CTRI/2023/10/058337 [Registered on: 05/10/2023] Trial Registered Prospectively
Last Modified On:
03/10/2024
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
Bioequivalence study in Adult Male and Female Patients with Ovarian Cancer or Breast Cancer or Prostate Cancer Under Fasting Condition.
Scientific Title of Study
A Double Blind, Multicenter, Randomized, Three-Treatment, Three-Period, Six-Sequence, Steady-State Bioequivalence Study of Test Product (A) Olaparib Tablets 150 mg (2 into 150 mg tablets) of Natco Pharma Limited, India with Reference Product (B1) Lynparza tablets (Olaparib) 150 mg (2 into 150 mg tablets) of AstraZeneca do Brasil Ltda and Reference Product (B2) PrLYNPARZA® Olaparib Tablets 150 mg (2 into 150 mg tablets) of AstraZeneca Canada Inc. in Adult Male and Female Patients with Ovarian Cancer or Breast Cancer or Prostate Cancer Under Fasting Condition.
Clinical Research Department, Second Floor, "B" Tower, Sundervan Complex, Beside IOCL Petrol Pump, Near Gorwa ITI, Gorwa, Vadodara-390016, Gujarat, India. Vadodara GUJARAT
8780466776
amhctbaroda@gmail.com
Dr Shailesh Bondarde
Apex Wellness Hospital
Survey no.799, Plot no.187, Behind Prakash Petrol Pump, Govind Nagar, Nashik, Maharashtra, India Nashik MAHARASHTRA
9822012427
shaileshbondarde1971@gmail.com
Dr Prashant Pandey
B.P. Poddar Hospital & Medical Research Ltd.
Clinical Research Department, Sixth Floor, 71/1, Humayun Kabir Sarani, Block G, New Alipore, Kolkata-700053, West Bengal, India. Kolkata WEST BENGAL
9804290687
2drprashant@gmail.com
Dr Minish Jain
CIMETs Inamdar Multispeciality Hospital
Oncology Department, Clinical Research Division, Extension Building (Sr. No.-15), Pune Hospital Building, S. No. 15, behind KPCT mall, Fatima Nagar, Wanowrie, Pune-411040, Maharashtra, India. Pune MAHARASHTRA
9823133390
minishjain009@gmail.com
Dr K Velavan
Erode Cancer Centre
Department of Radiation Oncology, Clinical Research Division, Ground Floor, SH 1/393, Velavan Nagar, Perundurai Road, Thindal, Erode-638012, Tamil Nadu, India. Erode TAMIL NADU
9842334222
kvels@rediffmail.com
Dr Akash Patel
HCC (Happiness Care & Cure) Multispeciality Hospital
Department of Oncology, Second Floor, 33-25-33, CH Venkata, Gopala Krishnaiah Street, Suryarao pet, Guntur, Vijayawada-520002, Andhra Pradesh, India. Guntur ANDHRA PRADESH
9801992974
vasu.onco3@gmail.com
Dr Rajnish Nagarkar
HCG Manavata Cancer Center
Surgical Oncology Department, First Floor, Near Mylan Circle, Behind Shivang Auto, Mumbai Naka, Nashik-422002, Maharashtra, India. Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Santhosh Vandanasetti
Kailash Cancer Hospital and Research Center
Clinical Research Department, Muni Seva Ashram, Goraj, Ta. Waghodia, Vadodara-391760, Gujarat, India. Vadodara GUJARAT
9427423693
santu.vandanasetti@gmail.com
Dr Nilesh Ashok Dhamne
Kolhapur Cancer Centre Pvt Ltd.
Clinical Research Department, Third Floor, R. S. No.: 238, Opposite Mayur Petrol Pump, Gokul Shirgaon, Kolhapur - 416234,, Maharashtra, India. Kolhapur MAHARASHTRA
7738245698
dr.nilesh.gmc@gmail.com
Dr Saju S V
Meenakshi Mission Hospital & Research Centre
Department of Radiation Oncology, Clinical Research Division, Ground Floor, Lake Area, Melur Road, Madurai-625107, Tamil Nadu, India. Madurai TAMIL NADU
9380417299
drsajusv@gmail.com
Dr Anilkumar MR
Oncoville Cancer Hospital & Research Center
Department of Radiation Oncology, Clinical Trial Division, Third Floor, No. 4, 80 Ft. Road, 7th Block, Nagarbhavi 2nd Stage, Bengaluru-560072, Karnataka, India. Bangalore KARNATAKA
9739808502
dranilonco@gmail.com
Dr K N Lokesh
Radhakrishna Multispeciality Hospital
Oncology Department, Clinical Research Division, Fourth Floor, 3-4 Sunrise Towers, JP Road, Opposite Canara Bank, 1st Phase Girinagar, Bengaluru -560085, Karnataka , India. Bangalore KARNATAKA
8971609070
drlokeshkidwai.research@gmail.com
Dr Ghanashyam Biswas
Sparsh Hospital & Critical Care Private Limited
Department of Medical Oncology, Clinical Research Division, Ground Floor, A/407, Back Side of Kalyan Jewelers, Saheed Nagar, Bhubaneshwar-751007, Odisha, India. Khordha ORISSA
9937500878
drgbiswas@gmail.com
Dr K Srinivasan
Srinivasan Rajalakshmi Memorial Hospital
11 77, 6th street, Voltas colony, Nanganallur, Chennai - 600061, Tamil Nadu, India.
Chennai TAMIL NADU
9444896010
drseeni23@gmail.com
Dr Divyeshkumar Rana
SSG Hospital
Clinical Study Room, 2nd Floor, Department of Radiation Oncology, SSG Hospital, Jail road, Indira Avenue, Vadodara, Gujarat-390001, India
Vadodara GUJARAT
9429338738
divyeshbmc@gmail.com
Dr Rajender Singh Arora
Sujan Surgical & Cancer Hospital and Amravati Cancer Foundation
Clinical Research Department, 1st Floor, Clinical Trial Room, 52/B, Main Road, Shankar Nagar, Amravati-444606, Maharashtra, India. Amravati MAHARASHTRA
9823097573
dr_rsarora@rediffmail.com
Dr Ankit Patel
Sunshine Global Hospital (A unit of Baroda Medicare Pvt Ltd)
Clinical Research Department, First Floor, Beside Big Bazaar, Gaurav Path, Dumas - Piplod Road, Surat-395007, Gujarat, India. Surat GUJARAT
9825404202
drankitoncologist@gmail.com
Dr Mukul Gharote
Surya Multi-Speciality Hospital
Clinical Research Department, Surya Arcade, 2nd floor, Opposite Nimani Bus Stand, Panchvati, Nashik-422003, Maharashtra, India. Nashik MAHARASHTRA
8758052774
mukul.gharote@gmail.com
Dr Bhavana Parikh
Unity Hospital
Oncology Department, Ground Floor, Shripal Nagar Society, 51, New C. G. Road, Opposite Pebble Bay Flats, Ahmedabad-Patan Highway Road, Janta Nagar, Chandkheda, Ahmedabad - 382424, Gujarat, India Ahmadabad GUJARAT
Institutional Ethics Committee BP Poddar And Parvati Devi Foundation For Education
Approved
Institutional Ethics Committee Erode Cancer Centre
Approved
Institutional Ethics Committee for Human Research Medical College
Approved
Institutional Ethics Committee of OCH and RC
Approved
Institutional Ethics Committee Sparsh Hospital
Approved
Institutional Ethics Committee Sunshine Global Hospital
Approved
Kolhapur Cancer Centre Institutional Ethics Committee
Approved
Leelavati Ethics Committee
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
Parth Hospital Ethics Committee
Approved
Shakti Hospital Ethics Committee
Approved
Universal Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C50||Malignant neoplasm of breast, (2) ICD-10 Condition: C61||Malignant neoplasm of prostate, (3) ICD-10 Condition: C56||Malignant neoplasm of ovary,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
(Reference Product-B1) Lynparza tablets (Olaparib) 150 mg of AstraZeneca do Brasil Ltda
Dose: Two tablets (150 mg X 2 equals to 300mg) will be administered twice daily (total dose: 600 mg/day) from Day 01 to Day 06 in period I, Day 07 to Day 12 in period II and Day 13 to Day18 in period III.) Treatment Duration: Total 18 days. Frequency: Two tablets (150 mg X 2 equals to 300mg) will be administered in the morning and evening, at an interval of around 12 hours between the doses, i.e., twice daily (total dose: 600 mg/day).
Comparator Agent
(Reference Product-B2) PrLYNPARZA® Olaparib Tablets 150 mg of AstraZeneca Canada Inc. 1004, Middlegate Road, Suite 5000, Mississauga, Ontario L4Y 1M4
Dose: Two tablets (150 mg X 2 equals to 300mg) will be administered twice daily (total dose: 600 mg/day) from Day 01 to Day 06 in period I, Day 07 to Day 12 in period II and Day 13 to Day18 in period III.) Treatment Duration: Total 18 days. Frequency: Two tablets (150 mg X 2 equals to 300mg) will be administered in the morning and evening, at an interval of around 12 hours between the doses, i.e., twice daily (total dose: 600 mg/day).
Intervention
(Test Product-A) Olaparib Tablets 150 mg of Natco Pharma Limited., India
Dose: Two tablets (150 mg X 2 equals to 300mg) will be administered twice daily (total dose: 600 mg/day) from Day 01 to Day 06 in period I, Day 07 to Day 12 in period II and Day 13 to Day18 in period III.)
Treatment Duration: Total 18 days.
Frequency: Two tablets (150 mg X 2 equals to 300mg) will be administered in the morning and evening, at an interval of around 12 hours between the doses, i.e., twice daily (total dose: 600 mg/day).
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Inclusion Criteria: Patient will be eligible for inclusion in this study only if all of the following criteria apply:
1. Male or non-pregnant, non-lactating female between 18-65 years of age (both inclusive).
2. Patient with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who is in a complete or partial response to first-line platinum-based chemotherapy. OR Patient with platinum-sensitive relapsed (PSR) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy. OR Patient with deleterious or suspected deleterious gBRCAm human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. OR Patient with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have progressed on endocrine therapy or be considered inappropriate for endocrine therapy. OR Patient with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. OR Combination of abiraterone and prednisone or prednisolone for treatment of metastatic castration-resistant prostate cancer.
3. Patient with body mass index (BMI) 18.5 to 30.0 kg/m2 (both inclusive).
4. Patient with established dosing regimen who are already receiving a stable dose of olaparib tablets (2 into 150 mg tablets) 300 mg twice daily or willing to undergo at least 15 days of stabilization period with olaparib tablets, 150 mg.
NOTE: For the patients who will enter into the stabilization period, the criteria will be evaluated during screening part II.
5. Patient having body weight ≥ 45 Kg.
6. Patient with life expectancy > 90 days.
7. Acceptable hematology status:
a. Hemoglobin ≥ 9 g/dL.
b. Absolute neutrophil count (ANC) ≥ 1500 cells/µL.
c. Platelet count ≥ 1,00,000 cells/µL.
8. Acceptable liver function:
a. Alanine aminotransferase (ALT) ≤ 2X upper limit of normal (ULN).
b. Aspartate aminotransferase (AST) ≤ 2X ULN.
c. Total bilirubin ≤ 1.5 x Upper Limit Normal (ULN).
d. Alkaline phosphatase ≤ 2X ULN.
9. Calculated serum creatinine clearance ≥ 50 mL/min (using Cockroft-Gault formula) which is as follows:
Formula of creatinine clearance: Crcl equals to (140-Age) x mass (Kilogram weight) / 72 x S.Cr in (mg/dl) if ‘female’ x 85 percentage.
10. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
11. Non-smokers and non-tobacco users (i.e., having no past history of smoking and tobacco consuming for at least one year prior to study).
12. Male patient if sexually active with a female of child bearing potential must agree to use barrier method of contraception throughout the study period and for at least 6 months after last dose of study drug.
13. Female with postmenopausal status or female of child bearing potential with negative pregnancy test must agree to practice an acceptable method of contraception throughout the study period and for at least 6 months after last dose of study drug. Postmenopausal is defined by any one of the following:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments.
• 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL.
• Radiation-induced oophorectomy with last menses > 1 year ago.
• Chemotherapy-induced menopause with > 1 year interval since last menses.
• At least 6 months post-surgery following bilateral oophorectomy with or without hysterectomy.
14. Patient who had taken COVID 19 vaccine, must recovered from vaccine related adverse events before being screened for the study.
15. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations.
16. Patient/LAR willing to provide informed consent to participate in the study.
ExclusionCriteria
Details
Exclusion Criteria: Patient will not be eligible for inclusion in this study if any of the following criteria apply:
1. Patient with a known hypersensitivity to olaparib or any of the excipients of the product.
2. Patient having signs and symptoms suggestive of COVID-19 (such as fever, dry cough, difficulty in breathing and fatigue).
3. Patient who has or had drainage of ascites during the final 2 cycles of last chemotherapy regimen prior to enrollment on study.
4. Patient who are unable to swallow orally administered medication and patient with gastrointestinal disorders likely to interfere with absorption of the study medication.
5. Patient receiving any systemic chemotherapy, radiotherapy within 4 weeks prior to study treatment.
6. Current or anticipated use of any prohibited medications during study participation.
7. Female patient who is breastfeeding and lactating.
8. Concomitant use of known potent CYP3A4 (Cytochrome P4503A4) inhibitors or inducer.
9. Patient with any ongoing toxicities (CTCAE (Common Terminology Criteria for Adverse Events) ≥ grade 2), with the exception of alopecia, caused by previous cancer therapy.
10. QTc (Heart Rate Corrected QT interval) > 450 msec (male) or > 470 msec (female) or family history of long QT syndrome. QT interval will be calculated with Bazett’s Formula.
11. Patient with interstitial pneumonia or diffused symptomatic fibrosis of the lungs.
12. Patient with myelodysplastic syndrome/acute myeloid leukemia.
13. Patient with history/ risk of venous thromboembolic events.
14. Patient with symptomatic uncontrolled brain metastases. Patient can receive stable dose of steroids before and during study as long as these were started at least 4 weeks prior to treatment. Patient with cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
15. Major surgery within 2 months of study starting and patient must have recovered from any undesirable or harmful effects of any major surgery.
16. History of other malignancies in the last 5 years (Potential patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible).
17. Patient with known serum positivity for Hepatitis B, C or HIV.
18. Ingestion of any caffeine or xanthine products (i.e., coffee, tea, chocolate, and caffeine-containing sodas, colas, etc.), recreational drugs, dietary items that have effect on P450 enzymes (e.g., pomegranate, star fruit, seville oranges) & PGP (P-Glycoprotein) efflux pump (e.g., St. John’s wort) within 48 hours prior to the first dose of study medication.
19. Use of grapefruit and grapefruit containing products within 07 days prior to the first dose of study medication.
20. Patient who has received an investigational drug or participation in drug research study within 06 months prior to the first dose of study medication.
21. Donation of blood (excluding volume drawn at screening for this study) within 06 months prior to the first dose of study medication.
22. History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
23. Any significant disease or condition which might compromise the haemopoeitic, gastrointestinal (e.g., pancreatitis), renal, hepatic, cardiovascular, respiratory, central nervous system, diabetes, psychosis, or any other body system.
24. Institutionalized patient.
25. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the patient’s participation in this study.
26. Any other condition that, in the investigator’s judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
CmaxSS, Cminss and AUC
3 week
Secondary Outcome
Outcome
TimePoints
Cminss, Tmaxss, Cavss, swing
3 week
Target Sample Size
Total Sample Size="42" Sample Size from India="42" Final Enrollment numbers achieved (Total)= "42" Final Enrollment numbers achieved (India)="42"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a double blind, multicenter, randomized, three-treatment, three-period,
six-sequence, steady-state bioequivalence study in adult male and female
patients with ovarian cancer or breast cancer or prostate cancer under fasting
condition.
Natco Pharma Limited, India is
seeking approval for the generic drug application of Olaparib Tablets 150 mg,
for which demonstration of bioequivalence to the reference listed products
Lynparza tablets (Olaparib) 150 mg (2*150 mg tablets) of AstraZeneca do Brasil
Ltda, and PrLYNPARZA® Olaparib Tablets 150 mg (2*150 mg tablets) of
AstraZeneca Canada Inc., will be required.
This pharmacokinetic study has been designed to
compare multiple-dose PK parameters and safety of test formulation Olaparib
Tablets 150 mg of Natco Pharma Limited, India, with Reference Product (B1) Lynparza tablets (Olaparib) 150 mg (2*150
mg tablets) of AstraZeneca do Brasil Ltda, and Reference Product (B2) PrLYNPARZA® Olaparib Tablets 150 mg (2*150 mg tablets) of
AstraZeneca Canada Inc. in adult male and female patients with ovarian
cancer or breast cancer or prostate cancer under fasting condition.