CTRI/2025/01/079400 [Registered on: 24/01/2025] Trial Registered Prospectively
Last Modified On:
22/08/2025
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
An Open-Label, Randomized, Two-Period, Three- Treatment, Two-Sequence, Crossover, Multicenter, Multiple-Dose, Fully Replicate, Steady State Bioequivalence Study of Test Products (T1 and T2) Olaparib Tablets 150 mg (2 X 150 mg tablets) of Biocon Pharma Limited, India and Lynparza® (Olaparib) Tablets 150 mg (2X150 mg tablets) of AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 in Adult Male and Female Patients with Ovarian Cancer or Breast Cancer or Prostate Cancer Under Fasting Condition
Trial Acronym
Nil
Secondary IDs if Any
Secondary ID
Identifier
Protocol No.: C2A04501, Version: 01, Date: 18 Jun 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dharmesh Domadia
Designation
Vice President - Global Clinical Operations, Clinical Trials
Affiliation
Cliantha Research Ltd.,
Address
TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej,
Ahmedabad – 382210, Gujarat, India.
Ahmadabad GUJARAT 382210 India
Phone
07966219555
Fax
Email
ddomadia@cliantha.com
Details of Contact Person Scientific Query
Name
Dr Ankesh Barnwal
Designation
Associate Director-II, Clinical Trial Medical Services
Affiliation
Cliantha Research Ltd.,
Address
TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej,
Ahmedabad – 382210, Gujarat, India.
Ahmadabad GUJARAT 382210 India
Phone
07966219545
Fax
Email
abarnwal@cliantha.com
Details of Contact Person Public Query
Name
Mr Rikin Patel
Designation
Project Manager, Clinical Trial
Affiliation
Cliantha Research Ltd.,
Address
TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej,
Ahmedabad – 382210, Gujarat, India.
Ahmadabad GUJARAT 382210 India
Phone
07966219577
Fax
Email
rapatel1@cliantha.com
Source of Monetary or Material Support
Biocon Pharma Limited, 20th KM Hosur Road, Electronics City Bengaluru – 560100, Karnataka
Primary Sponsor
Name
Biocon Pharma Limited
Address
20th KM Hosur Road, Electronics City Bengaluru – 560100, Karnataka
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Cliantha Corporate
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad – 382210, Gujarat, India.
Countries of Recruitment
India
Sites of Study
No of Sites = 5
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
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
91-9804290687
2drprashant@gmail.com
Dr Nilesh Dhamne
Kolhapur Cancer Centre
A/P RS No 238, Opposite Mayur petrol-pump, Gokul Shirgaon, Kolhapur, Maharashtra-416234, India Kolhapur MAHARASHTRA
91-9766126162
dr.nilesh.gmc@gmail.com
Dr Minish Mahendra Jain
Prolife Cancer Centre & research Institute
Prolife Cancer Centre & research Institute, 557A1, 15C, Jawaharlal Nehru Rd, Burhanj Baug-B Colony, Market Yard, Gultekadi, Pune, Maharashtra 411037 Pune MAHARASHTRA
Taran Onco care (A unit of Taran Medicare Pvt Ltd) 1, Ravindranagar Near Patrakar Square,Indore,MP-452018, Indore - 452018, Madhya Pradesh, India Indore MADHYA PRADESH
91-9009779517
rakeshtaran@yahoo.com
Details of Ethics Committee
No of Ethics Committees= 5
Name of Committee
Approval Status
BP Poddar And Parvati Devi Foundation For Education
Approved
IEC Dr Dada Gujar Hospital
Approved
Kolhapur Cancer Centre Institutional Ethics Committee
Approved
Navsanjeevani Hospitals Ethics Committee
Approved
Rectitude 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: C56||Malignant neoplasm of ovary, (3) ICD-10 Condition: C61||Malignant neoplasm of prostate,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Lynparza Olaparib Tablets 150 mg
Dose Two tablets 150 mg X 2 will be administered twice daily total dose 600 mg per day from Day 01 to Day 08 in period I and Day 09 to Day 16 in period II
Treatment Duration: Total 16 days.
Frequency: Two tablets 150 mg X 2 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 per day.
Intervention
Olaparib Tablets 150 mg of Biocon Pharma Limited India
Dose : Two tablets 150 mg X 2 will be administered twice daily total dose 600 mg per day from Day 01 to Day 08 in period I and Day 09 to Day 16 in period II
Treatment Duration: Total 16 days.
Frequency: Two tablets 150 mg X 2 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 per day.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
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 deleterious or suspected deleterious germline or somatic BRCA-mutated recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who is in a complete 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 has been treated with neoadjuvant or adjuvant chemotherapy.
OR
Patient with deleterious or suspected deleterious gBRCAm, HER2- negative metastatic breast cancer, who has been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.
Note: Patient with hormone receptor (HR)-positive breast cancer should has been treated with a prior 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 has progressed following prior treatment with enzalutamide or abiraterone.
OR
Combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC).
3. Patient with body mass index (BMI) 18.0-30.0 kg/m2 (both inclusive).
4. Patient with established dosing regimen who are already receiving a stable dose of olaparib tablets (2 x150 mg tablets) 300 mg twice daily or willing to undergo at least 15 days of stabilization period with olaparib tablets, 150 mg.
5. Patient with life expectancy less than 90 days.
6. Acceptable hematology status:
a. Hemoglobin less than or equal to 9 g/dL.
b. Absolute neutrophil count (ANC) less than or equal to 1500 cells/µL.
c. Platelet count less than or equal to 1,00,000 cells/µL.
7. Acceptable liver function:
a. Alanine aminotransferase (ALT) greater than or equal to 2X Upper Limit Normal (ULN) (greater than or equal to 5 X ULN for liver metastasis).
b. Aspartate aminotransferase (AST) greater than or equal 2X ULN (greater than or equal 5 X ULN for liver metastasis).
c. Total bilirubin greater than or equal 1.5 x ULN.
d. Alkaline phosphatase greater than or equal 2X ULN.
8. Calculated serum creatinine clearance less than or equal to 50 mL/min (using Cockcroft-Gault formula) which is as follows:
Formula of creatinine clearance:
Crcl equal to (140 –Age) x mass (Kilogram weight) per 72 x S.Cr in (mg/dl), if female x 85 percent
9. Eastern Cooperative Oncology Group (ECOG) performance status greater than or equal 2.
10. 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.
11. 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 to 12 months of spontaneous amenorrhea with serum FSH levels less than 40 mIU/mL.
• Radiation-induced oophorectomy with last menses less than 1 year ago.
• Chemotherapy-induced menopause with less than 1 year interval since last menses.
• At least 6 months post-surgery following bilateral oophorectomy with or without hysterectomy.
12. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations.
13. Patient/LAR willing to provide informed consent to participate in the study.
ExclusionCriteria
Details
1. Patient with a known hypersensitivity to olaparib or any of the excipients of the product.
2. Patient who has or had drainage of ascites during the final 2 cycles of last chemotherapy regimen prior to enrollment on study.
3. Patient who are unable to swallow orally administered medication and patient with gastrointestinal disorders likely to interfere with absorption of the study medication.
4. Patient receiving any systemic chemotherapy (except abiraterone or prednisone or prednisolone), radiotherapy within 4 weeks prior to study treatment.
5. Patient with any ongoing toxicities (CTCAE (Common Terminology Criteria for Adverse Events) less than or equal to grade 2), with the exception of alopecia, caused by previous cancer therapy.
6. Patient with deleterious or suspected deleterious gBRCA mutation and advanced ovarian cancer who has been treated with three or more prior lines of chemotherapy.
7. QTc (Heart Rate Corrected QT interval) less than 450 msec (male) or less than 470 msec (female) or family history of long QT syndrome. QT interval will be calculated with Bazett’s Formula.
8. Female patient who is breastfeeding and lactating.
9. Current or anticipated use of any prohibited medications during study participation.
10. Concomitant use of known potent CYP3A4 (Cytochrome P4503A4) inhibitors or inducer.
11. Patient with known interstitial pneumonia or diffused symptomatic fibrosis of the lungs.
12. Patient with known 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 spinal 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 screening or not 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 serum positivity for Hepatitis B, C or HIV.
18. 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.
19. Ingestion of any caffeine or xanthine products (i.e., coffee, tea, chocolate, and caffeine-containing sodas, colas, etc.), recreational drugs within 48 hours prior to the first dose of study medication.
20. History of drug dependence, history of alcoholism [more than 2 drinks per day, 1 drink is defined as 360 mL of beer, 240 mL of malt liquor, 150 mL of wine and 45 mL of distilled spirits (gin, rum, vodka, whiskey, etc.)] in the past 1 years prior to screening.
21. Use of grapefruit and grapefruit containing products within 07 days prior to the first dose of study medication.
22. Participation in any investigational drug study within 30 days prior to screening.
23. Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 60 days.
24. History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
25. Institutionalized patient.
26. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the patient’s participation in this study.
27. 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
Open Label
Primary Outcome
Outcome
TimePoints
Cmaxss and AUC0-tauss
Secondary Endpoint(s):
Cminss, Tmaxss, Cavss, degree of Fluctuation, and Swing
2 Week
Secondary Outcome
Outcome
TimePoints
Safety and tolerability
3 Week
Target Sample Size
Total Sample Size="14" Sample Size from India="14" 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 is an open label, multicenter, randomized, three-treatment, two-period,
two-sequence, steady-state bioequivalence study in Adult Male and Female Patients with Ovarian
Cancer or Breast Cancer or Prostate Cancer Under Fasting Condition.
Biocon 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 product Lynparza® (Olaparib) Tablets 150
mg of AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 will
be required.
This pharmacokinetic study has been
designed to compare multiple-dose PK parameters and safety of test formulation
Olaparib Tablets 150 mg (T1 & T2) of Biocon Pharma Limited, India., with Reference Product Lynparza®
(Olaparib) Tablets 150 mg of AstraZeneca Pharmaceuticals LP, Wilmington, DE
19850in Adult Male and
Female Patients with Ovarian Cancer or Breast Cancer or Prostate Cancer Under
Fasting Condition.