A Crossover Bioequivalence Study of Olaparib Tablets, 150 mg (Lek Pharmaceuticals d.d.) and Lynparza® (Olaparib) Tablets 150 mg (AstraZeneca Pharmaceuticals LP), in Patients With BRCA Mutated Ovarian Cancer, Recurrent Ovarian Cancer or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This is a two-way crossover bioequivalence study between test and reference product in patients diagnosed with BRCA mutated ovarian cancer, recurrent ovarian cancer or metastatic breast cancer.

Detailed Description
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This is a two-way crossover bioequivalence study between test and reference product in patients diagnosed with BRCA mutated ovarian cancer, recurrent ovarian cancer or metastatic breast cancer. Patients will be enrolled after providing written informed consent and treatments will be allocated to patient by carrying out randomization using statistical techniques. Patients that are already on a stable dose of Lynparza® (olaparib) tablets and have met the eligibility criteria will be directly randomized for participation in the study. After randomization patients will receive either test or reference product in a crossover manner based on the randomization schedule. Patients will receive the dose of 300 mg twice daily for 16 days in a crossover design. In period-I (Day 1 to Day 8), patients will receive either Test product or Reference product for 8 days based on the randomization schedule. In period-II (Day 9 to Day 16), patients will be switched to the other product for a second period of 8 days.

Official Title
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A Randomized, Open Label, Multi-centre, Two-treatment, Two-period, Two-sequence, Two-stage, Multiple Dose, Steady-state, Crossover, Bioequivalence Study of Olaparib Tablets, 150 mg (Lek Pharmaceuticals d.d.) and Lynparza® (Olaparib) Tablets 150 mg (AstraZeneca Pharmaceuticals LP), in Patients With BRCA Mutated Ovarian Cancer, Recurrent Ovarian Cancer or Metastatic Breast Cancer Under Fasting Condition

Conditions
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Ovarian Cancer, Breast Cancer

Intervention / Treatment
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* Drug: Olaparib tablets, 150 mg
* Drug: Lynparza® (olaparib) tablets 150 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian Cancer maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. OR Maintenance Treatment of Recurrent Ovarian Cancer maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. OR Advanced Germline BRCA-mutated Ovarian Cancer After 3 or More Lines of Chemotherapy treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. OR Germline BRCA-mutated HER2-negative Metastatic Breast Cancer treatment of adult 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. Non-smoking, non-pregnant, non-lactating female patient ≥18 years of age with a body mass index (BMI) in the range of 18.50 to 30.00 kg/m2 (both inclusive). Able to give written informed consent for participation in the trial and willing to adhere to protocol requirements. Patient having an estimated survival of at least 3 months Adequate organ and bone marrow function based upon the following laboratory criteria at the time of eligibility assessment prior to dosing in period 1 Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Women of non child bearing potential with documented evidence of hysterectomy / bilateral salpingectomy / bilateral oophorectomy at least 6 months prior to IMP administration) or postmenopausal for at least 12 consecutive months. OR Women of child bearing potential must have negative pregnancy test at screening visit and before randomization and must agree to use an effective method of avoiding pregnancy (including oral, transdermal or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to IMP administration] sexual partner) for at least 4 weeks prior to IMP administration, during the study and up to 6 months after the last dose of IMP. Cessation of birth control after this point should be discussed with a responsible physician. Exclusion Criteria: History of known hypersensitivity to olaparib or its components which, in the opinion of the Investigator, would compromise the safety of the patient or the results of the study. Usage of strong and moderate CYP3A4 inhibitors (e.g., cimetidine, ciprofloxacin, grapefruit juice) or strong and moderate CYP3A4 inducers (e.g., carbamazepine, phenytoin, St. Johns Wort, rifampicin) within 30 days prior to first dosing in Period 01. Pregnant or lactating females. History or presence of clinically significant lactose, galactose, or fructose intolerance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olaparib tablets, 150 mg<br>participants will receive 2 x 150 mg Olaparib tablets twice daily for 16 days in a crossover design | Drug: Olaparib tablets, 150 mg<br>* Olaparib tablets, 150 mg of Lek Pharmaceuticals d.d., Slovenia<br>|
| Active Comparator: Lynparza® (olaparib) tablets 150 mg<br>participants will receive 2 x 150 mg Olaparib tablets twice daily for 16 days in a crossover design | Drug: Lynparza® (olaparib) tablets 150 mg<br>* Lynparza® (olaparib) tablets 150 mg Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration during the dosing interval at steady state (CmaxSS) | To assess the pharmacokinetics and establish bioequivalence of the Test Product (Olaparib tablets, 150 mg) relative to that of Reference Product (Lynparza® (olaparib) tablets 150 mg) in patients with BRCA mutated ovarian cancer, recurrent ovarian cancer or metastatic breast cancer. | Pre-dose (0.00 hr) on day 1,6,7,8,14,15 and 16 and Post-dose on day 8 and day 16 | 
| Area under the plasma concentration versus time curve for one dosing interval at steady state (AUC(0-t)ss) | To assess the pharmacokinetics and establish bioequivalence of the Test Product (Olaparib tablets, 150 mg) relative to that of Reference Product (Lynparza® (olaparib) tablets 150 mg) in patients with BRCA mutated ovarian cancer, recurrent ovarian cancer or metastatic breast cancer. | Pre-dose (0.00 hr) on day 1,6,7,8,14,15 and 16 and Post-dose on day 8 and day 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events and serious adverse events | To monitor the adverse events of patients and to assess safety of each of the two formulations. | up to Day 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer of the ovaries,, female reproductive cancer,, ovarian carcinoma,, female breast cancer