CTRI/2024/09/073640 [Registered on: 09/09/2024] Trial Registered Prospectively
Last Modified On:
16/12/2024
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
To evaluate the bioequivalence and assess the safety and tolerability of Olaparib Tablets 150 mg in patients with ovarian cancer or breast cancer or prostate cancer under fasting condition.
Scientific Title of Study
An Open-Label, Multicenter, Randomized, Two-Treatment, Two-Period, Two-Sequence, Steady-State Crossover Bioequivalence Study of Test Product Olaparib Tablets 150 mg of Dr. Reddy’s Laboratories Ltd., India with Reference Product Lynparza® (Olaparib Tablets 150 mg) of AstraZeneca Pharmaceuticals, Wilmington, USA in Adult Patients with Ovarian Cancer or Breast Cancer or Pancreatic Cancer or Prostate Cancer under Fasting Condition
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
Protocol No.: C2A04564,Version: 01,Date: 10 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
Dr. Reddy’s Laboratories Ltd, 8-2-337, Road No. 3,
Banjara Hills,
Hyderabad – 500034., India
Primary Sponsor
Name
Dr. Reddy’s Laboratories Ltd
Address
8-2-337, Road No. 3,
Banjara Hills,
Hyderabad – 500034., India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Ms Dr Reddys Laboratories Limited
M/s Dr Reddys Laboratories Limited, IPDO, Survey
no 54 Bachupally Vilage Qutubullapur Mandal (India) - 500090
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
Dept. of Urology, Uro-Science Centre, S. P. Medical College & AG of Hospitals Bikaner, 334003, Rajasthan Bikaner RAJASTHAN
9414138782
mcarya@yahoo.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 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
BP Poddar And Parvati Devi Foundation For Education
Approved
Ethics Committee S.P. Medical College
Approved
IEC Dr Dada Gujar Hospital for Mother and child
Approved
Institutional Ethics Committee Sparsh Hospital
Approved
Institutional Ethics Committee Sunshine Global Hospital
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: C25||Malignant neoplasm of pancreas, (4) ICD-10 Condition: C61||Malignant neoplasm of prostate,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Lynparza® (Olaparib) Tablets 150 mg
Dosage: 150mg Frequency: 2x150mg tablets twice-daily Route of administration: Oral Duration: 14 days
Intervention
Olaparib Tablets 150 mg
Dosage: 150mg Frequency: 2x150mg tablets twice-daily Route of administration: Oral Duration: 14 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Male or non-pregnant, non-lactating female between 18-75 years of age (both inclusive) who are willing to provide informed consent to participate in the study.
2. Patient with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are 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.
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: Patient 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 gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.
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.
3. Patient with an established dosing regimen who already are receiving a stable dose of olaparib or if naïve to olaparib, are willing to undergo at least 15 days of stabilization period with olaparib tablets, 150 mg (Dose: 600 mg/day).
4. Patient with body mass index (BMI) 18-30 kg/m2 (both inclusive).
5.Adequate bone marrow and organ function
a. Hemoglobin ≥ 9 g/dL or gm% with no blood transfusions in the previous 28 days prior to randomization
b. Absolute Neutrophil Count
c. White blood cells
d. Platelets
e. Total bilirubin ≤ 1.5 x Upper Limit Normal (ULN) or ≤ 3 x ULN in the presence of liver metastasis
f. AST/ ALT ≤ 2.5 x ULN, if liver metastases then ≤ 5 x ULN
g. Serum creatinine ≤ 1.5 x ULN
6. Calculated serum creatinine clearance
7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
8. Patient with life expectancy ≥ 14 weeks.
9. 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 3 months after last dose of study drug.
10. Female patient with postmenopausal status
or
female patient 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:
a. Postmenopausal with spontaneous amenorrhea for at least one year, or.
b. 6 months to 12 months of spontaneous amenorrhea with serum
c. Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or.
d. Total hysterectomy and an absence of bleeding for at least 3 months.
11. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations.
ExclusionCriteria
Details
1. Patient with a known hypersensitivity to olaparib or any of the excipients of the product.
2. Patient unable to swallow orally administered medication and patient with gastrointestinal disorders likely to interfere with absorption of the study medication.
3. Patient receiving any systemic chemotherapy, radiotherapy within 4 weeks before randomization.
4. Concomitant use of known strong or moderate CYP3A4 (Cytochrome P4503A4) inhibitors or inducer within 14 days before start of study medication.
5. Patient with any ongoing toxicities except alopecia
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. Patient with interstitial pneumonia or diffused symptomatic fibrosis of the lungs.
8. Patient with history of or current myelodysplastic syndrome/acute myeloid leukemia.
9. Patient with history/ risk of venous thromboembolic events.
10. 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.
11. Major surgery within 2 months of study starting and patient must have recovered from any undesirable or harmful effects of any major surgery.
12. Patient with serum positivity for Hepatitis B, C, or HIV at screening visit.
13. Consumption of any grapefruit, star fruit, grape fruit juice, seville oranges, and seville orange juice and its products within 07 days prior to first dosing of Period-I.
14. Ingestion of any alcoholic food (e.g. plum pudding, cake, chocolate containing alcohol) or beverage containing alcohol or utilize recreational drugs, caffeine or xanthine containing food or beverage within the 48 hours prior to randomization.
15. 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.
16. Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 90 days.
17. History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
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, with the exception of the cancer under treatment.
19. Participation in any investigational drug study within 30 days prior to screening.
20. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the patient’s participation in this study.
21. Any other condition that, in the investigator’s judgement, 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
Primary Endpoint(s):
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="18" Sample Size from India="18" Final Enrollment numbers achieved (Total)= "13" Final Enrollment numbers achieved (India)="13"
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 patients with Ovarian Cancer or Breast Cancer or Pancreatic
Cancer or Prostate Cancer under Fasting Condition.
Dr. Reddy’s Laboratories Ltd., 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 Dr. Reddy’s Laboratories
Ltd., India, with Reference
Product Lynparza® (Olaparib) Tablets 150 mg of AstraZeneca
Pharmaceuticals LP, Wilmington, DE 19850in adult patients with Ovarian
Cancer or Breast Cancer or Pancreatic Cancer or Prostate Cancer under Fasting
Condition.