CTRI/2023/01/048872 [Registered on: 10/01/2023] Trial Registered Prospectively
Last Modified On:
20/06/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Crossover Trial
Public Title of Study
To compare the bioavailability of Olaparib tablets 150 mg of Qilu Pharmaceutical (Hainan) Co., Ltd. with LYNPARZA® (Olaparib) tablets 150 mg of AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850.
Scientific Title of Study
A randomized, open-label, multi-center, two-treatment, two-period, two-sequence, two-way cross over, multiple-dose, steady-state, bioequivalence (BE) study of Olaparib Tablets 150 mg of Qilu Pharmaceutical (Hainan) Co., Ltd with LYNPARZA® (Olaparib) tablets 150 mg of AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850, in male or female patients with ovarian cancer or breast cancer or pancreatic adenocarcinoma or prostate cancer.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CBCC/2022/010, Version 3.0 dated 06/Oct/2022
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
Address
Second Floor, Skoda House, Opposite L J Campus S G Highway, Sarkhej
Ahmadabad GUJARAT 380054 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
Address
Second Floor, Skoda House, Opposite L J Campus S G Highway, Sarkhej
Ahmadabad GUJARAT 380054 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
Address
Second Floor, Skoda House, Opposite L J Campus S G Highway, Sarkhej
Ahmadabad GUJARAT 380054 India
Phone
9637555304
Fax
Email
sandeep.singh@cbccusa.com
Source of Monetary or Material Support
Qilu Pharmaceutical Co. Ltd.,
No. 273-A, Nanhai Avenue, National High- Tech Zone, Haikou – 570314, China (CHN)
Primary Sponsor
Name
Qilu Pharmaceutical Co., Ltd.
Address
No. 273-A, Nanhai Avenue, National High- Tech Zone, Haikou – 570314, China (CHN)
Institutional Ethics Committee, Sparsh Hospitals and Critical Care Private Limited
Approved
Institutional Ethics Committee, Government Medical College Aurangabad
Approved
Institutional Ethics Committee, Sunshine Global Hospital
Approved
IPGMEandR Resaerch Oversight Committee
Approved
Kiran Hospital Ethics Committee
Approved
Kolhapur Cancer Centre Institutional Ethics Committee
Approved
Manavata Clinical Research Institute 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
Dosage: 150 mg,
Frequency: 2x150 mg tablets twice-daily,
Route of Administration: Oral,
Duration of Therapy: 12 Days.
Intervention
Olaparib Tablets
Dosage:150 mg,
Frequency: 2x150 mg tablets twice-daily,
Route of Administration: Oral,
Duration of Therapy: 12 Days.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
85.00 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) greaterthan 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 advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either: a deleterious or suspected deleterious BRCA mutation, and or genomic instability.
OR
Patients with a 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 human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant 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 prior endocrine therapy or be considered inappropriate for endocrine therapy.
OR
Patients 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
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 an established dosing regimen who already are receiving a stable dose of Olaparib tablets 300 mg twice daily or patients not stabilized on Olaparib treatment who are eligible to receive Olaparib therapy as per inclusion criteria 3
5. Able to swallow and retain oral medication
6. Eastern Cooperative Oncology Group (ECOG) performance status lessthan or equal to 2
7. The life expectancy of greaterthan 90 days.
8. Acceptable hematology status
a. Hemoglobin greaterthan or equal to 9 g per dL
b. Absolute neutrophil count (ANC) greaterthan or equal to 1500 cells per micro L
c. Platelet count greaterthan or equal to 1,00,000 cells per micro L
d. Absolute white blood cell (WBC) count of greaterthan or equal to 3000 cells per micro L
9. Acceptable liver function:
a. Alanine aminotransferase (ALT) lessthan or equal to 2X upper limit of normal (ULN) (lessthan or equal to 5X ULN in case of liver metastasis)
b. Aspartate aminotransferase (AST) lessthan or equal to 2X ULN (lessthan or equal to 5X ULN in case of liver metastasis)
c. Bilirubin lessthan or equal to 1.5 X ULN (lessthan or equal to 5X ULN in case of liver metastasis)
d. Alkaline phosphatase lessthan or equal to 2X ULN (lessthan or equal to 5 X ULN for bone metastasis and prostate cancer)
10. Patients with creatinine clearance by Cockcroft-Gault equation greaterthan or equal to 60 mL per minute
11. Female patients of child bearing potential with a negative serum pregnancy test
12. Male patients with female partners of reproductive potential must agree to use condoms from screening, during the study and for at least 03 months after treatment discontinuation.
13. Women of child bearing potential (defined as women physiologically capable of becoming pregnant) must agree to use an effective method of contraception during dosing and for at least 6 months after the treatment discontinuation practicing two acceptable methods of contraception
Acceptable methods of contraception are:
a. Intrauterine device (IUD) or intrauterine system
b. Hormonal method (including oral, vaginal ring, transdermal patch, implanted, or injection) started at least 7 days prior to stabilization or Day 1 plus one barrier method (cervical cap, diaphragm, contraceptive sponge, vaginal spermicide or condom)
c. A double barrier method of contraception (Condom and occlusive cap or condom and spermicidal agent)
d. 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)
e. Female sterilization (surgical bilateral oophorectomy) or tubal ligation within at least 6 weeks prior to study participation
f. 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 bilateral absence of the ovaries. Female patients of non-childbearing potential are not required to use an effective method of contraception during the study
15. No history of addiction to any recreational drug or drug dependence or alcohol addiction
ExclusionCriteria
Details
1. Known hypersensitivity to Olaparib or any of the excipients
2. Patients with history of Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML)
3. Patients with Pneumonitis
4. History or presence of any uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus, etc.)
5. Current or anticipated use of any of the prohibited medications during study participation (Appendix B)
6. Patients who are breastfeeding and lactating
7. Major surgical procedure (including periodontal) within 28 days of the first dose of Investigational Product
8. Patients with Surgical or other non-healing wounds
9. Known CNS metastasis
10. Prostate cancer patients with history of Venous thromboembolic events within 2 months prior to screening
11. 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
12. 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 reater than or equal to 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)
13. 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
14. Patients with confirmed novel coronavirus infection (COVID-19)
15. Any other condition(s) which could significantly interfere with Protocol compliance
16. Participation in any clinical study within 90 days before the first dose of Investigational Product
17. Loss of reater than or equal to 350 mL (1 unit) of blood within 90 days of enrolment in the study
18. 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 of Olaparib tablets 150 mg of Qilu Pharmaceutical (Hainan) Co., Ltd. with LYNPARZA® (Olaparib) tablets 150 mg of AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850
Day 6 & 12; Time points are Pre-dose blood sample (00.00) in the morning [Within 10 minutes prior to dosing], 0.5hrs, 1.0 hrs, 1.33hrs, 1.67hrs, 2.0hrs, 2.33hrs, 2.67hrs, 3.0hrs, 3.5hrs, 4.0hrs, 4.5hrs, 5.0hrs, 6.0hrs, 8.0hrs, 10.0hrs, 12.0hrs [Post-dose blood samples after the morning dose ± 02 minutes]
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of patients
Day 6 & 12; Time points are Pre-dose blood sample (00.00) in the morning [Within 10 minutes prior to dosing], 0.5hrs, 1.0 hrs, 1.33hrs, 1.67hrs, 2.0hrs, 2.33hrs, 2.67hrs, 3.0hrs, 3.5hrs, 4.0hrs, 4.5hrs, 5.0hrs, 6.0hrs, 8.0hrs, 10.0hrs, 12.0hrs [Post-dose blood samples after the morning dose ± 02 minutes]
Target Sample Size
Total Sample Size="48" Sample Size from India="48" 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
Multiple-dose,
steady-state, bioequivalence (BE) study of Olaparib Tablets 150 mg with primary
purpose of comparing the bioavailability of Olaparib tablets 150 mg of Qilu Pharmaceutical
(Hainan) Co., Ltd. with LYNPARZA® (Olaparib) tablets 150 mg of AstraZeneca
Pharmaceuticals LP, Wilmington, DE 19850in male or female patients with ovarian
cancer or breast cancer or pancreatic adenocarcinoma or prostate cancer.