CTRI/2021/08/035525 [Registered on: 09/08/2021] Trial Registered Prospectively
Last Modified On:
12/10/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
Bioequivalence study of Olaparib Tablets 150 mg with LYNPARZA® (Olaparib) tablets 150 mg in male or female patients with ovarian cancer or breast cancer or prostate cancer.
Scientific Title of Study
A randomized, open label, multi-center, two-treatment, three period, three-sequence, reference replicate, multiple dose, steady-state, bioequivalence (BE) study of Olaparib Tablets 150 mg (2x150 mg tablets) of Natco Pharma Limited with LYNPARZA® (Olaparib) tablets 150 mg (2x150 mg tablets) of AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850, in male or female patients with ovarian cancer or breast cancer or prostate cancer.
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
CBCC/2020/032, Version: 1.0 dated: 02/Dec/2020
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
Second Floor, Skoda House, Opposite L J Campus S G Highway, Sarkhej, Ahmedabad, Gujarat– 382210, India
Ahmadabad GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
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
Second Floor, Skoda House, Opposite L J Campus S G Highway, Sarkhej, Ahmedabad, Gujarat– 382210, India
GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
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
Second Floor, Skoda House, Opposite L J Campus S G Highway, Sarkhej, Ahmedabad, Gujarat– 382210, India
Amravati Ethics Committee Sujan Surgical Cancer Hospital And Research
Approved
Ethics Committee MS Ramaiah Medical College and Hospital
Approved
Ethics Committee GSVM Medical College
Submittted/Under Review
Ethics Committee NSCBC research institute
Approved
IEC-KCHRC
Approved
IEC-MMC and RI and Associated Hospital
Submittted/Under Review
IEC-Saveetha Medical College Hospital
Approved
Institutional Ethics Committee -HCG Curie CCC
Approved
Institutional Ethics Committee Deenanath Mangeshkar Hospital and Research Centre
Approved
Institutional Ethics Committee Erode Cancer Centre
Approved
Institutional Ethics Committee Government Medical College Aurangabad Ethics committee
Approved
Institutional Ethics Committee HCG Cancer Centre
Approved
Institutional Ethics Committee Hindu Mission Hospital
Approved
Institutional Ethics Committee KLE’S Dr. Prabhakar Kore Hospital and Medical Research Centre
Approved
Institutional Ethics Committee Sparsh Hospital and Critical Care
Approved
Mahatma Gandhi Cancer Hospital & Research Institute Institutional Review Board
Approved
Manavta Clinical Research Institute Ethics Committee
Approved
Nirmal Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
LYNPARZA® (Olaparib) tablets 150 mg, Distributed By: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850, USA
Dose: 600mg per Day,
Frequency: Twice Daily,
Route of administration: Oral,
Duration of Therapy:12 Days
Intervention
Olaparib Tablets 150 mg, Manufactured by: Natco Pharma Limited, India
Dose: 600mg per day,
Frequency: Twice Daily,
Route of administration: Oral,
Duration of Therapy: 06 Days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Patients will be considered eligible for the study based on the following criteria:
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. Patients 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 platinum-based chemotherapy.
OR
Patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy
OR
Patients with deleterious or suspected deleterious gBRCAm advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy
OR
Patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. 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
Patients 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.
4. Patients with established dosing regimen who are already receiving a stable dose of olaparib tablets (2x150 mg tablets) 300 mg twice daily.
5. Able to swallow and retain oral medication.
6. Eastern Cooperative Oncology Group (ECOG) performance status Less than or equal to 2.
7. Life expectancy of Greater than 90 days.
8. Acceptable hematology status:
a. Hemoglobin 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. Acceptable liver function:
a. Alanine aminotransferase Less than or equal to 2X upper limit of normal
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
10. Patients with creatinine clearance Greater than or equal to 60 mL per minute.
11. Female patients with negative serum pregnancy test
12. 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.
13. Women of child bearing potential, (defined as women physiologically capable of becoming pregnant) they must agree to use effective method of contraception during dosing and for at least 06 months after the treatment discontinuation) practicing two acceptable methods of contraception.
Acceptable methods of contraception are:
a. Intrauterine device 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.
14. Female patients of non-childbearing 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-childbearing potential are not required to use effective method of contraception during the study.
15. 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 Pneumonitis.
3. History or presence of any uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.).
4. Current or anticipated use of any of the prohibited medications during study participation (Appendix B)
5. Patients who are breastfeeding and lactating.
6. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
7. Patients with Surgical or other non-healing wounds.
8. Known CNS metastasis.
9. 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.
10. 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 Greather than or equal to9 g per 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).
11. 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.
12. Patient tested positive for Coronavirus infection (COVID-19).
13. Any other condition(s) which could significantly interfere with Protocol compliance.
14. Participation in any clinical study within 90 days before the first dose of Investigational Product.
15. Loss of Greather than or equal to350 mL (1 unit) of blood within 90 days of enrolment in the study.
16. 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 assess the bioequivalence and characterize the pharmacokinetic profiles of Olaparib tablets 150 mg (2x150 mg tablets) of Natco Pharma Limited with LYNPARZA® (Olaparib) tablets 150 mg (2x150 mg tablets) of AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850
A total of forty-five (45) blood PK blood samples of 3.0 mL from each patient will be
Collected during the study duration. Sample will be collected on day 4, 5, 6, 10, 11, 12, 16, 17, 18.
Secondary Outcome
Outcome
TimePoints
To assess the safety and tolerability of test product compared to reference product by monitoring adverse events
A total of forty-five (45) blood PK blood samples of 3.0 mL from each patient will be
Collected during the study duration. Sample will be collected on day 4, 5, 6, 10, 11, 12, 16, 17, 18.
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
Natco Pharma Limited. has developed the test product Olaparib tablets 150 mg similar to that of the reference product LYNPARZA® (Olaparib) tablets 150 mg of AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 for US regulatory submission. This study is being conducted to characterize the pharmacokinetic profile of Sponsor’s test product in comparison to the reference product after multiple oral dose administration in male or female patients with ovarian cancer or breast cancer or prostate cancer to assess the bioequivalence.
Study has been designed as per USFDA OGD recommendation