CTRI/2024/09/073986 [Registered on: 17/09/2024] Trial Registered Prospectively
Last Modified On:
28/02/2025
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 Fed Condition
Scientific Title of Study
A Randomized, Open-Label, Multicenter, Two- Treatment, Two-Period, Two-Sequence, Crossover, Steady-State Bioequivalence Study of Test Product Olaparib Tablets 150 mg (2 x150 mg tablets) of Natco Pharma Limited, India with Reference Product Lynparza (Olaparib) Tablets 150 mg (2 x 150 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 Fed Condition
Memco Cross Road, Naroda Road, Ahmedabad-382345, Gujarat Ahmadabad GUJARAT
99099142228
drkalpeshprajapati.research@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 Kartikeya Jain
Bankers Superspeciality Hospital
Division of Bankers Cardiology, GIDC Road, Opp-Mahalakshmi Party Plot, Tulsidham, GIDC Industrial Area, Manjalpur, Vadodara, Gujarat-390011
Vadodara GUJARAT
9427432642
divahogclinic@gmail.com
Dr Tanmoy Kumar Mandal
Binayak Multi-Speciality Hospital,
Binayak Multi-Speciality Hospital, Medical Oncology Department, Ground Floor, Binayak Enclave, 59, Kalicharan Ghosh Road, Bidhan Park, Sadhan Pally, PS:, Baranagar, Kolkata-700050, West Bengal, India. Kolkata WEST BENGAL
9051238499
tanmoy.nrs@gmail.com
Dr Minish Mahendra Jain
CIMETs Inamdar Multispeciality Hospital
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
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 Arun Seshachalam
GVN Riverside Multispeciality Hospital
Trichy-Chennai National Highway, Thimmarayasamudram, T.V. Kovli, ,Tiruchirappalli ,Trichy 620005, Tamil Nadu, India Tiruchirappalli TAMIL NADU
9786220191
gvnriversidecrc@gmail.com
Dr Patel Akash Dineshbhai
HCC Happiness Care and Cure Multispeciality Hospital LLP
BP Poddar And Parvati Devi Foundation For Education
Approved
Erode Cancer Centre Private Ltd
Approved
Ethics Committee of Ishwar Institute of HealthCare
Approved
ETHICS COMMITTEE, S.P.MEDICAL COLLEGE
Approved
ETHICS COMMITTEE, SANJEEVANI CANCER HOSPITAL
Approved
IEC Anand Surgical Hospital Pvt Ltd
Approved
IEC LIFELINE DIAGNOSTIC CENTER
Approved
IEC-KCHRC
Approved
Inamdar Multispeciality Hospital CIMETs Hospital
Approved
Institutional Ethics Commitee Maccare Hospital
Approved
Institutional Ethics Committee
Approved
INSTITUTIONAL ETHICS COMMITTEE - HCG CURIE CCC
Approved
Institutional Ethics Committee Aram Hospital
Approved
Institutional Ethics Committee HCG Cancer Centre
Approved
Institutional Ethics Committee Sunshine Global Hospital
Approved
KCC Institutional Ethics Committee
Approved
Omega Ethical Committee
Approved
Parth Hospital Ethics Committee
Approved
Rectitude Ethics Committee
Approved
Rectitude Ethics Committee
Approved
Regency Hospital Ethics Committee
Approved
Treat Me Hospital Institutional 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 Tablets 150 mg
Dose Two tablets 150 mg X 2 will be administered twice daily total dose 600 mg/day from Day 01 to Day 06 in period I and Day 07 to Day 12 in period II
Treatment Duration Total 12 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/day
Intervention
Olaparib Tablets 150 mg
Dose Two tablets 150 mg X 2 will be administered twice daily total dose 600 mg/day from Day 01 to Day 06 in period I and Day 07 to Day 12 in period II
Treatment Duration Total 12 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/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.
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 are in a complete or partial response to platinum-based chemotherapy and is in maintenance treatment.
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
Note: Patients with hormone receptor (HR)-positive breast cancer should have 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 have 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 to 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.
NOTE: For the patients who will enter into the stabilization period, the criteria will be evaluated during screening part II
5. Patient with life expectancy less than 90 days.
6. Acceptable hematology status:
a. Hemoglobin ≥ 9 g/dL.
b. Absolute neutrophil count (ANC) ≥ 1500 cells/µL.
c. Platelet count ≥ 1,00,000 cells/µL.
7. 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.
8. Calculated serum creatinine clearance ≥ 50 mL/min using Cockcroft-Gault formula
9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 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, radiotherapy within 4 weeks prior to study treatment.
5. Patient with any ongoing toxicities CTCAE ≥ grade 2 with the exception of alopecia, caused by previous cancer therapy.
6. 6. QTc Heart Rate Corrected QT interval less than 450 msec male or less than470 msec female or family history of long QT syndrome. QT interval will be calculated with Bazetts Formula.
7. Female patient who is breastfeeding and lactating.
8. Current or anticipated use of any prohibited medications during study participation.
9. Concomitant use of known potent CYP3A4 Cytochrome P4503A4 inhibitors or inducer.
10. Patient with interstitial pneumonia or diffused symptomatic fibrosis of the lungs.
11. Patient with myelodysplastic syndrome/acute myeloid leukemia.
12. Patient with history/ risk of venous thromboembolic events.
13. 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.
14. Major surgery within 2 months of screening or not recovered from any undesirable or harmful effects of any major surgery
15. 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.
16. Patient with known serum positivity for Hepatitis B, C or HIV.
17. 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.
18. 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.
19. Use of grapefruit and grapefruit containing products within 07 days prior to the first dose of study medication.
20. Participation in any investigational drug study within 30 days prior to screening.
21. Donation or loss of blood or plasma of one unit about 450 mL whole blood or 220 mL plasma in the previous 60 days.
22. History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
23. Institutionalized patient.
24. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the patient’s participation in this study.
25. Any other condition that, in the investigators 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
2 Weeks
Secondary Outcome
Outcome
TimePoints
Cminss, Tmaxss, Cavss, degree of Fluctuation, and Swing
2 Weeks
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 an open label, multicenter, randomized, two-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 Fed
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 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 of Natco 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 Fed Condition.