CTRI/2024/10/074896 [Registered on: 08/10/2024] Trial Registered Prospectively
Last Modified On:
25/07/2025
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
BE study of Olaparib Tablets 150 mg (2x150 mg tablets) with Lynparza® 150mg Filmtabletten Olaparib (2x150 mg tablets) in adult patients with carcinoma of the ovary, breast, prostate or adenocarcinoma of the pancreas.
Scientific Title of Study
A randomized, open label, multi-center, two-treatment, two-period, two-sequence, fully replicate, cross-over, multiple dose, steady-state, bioequivalence study of Olaparib Tablets 150 mg (2x150 mg tablets) of Alembic Pharmaceuticals Limited, India with Lynparza® 150mg Filmtabletten Olaparib (2x150 mg tablets) of AstraZeneca AB, SE-151 85 Södertälje, Schweden, in patients with ovarian cancer, breast cancer, prostate cancer or adenocarcinoma of the pancreas under fed condition.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
CO240008, Version 1.0 dated 24/Jun/2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sandeep Singh
Designation
Vice President - Clinical Operations
Affiliation
CBCC Global Research LLP
Address
TURQUOISE-IV 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura Circle
Ahmadabad GUJARAT 382210 India
Phone
9637555304
Fax
Email
sandeep.singh@cbccusa.com
Details of Contact Person Scientific Query
Name
Dr Sandeep Singh
Designation
Vice President - Clinical Operations
Affiliation
CBCC Global Research LLP
Address
TURQUOISE-IV 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura Circle
GUJARAT 382210 India
Phone
9637555304
Fax
Email
sandeep.singh@cbccusa.com
Details of Contact Person Public Query
Name
Dr Sandeep Singh
Designation
Vice President - Clinical Operations
Affiliation
CBCC Global Research LLP
Address
TURQUOISE-IV 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura Circle
GUJARAT 382210 India
Phone
9637555304
Fax
Email
sandeep.singh@cbccusa.com
Source of Monetary or Material Support
Alembic Pharmaceuticals Limited,
Alembic Road,
Vadodara - 390003,
Gujarat, India
Primary Sponsor
Name
Alembic Pharmaceuticals Limited
Address
Alembic Road,
Vadodara - 390003,
Gujarat, India
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
CBCC Global Research LLP
TURQUOISE-IV 6th Floor, Sardar Patel Ring Rd,
Opp. Apple Woods, Near Shantipura circle, Ahmedabad - 382210
Gujarat, India.
Dosage: 300 mg
Route of Administration: Oral
Duration of Therapy: 07 Days
Frequency: Twice a day
Intervention
Olaparib Tablets 150 mg (2x150 mg tablets) of Alembic Pharmaceuticals Limited, India
Dosage: 300 mg
Route of Administration: Oral
Duration of Therapy: 07 Days
Frequency: Twice a day.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1. Willing and able to provide written informed consent prior to any study-related activities being performed.
2. Male or female patients aged 18 years and older and having Body mass index (BMI) greater than or equal to 17 calculated as weight in kg per height in m2.
3. Patient who require treatment with the study drug as monotherapy.
4. Patients with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.
OR
Patients 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 should start treatment with Olaparib no later than 8 weeks after completion of their final dose of the platinum-containing regimen.
OR
Patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy
OR
Patients with germline BRCA1/2-mutations, who have 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 will 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
Patients with metastatic castration resistant prostate cancer and BRCA1/2-mutations (germline and/or somatic) who have progressed following prior therapy that included a new hormonal agent.
OR
Patients with germline BRCA1/2-mutations who have metastatic adenocarcinoma of the pancreas and have not progressed after a minimum of 16 weeks of platinum treatment within a first-line chemotherapy regimen.
5. Patients with established and well tolerated dosing regimen, who already are receiving a stable dose of Olaparib tablets (2x150 mg tablets) 300 mg twice daily.
Note: For patients who will enter stabilization period, this criteria will be evaluated at the time of screening part-02.
6. Able to swallow and retain oral medication.
7. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
8. The life expectancy of greater than 90 days.
9. Acceptable hematology status:
a. Hemoglobin greater than or equal to 9 G percent
b. Absolute neutrophil count (ANC) greater than or equal to 1500 cells per micro L
c. Absolute white blood cell (WBC) count greater than or equal to 3000 cells per micro L
d. Platelet count greater than or equal to 1, 00,000 cells per micro L
10. Acceptable liver function:
a. Alanine aminotransferase (ALT) less than or equal to 2X upper limit of normal (ULN)
b. Aspartate aminotransferase (AST) less than or equal to 2X ULN
c. Bilirubin less than 1.2 mg per dL
d. Alkaline phosphatase less than or equal to 2X ULN
Note: For patients with Hepatic or bone metastasis: Alkaline phosphatase less than 5X ULN
11. Patients with creatinine clearance greater than or equal to 60 mL per minute (using the Cockcroft-Gault Equation)
12. Female patients of child bearing potential with a negative serum pregnancy test
13. Male patients with female partners of reproductive potential must agree to use condoms from screening, during study and for at least 03 months after treatment discontinuation.
14. Women of childbearing potential, (defined as women physiologically capable of becoming pregnant) they must agree to using two effective method of contraception during study participation and for at least 06 months after the treatment discontinuation practicing two acceptable methods of contraception.
Acceptable methods of contraception are:
a. Intrauterine device (IUD) or intrauterine system
b. Double barrier method of contraception (Condom and occlusive cap or condom and spermicidal agent)
c. Male sterilization (at least 6 months prior to the screening, should be the sole male partner for that patient) plus one additional contraception method (hormonal or barrier method)
d. Female sterilization (surgical bilateral oophorectomy) or tubal ligation within at least 6 weeks prior to study participation
e. Total abstinence, partial abstinence is not acceptable.
Female patients of non-child bearing potential or female patients who have completed menopause are defined as patients who have 12 consecutive months of spontaneous amenorrhea (not amenorrhea induced by a medical condition or medical therapy) or have bilateral absence of the ovaries. Female patients of non-child bearing potential are not required to use effective method of contraception during the study.
15. Female patient must agree to not to breast feed of baby while in the study and for 1 month after taking the last dose of IP.
16. No history of addiction to any recreational drug or drug dependence or alcohol addiction.
ExclusionCriteria
Details
Patients will be excluded from the study based on the following criteria:
1. Known hypersensitivity to Olaparib or to any of the excipients.
2. Patients with known cases of pneumonitis.
3. Patients with known cases of myleodysplastic syndrome and acute myeloid
leukemia.
4. Presence of any uncontrolled systemic disease (e.g. cardiovascular disease,
hypertension, diabetes mellitus etc.) within last 6 months prior to screening.
5. Patients with deleterious or suspected deleterious gBRCAm advanced ovarian
cancer who have been treated with three or more prior lines of chemotherapy.
6. Current or anticipated use of any of the prohibited medications during study
participation (Appendix B)
7. Patients who are breastfeeding or lactating
8. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
9. Patients with surgical or other non-healing wounds.
10. Patients with known CNS metastasis.
11. Patients with history of Venous thromboembolic events within 2 months prior to
screening.
12. Patients with 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.
13. Patients who have administered any live vaccine within 28 days before the first dose of Investigational Product.
14. Has not recovered to Grade 0 or 1 toxicity from previous anticancer treatments or previous investigational agents. Exceptions are alopecia (any grade is acceptable), Hemoglobin ≥ 9 g/dL fatigue (Grade 2 is acceptable), and peripheral neuropathy (stable Grade 2 is acceptable) (Per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], v5.0).
15. Any other medical condition or serious intercurrent illness that, in the opinion of
the Investigator, may make it undesirable for the patient to participate in the study.
16. Any other condition(s) which could significantly interfere with Protocol compliance.
17. Use of grapefruit or grapefruit products, Seville oranges and its juice and recreational drugs within 72 hours prior to IP administration on Day 1.
18. Ingestion of any caffeine or xanthine containing food or beverages (tea, coffee,chocolates or cola drinks), tobacco, tobacco containing products (like pan, pan masala, gutkha) and beedi, cigarette within 48 hours prior to IP administration on Day 1.
19. Patients who have tested positive for urine alcohol test or urine screen for drugs of abuse at the time of screening or on Day 1.
20. Use of alcohol or alcoholic products within 48 hours prior to IP administration on Day 1.
21. Participation in any clinical study within 90 days before the first dose of Investigational Product.
22. Loss of ≥ 350 mL (1 unit) of blood within 90 days of enrolment in the study.
23. Patients with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare the bioavailability and characterize the pharmacokinetic profiles of Olaparib tablets 150 mg (2x150 mg tablets) of Alembic Pharmaceuticals Limited, India with Lynparza® 150mg Filmtabletten Olaparib (2x150 mg tablets) of AstraZeneca AB, SE-151 85 Södertälje, Schweden at steady state and to assess the bioequivalence.
A total of Thirty two (32) blood samples of 3.0 mL each will be collected for PK analysis in each period of the study. A total of 64 blood samples will be collected during the study.
Target Sample Size
Total Sample Size="42" Sample Size from India="42" 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 study is a randomized, open-label, multi-center,
two-treatment, two-period, two-sequence, fully replicated crossover trial
designed to evaluate the bioequivalence of Olaparib Tablets (150 mg, 2x150 mg)
produced by Alembic Pharmaceuticals Limited, India, compared with Lynparza® 150
mg Filmtabletten (2x150 mg) from AstraZeneca AB, Sweden. The trial involves
adult patients diagnosed with ovarian, breast, prostate carcinoma, or
pancreatic adenocarcinoma. Conducted under fed conditions, the study assesses
the pharmacokinetic profiles of the two formulations at steady-state to
determine if they can be considered equivalent in terms of their absorption and
overall bioavailability.