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.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 16
- 主要终点
- 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.
研究概览
简要总结
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.
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 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Patient will be eligible for inclusion in this study only if all of the following criteria apply:
- •Male or non-pregnant, non-lactating female having aged 18-65 years (both inclusive).
- •Patient with body mass index (BMI) 18.5 to 30 kg/m
- •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.
- •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.
- •Patient having body weight ≥ 45 Kg.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Patient with life expectancy greater than 90 days.
- •Acceptable Haematology status: a.
- •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
- •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).
- •No history of addiction to any recreational drug or drug dependence or alcohol addiction within 1 year prior to screening.
- •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.
- •Alkaline phosphatase Less than or equal to 2.0 x upper limit of normal (ULN)
- •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.
- •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.
- •6 months to 12 months of spontaneous amenorrhea with serum FSH levels greater than 40 mIU/mL.
- •Chemotherapy-induced menopause with greater than 1 year interval since last menses.
- •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).
- •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.
- •Patient/LAR (Legally Acceptable Representative) willing to provide informed consent to participate in the study.
排除标准
- •Patient will not be eligible for inclusion in this study if any of the following criteria apply:
- •Patient with a known hypersensitivity to olaparib or any of the excipients of the product.
- •Patient who has or had drainage of ascites during the final 2 cycles of last chemotherapy regimen prior to randomisation.
- •Patient who are unable to swallow orally administered medication and patient with gastrointestinal disorders likely to interfere with absorption of the study medication.
- •Patient receiving any systemic chemotherapy, radiotherapy within 4 weeks prior to randomisation.
- •Current or anticipated use of any prohibited medications during study participation.
- •Concomitant use of known potent CYP3A4 (Cytochrome P4503A4) inhibitors or inducer.
- •Patient with any ongoing toxicities (CTCAE (Common Terminology Criteria for Adverse Events) ≥ grade 2), with the exception of alopecia, caused by previous cancer therapy.
- •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.
- •Patient with interstitial pneumonia or diffused symptomatic fibrosis of the lungs.
- •Patient with myelodysplastic syndrome/acute myeloid leukemia.
- •Patient with history/ risk of venous thromboembolic events.
- •Patient with symptomatic uncontrolled brain metastases.
- •Patient with cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
- •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).
- •Patient with known serum positivity for Hepatitis B, C or HIV.
- •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.
- •Use of grapefruit and grapefruit containing products within 07 days prior to randomisation.
- •Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 90 days.
- •Patient who has received an investigational drug or participation in drug research study within 90 days prior to randomisation.
- •History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
- •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.
- •Institutionalized patient.
- •Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the patient’s participation in this study.
- •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.
结局指标
主要结局
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.
时间窗: 2 Week
次要结局
- To monitor the adverse events and to ensure the safety of patients.(2 Week)
研究者
Dr Dharmesh Domadia
Cliantha Research Ltd.,