior to dosing.
15. Volunteers who have a history of difficulty in donating blood.
16. Volunteers who have donated blood,1 unit or 350 mL within 3 months prior to dosing.
17. Volunteers having Estimated Glomerular Filtration Rate less than 60mL per min per 1.73metre square calculated by Modification of Diet in Renal Disease Study formula.
18. Volunteers who have taken any investigational product or participated in any drug research study requiring blood donation within 90 days prior to dosing.
19. Volunteers who have unsuitable veins for repeated venipuncture, evidence of skin lesions on forearm or signs of venipuncture on the forearm suggestive of recent blood donation or
participation in a study.
20. Female volunteers who have clinically significant signs and symptoms or history of gynaecological disease.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Cmax, AUC0-t and AUC0-infinity
Sampling time points are 0.00, 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.25, 2.50, 2.75, 3.00, 3.25, 3.50, 3.75,
4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 and 36.00 hours post-dose.
Secondary Outcome
Outcome
TimePoints
Tmax, T1/2, Residual area (%): Extrapolated area [(AUC0-∞ - AUC0-t)/ AUC0-∞] x 100 and Kel
Sampling time points are 0.00, 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.25, 2.50, 2.75, 3.00, 3.25, 3.50, 3.75,
4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 and 36.00 hours post-dose.
Target Sample Size
Total Sample Size="48" Sample Size from India="48" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
A randomised, open label, two-treatment, two-period, cross-over, single dose oral bioequivalence study between test product, Nirmatrelvir 300mg (2 x 150 mg) tablets and Ritonavir 100 mg tablet (Cipla Ltd., India) and the reference product,
PAXLOVID (Nirmatrelvir 300mg [2 x 150 mg] tablets and Ritonavir 100 mg tablet) (Distributed By: Pfiznr labs, Division of Pfizer Inc. New York, NYl0017) in healthy adult human subjects under fasting conditions.
To compare the rate and extent of absorption of the test product and reference product. Secondary objective is to assess the safety and tolerability of single dose of Nirmatrelvir and Ritonavir 300/100 mg Tablet in healthy adult human subjects.
Bioequivalence will be concluded if the confidence interval so constructed fall within the range of 80–125% for (ln-transformed) Cmax and AUC0-t for nirmatrelvir.