CTRI/2021/09/036727 [Registered on: 22/09/2021] Trial Registered Prospectively
Last Modified On:
01/08/2022
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioavailability study between Pirfenidone ER tablet 1200 mg and PIRFENEX 200 mg tablet in healthy adult subjects at steady state
Scientific Title of Study
A randomised, open label, two-period, multiple dose cross-over bioavailability study between the test product, Pirfenidone ER tablet 1200 mg (Cipla Ltd., India) administered as one tablet twice daily with the reference product PIRFENEX (pirfenidone) 200 mg tablet (Cipla Ltd., India) administered as four tablets thrice daily in healthy adult human subjects at steady state under fed conditions.
healthy adult between 18 to 45 years of age who
have a Body Mass Index between 18.5 and 30
kg/m2 weighing not less than 45 kg
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
PIRFENEX (pirfenidone) 200
mg tablet
PIRFENEX (pirfenidone) 200
mg tablet
Dose-Oral dose of four PIRFENEX (pirfenidone) 200 mg tablet thrice daily for 5 consecutive days.
Mode of administration-To be administered orally with 240±2 mL of water under fed conditions.
Intervention
Pirfenidone ER tablet 1200 mg
Pirfenidone ER tablet 1200 mg
Dose-Oral dose of one Pirfenidone ER tablet 1200 mg twice daily for 5 consecutive days.
Mode of administration-To be administered orally with 240±2 mL of water under fed 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 have a body mass index (BMI) between 18.5 and 30 Kg per metre 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 study.
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 study.
10. Volunteers who do not have history of drug addiction or a 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 study.
11. Volunteers who are non smokers or those who are ex smokers and have less than a 10 pack-year history of smoking and have not consumed tobacco or tobacco containing products for at least 12 months prior to screening and who agree to abstain from the same until the last blood sample collection of study.
12. Volunteers agree to avoid sun exposure from check-in till post study.
13. 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.
14. Volunteers agree to refrain from driving or operating machinery till 24 hours after discharge from CPU.
15. Volunteers whose test for COVID 19 is negative (if available).
1. For female volunteers:
i. Negative beta Hcg or urine pregnancy test report showing non pregnancy.
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 to 1 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 (Evra or equivalent), vaginal ring (NuvaRing or equivalent), levonorgesterel implant (Norplant or equivalent), or injectable progesterone (Depo Provera or equivalent) 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.
ExclusionCriteria
Details
1. Volunteers who have history of known hypersensitivity to pirfenidone or related drugs.
2. Volunteers having difficulty in swallowing tablet.
3. Volunteers with history of 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) at pre-study screening and at vital signs examination before check-in.
5. Volunteers having any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract.
6. Volunteers who have clinically significant signs and symptoms or history of respiratory, cardiovascular, gastrointestinal, dermatological, neurological, psychiatric, genitourinary, endocrinological, musculoskeletal, bleeding disorder, tumor or cancer, eye, ear, nose, and throat disease.
7. 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.
8. Volunteers having Estimated Glomerular Filtration Rate (eGFR) less than 60 mL per min per 1.73 metre square calculated by MDRD (Modification of Diet in Renal Disease Study) formula.
9. 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.
10. Volunteers who have taken any drug that induces or inhibits the hepatic microsomal enzymes (including omeprazole and rifampicin) within 30 days prior to dosing.
11. Volunteers who have taken any prescription medication 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.
12. Volunteers who have depot injection or an implant of any drug within 3 months prior to dosing.
13. Volunteers having history of difficulty in donating blood.
14. Volunteers who have donated blood (1 unit or 350 mL) within 90 days prior to dosing.
15. Volunteers who have taken any investigational product or participated in any drug research study requiring blood donation within 90 days prior to dosing.
16. 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.
17. 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,ss Cmin,ss and AUC(0-t)ss for pirfenidone.
Test
Day1to4 0.00,(-96,-84, -72,-60,48,-36, -24,-12 hrs)
Day5to6: 0.00,2,4,5,6,6.5,7,8,10,12,14,16,17,18, 18.5,19,20,22,24,30,36 hrs.
Reference
Day 1 to 4: 0.00 (-96,-88,-80,-72,-64,-56,-48,-40,-32,-24,-16,-8 hrs)
Day 5 to 6: 0.00,1,2,3,3.5,4,5,6,8,9,10,11,11.5,12,13,14,16,17,18,19,19.5,20,2,22,24,30,36 hrs.
Test
Day1to4 0.00,(-96,-84, -72,-60,48,-36, -24,-12 hrs)
Day5to6: 0.00,2,4,5,6,6.5,7,8,10,12,14,16,17,18, 18.5,19,20,22,24,30,36 hrs.
Reference
Day 1 to 4: 0.00 (-96,-88,-80,-72,-64,-56,-48,-40,-32,-24,-16,-8 hrs)
Day 5 to 6: 0.00,1,2,3,3.5,4,5,6,8,9,10,11,11.5,12,13,14,16,17,18,19,19.5,20,2,22,24,30,36 hrs.
Target Sample Size
Total Sample Size="60" Sample Size from India="60" 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
This study is randomised, open label,
two-period, multiple dose cross-over bioavailability study between the test
product, Pirfenidone ER tablet 1200 mg (Cipla Ltd., India) administered as one
tablet twice daily with the reference product PIRFENEX (pirfenidone) 200 mg tablet
(Cipla Ltd., India) administered as four tablets thrice daily in healthy adult
human subjects at steady state under fed conditions. Primary objective of the
study is to compare the rate and extent of absorption of pirfenidone after
administration of multiple doses of the test product and reference product.
Secondary objective is to assess the safety and tolerability of multiple oral
doses of test and reference product in healthy adult human subjects under fed
conditions.