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 adult patients with carcinoma of the ovary, breast, prostate or adenocarcinoma of the pancreas under fasting condition.
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 42
- 试验地点
- 15
- 主要终点
- To compare the bioavailability and characterize
研究概览
简要总结
This study is designed to assess the bioequivalence of Olaparib Tablets 150 mg from Alembic Pharmaceuticals Limited, India, compared to Lynparza® 150 mg Filmtabletten from AstraZeneca AB, Sweden. Conducted in adult patients with carcinoma of the ovary, breast, prostate, or adenocarcinoma of the pancreas, the study uses a randomized, open-label, multi-center, two-period, two-sequence, fully replicate, cross-over design. Patients will receive both formulations under fasting conditions to determine if the pharmacokinetic profiles of the two formulations are comparable, ensuring that they can be considered bioequivalent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients will be considered eligible for the study based on the following criteria:
- •Willing and able to provide written informed consent prior to any study-related activities being performed.
- •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 m
- •Patients who requires treatment with the study drug as monotherapy.
- •Patients with documented 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 documented 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 documented germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy.
- •OR Patients with documented 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 documented 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 documented 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.
- •Patients with established and well tolerated dosing regimen, who are already receiving a stable dose of Olaparib tablets (2x150 mg tablets) 300 mg twice daily for at least 15 days.
- •Note: For patients who will enter stabilization period, this criteria will be evaluated on the day of randomization.
- •Able to swallow and retain oral medication.
- •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
- •The life expectancy of greater than 90 days.
- •Acceptable hematology status: a.
- •Hemoglobin greater than or equal to 9 G% 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
- •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 1.5 X ULN d.
- •Alkaline phosphatase less than or equal to 2X ULN Note: For patients with Hepatic or bone metastasis: Alkaline phosphatase less than 5X ULN
- •Male patients with female partners of reproductive potential must agree to use barrier contraceptives from screening, during study and for at least 03 months after treatment discontinuation.
- •Women of childbearing potential, (defined as women physiologically capable of becoming pregnant) they must agree to use two effective methods of contraception during study participation and for at least 06 months after the treatment discontinuation.
- •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-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.
- •Female patients must agree to not to breast feed baby while in the study and for 1 month after taking the last dose of IP.
- •No history of addiction to any recreational drug or drug dependence or alcohol addiction.
排除标准
- •Patients will be excluded from the study based on the following criteria:
- •Known hypersensitivity to Olaparib or to any of the excipients.
- •Patients with known cases of pneumonitis.
- •Patients with known cases of myelodysplastic syndrome and acute myeloid leukemia.
- •Presence of any uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.) within last 6 months prior to screening.
- •Patients with deleterious or suspected deleterious gBRCAm advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.
- •Current or anticipated use of any of the prohibited medications during study participation (Appendix B)
- •Patients who are breastfeeding or lactating
- •Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
- •Patients with surgical or other non-healing wounds.
- •Patients with known CNS metastasis.
- •Patients with history of Venous thromboembolic events within 2 months prior to screening.
- •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.
- •Patients who have administered any live vaccine within 28 days before the first dose of Investigational Product.
- •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).
- •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.
- •Any other condition(s) which could significantly interfere with Protocol compliance.
- •Use of grapefruit or grapefruit products, Seville oranges and its juice and recreational drugs within 72 hours prior to IP administration on Day
- •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
- •Patients who have tested positive for urine alcohol test or urine screen for drugs of abuse at the time of screening or on Day
- •Participation in any clinical study within 90 days before the first dose of Investigational Product.
- •Loss of ≥ 350 mL (1 unit) of blood within 90 days of enrolment in the study.
- •Patients with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
结局指标
主要结局
To compare the bioavailability and characterize
时间窗: Day 4,5,11,12 (Pre Dose), Day 6, 7, 13, 14 (Pre | Dose 00.00 Hrs, Post Dose - 00.25 Hrs, 00.50 | Hrs, 00.75 Hrs, 01.00 Hrs, 01.50 Hrs, 02.00 Hrs, | 02.50 Hrs, 03.00 Hrs, 03.50 Hrs, 04.00 Hrs, | 06.00 Hrs, 08.00 Hrs, 10.00 Hrs, 12.00 Hrs)
the pharmacokinetic profiles of Olaparib tablets
时间窗: Day 4,5,11,12 (Pre Dose), Day 6, 7, 13, 14 (Pre | Dose 00.00 Hrs, Post Dose - 00.25 Hrs, 00.50 | Hrs, 00.75 Hrs, 01.00 Hrs, 01.50 Hrs, 02.00 Hrs, | 02.50 Hrs, 03.00 Hrs, 03.50 Hrs, 04.00 Hrs, | 06.00 Hrs, 08.00 Hrs, 10.00 Hrs, 12.00 Hrs)
150 mg (2x150 mg tablets) of Alembic
时间窗: Day 4,5,11,12 (Pre Dose), Day 6, 7, 13, 14 (Pre | Dose 00.00 Hrs, Post Dose - 00.25 Hrs, 00.50 | Hrs, 00.75 Hrs, 01.00 Hrs, 01.50 Hrs, 02.00 Hrs, | 02.50 Hrs, 03.00 Hrs, 03.50 Hrs, 04.00 Hrs, | 06.00 Hrs, 08.00 Hrs, 10.00 Hrs, 12.00 Hrs)
Pharmaceuticals Limited, India with Lynparza®
时间窗: Day 4,5,11,12 (Pre Dose), Day 6, 7, 13, 14 (Pre | Dose 00.00 Hrs, Post Dose - 00.25 Hrs, 00.50 | Hrs, 00.75 Hrs, 01.00 Hrs, 01.50 Hrs, 02.00 Hrs, | 02.50 Hrs, 03.00 Hrs, 03.50 Hrs, 04.00 Hrs, | 06.00 Hrs, 08.00 Hrs, 10.00 Hrs, 12.00 Hrs)
150mg Filmtabletten Olaparib (2x150 mg tablets)
时间窗: Day 4,5,11,12 (Pre Dose), Day 6, 7, 13, 14 (Pre | Dose 00.00 Hrs, Post Dose - 00.25 Hrs, 00.50 | Hrs, 00.75 Hrs, 01.00 Hrs, 01.50 Hrs, 02.00 Hrs, | 02.50 Hrs, 03.00 Hrs, 03.50 Hrs, 04.00 Hrs, | 06.00 Hrs, 08.00 Hrs, 10.00 Hrs, 12.00 Hrs)
of AstraZeneca AB, SE-151 85 Södertälje,
时间窗: Day 4,5,11,12 (Pre Dose), Day 6, 7, 13, 14 (Pre | Dose 00.00 Hrs, Post Dose - 00.25 Hrs, 00.50 | Hrs, 00.75 Hrs, 01.00 Hrs, 01.50 Hrs, 02.00 Hrs, | 02.50 Hrs, 03.00 Hrs, 03.50 Hrs, 04.00 Hrs, | 06.00 Hrs, 08.00 Hrs, 10.00 Hrs, 12.00 Hrs)
Schweden at steady state and to assess the
时间窗: Day 4,5,11,12 (Pre Dose), Day 6, 7, 13, 14 (Pre | Dose 00.00 Hrs, Post Dose - 00.25 Hrs, 00.50 | Hrs, 00.75 Hrs, 01.00 Hrs, 01.50 Hrs, 02.00 Hrs, | 02.50 Hrs, 03.00 Hrs, 03.50 Hrs, 04.00 Hrs, | 06.00 Hrs, 08.00 Hrs, 10.00 Hrs, 12.00 Hrs)
bioequivalence.
时间窗: Day 4,5,11,12 (Pre Dose), Day 6, 7, 13, 14 (Pre | Dose 00.00 Hrs, Post Dose - 00.25 Hrs, 00.50 | Hrs, 00.75 Hrs, 01.00 Hrs, 01.50 Hrs, 02.00 Hrs, | 02.50 Hrs, 03.00 Hrs, 03.50 Hrs, 04.00 Hrs, | 06.00 Hrs, 08.00 Hrs, 10.00 Hrs, 12.00 Hrs)
次要结局
- To monitor the safety of the patients.(A total of Thirty two (32) blood samples of 03.0 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.)
研究者
Dr Sandeep Singh
CBCC Global Research LLP