CTRI/2024/09/073656 [Registered on: 09/09/2024] Trial Registered Prospectively
Last Modified On:
15/02/2025
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
To assess bioequivalence between Olaparib tablets, 150mg and LYNPARZA® 150mg Olaparib tablets of AstraZeneca AB, Sweden
Scientific Title of Study
A Randomized, Open Label, Multi-Centre, Two-Treatment, Two-Period, Two-Sequence, Two-Way Cross-Over, Multiple-Dose, Steady-State, Bioequivalence (BE) Study of Test Product OLAPARIB TABLETS, 150 mg (2 × 150 mg Tablets), with LYNPARZA® 150 mg Olaparib Tablets (2 × 150 mg Tablets) of AstraZeneca AB, Sweden in Male or 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. C2A03991 Version No. 02 Date 21-May-2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dharmesh Domadia
Designation
Vice President - Global Clinical Operations
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 Jaydip Gohil
Designation
Manager - 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
9601944262
Fax
Email
jbgohil@cliantha.com
Details of Contact Person Public Query
Name
Mr Maulik Patel
Designation
Project Manager – Clinical Operations
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
09408202503
Fax
Email
mjpatel1@cliantha.com
Source of Monetary or Material Support
AET Laboratories Private Limited, Survey No.42, Gaddapotharam Village,
Kazipally Industrial Area, Sangareddy District, Telangana-502 319, India
Primary Sponsor
Name
AET Laboratories Private Limited
Address
Survey No.42, Gaddapotharam Village,
Kazipally Industrial Area, Sangareddy District, Telangana-502 319, India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Cliantha Research Ltd
TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad – 382210, Gujarat, India.
Surya Arcade, 2nd Floor, Opposite Nimani Bus Stand , Panchavati, Nashik - 422003
Nashik MAHARASHTRA
8758052774
mukul.gharote@gmail.com
Dr Anshul Agrawal
Adwaita Cancer Hospital & ICU
6th floor, Sahaj icon, Anand mahal road, Honey park, Adajan, Surat - 395009, Gujarat Surat GUJARAT
8657068668
anshul.oncology@gmail.com
Dr Velavan Kandappan
Erode Cancer Centre
Room no.-22, Ground Floor, Department of Radiation Oncology, 1/393, velavan nagar, Perundurai road, Thindal, Erode – 638012, Tamil Nadu, India Erode TAMIL NADU
9842334222
kvels@rediffmail.com
Dr Vijaya Aditya
HCG Cancer Centre
Second Floor, Research Room, Plot no: 10, Survey no: 13P, APIIC health city, Arilova, Chinnagadili, Visakhapatnam – 530040, Andhra Pradesh, India Krishna ANDHRA PRADESH
7675945176
vijayaaditya.y@hcgel.com
Dr Gopichand M
HCG City Cancer Centre
Room no.-1, Second Floor, Department of Medical Oncology, HCG City Cancer Centre, 33-25-33, CH Venkata krishnayya street, suryaraopet, Vijayawada – 520002, Andhra Pradesh, India Krishna ANDHRA PRADESH
9885256059
mgopichand@yahoo.com
Dr Prakash S S
K.R. Hospital Mysore Medical College and Research Institute
Room no. 23, Ground Floor, CRD Department, Department of Surgical Oncology, Next to Department of Radiology, K.R. Hospital, Irwin Road, Mysore – 570001, Karnataka Mysore KARNATAKA
9901000559
prakashyesyes@yahoo.com
Dr Nilesh Dhamne
Kolhapur Cancer Centre Pvt. Ltd.
Third Floor, Clinical Research Department, R.S.238, Opp. Mayur petrol pump, Gokul Shirgaon, Kolhapur, Maharashtra – 416234, India Kolhapur MAHARASHTRA
7738245698
dr.nilesh.gmc@gmail.com
Dr Koushik Chatterjee
Life Line Diagnostic Centre Cum Nursing Home
Room no. 201, Second Floor, Clinical Research Department, 4A, Wood Street, Kolkata – 700016, West Bengal Kolkata WEST BENGAL
9874357580
drkoushik.chatterjee@gmail.com
Dr K Karthikeyan
Mahatma Gandhi Medical College & Research Institute
Ground Floor, Clinical Research Room, Second Building Block-I, Pondy - Cuddalore ECR main road, Pillaiyarkuppam, Pondicherry – 607402 Pondicherry PONDICHERRY
9952017954
karthikeyankalesh@mgmcri.ac.in
Dr Ekta Vala
Medisquare Superspeciality Hospital and Research Institute
O-201,202, Gala empire, Drive - in Road, Opp. Door darshan tower, Gurukul, Ahmedabad - 380052, Gujarat Ahmadabad GUJARAT
8238034088
ektavala89@gmail.com
Dr Saju SV
Meenakshi Mission Hospital and Research Centre
Meenakshi Mission Hospital and Research Centre, Department of Oncology, lake area, Melur Road, Madurai - 625107, Tamil Nadu Madurai TAMIL NADU
7904423513
drsajusv@gmail.com
Dr Mukesh Aarya
S. P. Medical College and AG of Hospitals
Room no. 27, First Floor, Dept. of Urology, Uro-Sciences Centre, S.P. Medical College & AG of Hospitals, Bikaner – 334003, Rajasthan, India Bikaner RAJASTHAN
9782300231
mcarya@yahoo.com
Dr Nirali Trivedi
Shankus Hospitals Pvt. Ltd.
B/h Divine child school, Near shankus water park, Ahmedabad - Mehsana highway, Baliyasan, Mehsana - 382732, Gujarat Mahesana GUJARAT
8980008109
nirali_baxi81@yahoo.com
Dr Satheesh C T
Spandana Oncology Center Pvt. Ltd.
919, New no. 68, 28th main road, 9th block, Jayanagar, Bangalore - 560069, Karnataka Bangalore KARNATAKA
9242698750
drsatheeshct@gmail.com
Dr Rajender Singh Arora
Sujan Surgical Cancer Hospital & Amravati Cancer Foundation
Room No-03, Second
Floor, Sujan Surgical
Cancer Hospital &
Amravati Cancer
Foundation, 52/B,
Shankarnagar, Main
Road, Amravati -444605,
Maharashtra
Amravati MAHARASHTRA
Institutional Ethics Committee – Spandana Oncology Center
Approved
Institutional Ethics Committee Erode Cancer Centre
Approved
Institutional Ethics Committee HCG Cancer Centre
Approved
Institutional Ethics Committee HCG Curie City Cancer Centre
Approved
Institutional Ethics Committee Mysore Medical College and Research Institute
Approved
Institutional Ethics Committee of Life Line Diagnostic Centre Cum Nursing Home
Approved
Institutional Ethics Committee-Shankus Hospital
Approved
Institutional Human Ethics Committee
Approved
Kolhapur Cancer Centre Institutional Ethics Committee
Approved
Leelavati Ethics Committee
Approved
Rectitude Ethics Committee
Approved
Riddhi Medical Nursing Home – Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C56||Malignant neoplasm of ovary,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
LYNPARZA® 150mg Tablets
Dosage: 150mg,
Frequency: 2x150mg tablets twice-daily
Route of administration: Oral
Duration: 06 days
Intervention
Olaparib Tablets 150 mg
Dosage: 150mg,
Frequency: 2x150mg tablets twice-daily
Route of administration: Oral
Duration: 06 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
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 having aged 18-65 years (both inclusive).
2. Patient with body mass index (BMI) 18.5 to 30 kg/m2.
3. Patient with advanced (FIGO stages III and IV) deleterious or suspected deleterious germline and/or somatic BRCA- mutated high-grade 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 maintenance treatment with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.
OR
Monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patient with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy.
OR
Patient with deleterious or suspected deleterious gBRCAm, HER2-negative locally advanced or metastatic breast cancer. Patients should have previously been treated with an anthracycline and a taxane in the (neo) adjuvant or metastatic setting unless patients were not suitable for these treatments. Patients with hormone receptor (HR)-positive breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy.
OR
Patient with monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2-mutations (germline and/or somatic) who have progressed following prior therapy that included a new hormonal agent.
OR
In combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated.
4. Patient with established dosing regimen who are already receiving a stable dose of olaparib tablets (2 X 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. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
7. Patient with life expectancy greater than 90 days.
8. Acceptable Haematology status:
a. Haemoglobin Greater than or equal to 9 g per dL.
b. Absolute neutrophil count (ANC) Greater than or equal to 1500 cells per microliter
c. Platelet count Greater than or equal to 1, 00,000 cells per microliter
9. Calculated serum creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula)2 which is as follows:
Formula of creatinine clearance: CrCl equals to (140 – Age) x mass (kilogram weight) ÷ 72 x SCr in (mg/dL) (if female then x 85 percentage).
10. No history of addiction to any recreational drug or drug dependence or alcohol addiction within 1 year prior to screening.
11. Acceptable liver function:
a. Alanine aminotransferase Less than or equal to 2.0 x upper limit of normal (ULN)
b. Aspartate aminotransferase (AST) Less than or equal to 2.0 x upper limit of normal (ULN)
c. Total bilirubin Less than or equal to 1.5 x upper limit of normal (ULN)
d. Alkaline phosphatase Less than or equal to 2.0 x upper limit of normal (ULN)
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 3 months after last dose of study drug.
13. Female patient with postmenopausal status or Female patient of child-bearing potential should have negative serum pregnancy test and 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. Amenorrheic for 1 year or more with or without cessation of exogenous hormonal treatments.
b. 6 months to 12 months of spontaneous amenorrhea with serum FSH levels greater than 40 mIU/mL.
c. Radiation-induced oophorectomy with last menses greater than 1 year ago.
d. Chemotherapy-induced menopause with greater than 1 year interval since last menses.
e. At least 6 months post-surgery following bilateral oophorectomy with or without hysterectomy.
14. Non-smokers and non-tobacco users (i.e., having no past history of smoking and tobacco consuming for at least one year prior to screening).
15. Patient willing and able to comply with the protocol requirements for the duration of the study including undergoing treatment with study drug, attending scheduled visits and confinement and examinations.
16. Patient/LAR (Legally Acceptable Representative) willing to provide informed consent to participate in the study.
ExclusionCriteria
Details
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 who has or had drainage of ascites during the final 2 cycles of last chemotherapy regimen prior to randomisation.
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 randomisation.
5. Current or anticipated use of any prohibited medications during study participation.
6. Concomitant use of known potent CYP3A4 (Cytochrome P4503A4) inhibitors or inducer.
7. Patient with any ongoing toxicities (CTCAE (Common Terminology Criteria for Adverse Events) ≥ grade 2), with the exception of alopecia, caused by previous cancer therapy.
8. QTc (Heart Rate Corrected QT interval) greater than 450 msec (male) or greater than 470 msec (female) or family history of long QT syndrome. QT interval will be calculated with Bazetts Formula.
9. Patient with interstitial pneumonia or diffused symptomatic fibrosis of the lungs.
10. Patient with myelodysplastic syndrome/acute myeloid leukemia.
11. Patient with history/ risk of venous thromboembolic events.
12. 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.
13. Major surgery within 2 months of screening or not recovered from any undesirable or harmful effects of any major surgery.
14. 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).
15. Patient with known serum positivity for Hepatitis B, C or HIV.
16. 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. Johns wort) within 48 hours prior to the first dose of study medication.
17. Use of grapefruit and grapefruit containing products within 07 days prior to randomisation.
18. Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 90 days.
19. Patient who has received an investigational drug or participation in drug research study within 90 days prior to randomisation.
20. History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
21. 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.
22. Institutionalized patient.
23. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the patient’s participation in this study.
24. 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
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence of OLAPARIB TABLETS, 150 mg (2 x 150 mg Tablets) with LYNPARZA® 150 mg Olaparib Tablets (2 × 150 mg Tablets) of AstraZeneca AB, Sweden under fasting condition.
2 Week
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of patients.
2 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"
Phase of Trial
N/A
Date of First Enrollment (India)
15/10/2024
Date of Study Completion (India)
03/04/2025
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Date Missing
Estimated Duration of Trial
Years="0" Months="10" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Completed
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a
bioequivalence study between Olaparib tablets,
150mg manufactured by Natco Pharma for AET Laboratories Pvt. Ltd. and LYNPARZA®
150mg Olaparib tablets of AstraZeneca AB, Sweden in Male or Female Patients
with Ovarian Cancer or Breast Cancer or Prostate Cancer Under fasting
Condition.
The study will be conducted at
multiple investigator sites across India. At least 42 patients with ovarian
cancer or breast cancer or prostate cancer will be randomized in the study. The
Sponsor may decide to enroll additional patients to allow sufficient completers
(minimum of 35 evaluable patients) during the crossover period (I and II).
For the
patients who do not require the stabilization period, the approximate study
duration is approx. 62 days (±2 days) [Screening part I: 42 days, Period-I: 06
days, Period-II: 06 days, EOS/safety follow-up: 8 days (±2 days) after End of
treatment assessment].
For the
patients who require the stabilization period, the approximate study duration
is approx. 84 days (±2 days) [Screening part I: 42 days, Stabilization period:
at least 15 days, Screening part II: within 7 days, Period-I: 06 days,
Period-II: 06 days, EOS/safety follow-up: 8 days (±2 days) after End of
treatment assessment].
Patients
will undergo screening Part I which is within 42 days prior to entering the stabilization period. Patients who are not
on stable dose of Olaparib tablets 150 mg, will be entered into stabilization
period for at least 15 days.
Patients who
have completed stabilization period, will enter screening Part II within 07
days prior to randomization. The eligible patients will be randomized on day 01.
Patients who
are already on stable dose of Olaparib tablets (2 × 150 mg) twice daily for at
least 04 weeks will enter screening Part I which is within 42 days prior to
randomization. The eligible patients will be randomised on Day 01.
Upon
randomisation, patients will receive Olaparib tablets (2 x 150 mg tablets)
twice daily based on the randomization schedule in Period I (Day 01 to 06) and
in Period II (Day 07 to 12).
Safety sample will be collected after last PK blood sample collection of
the study (i.e. on Day 12) or end of treatment or at the time of early
discontinuation of a patient.