Clinical trial NCT05258747: 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 Breast Cancer Gene (BRCA) Mutated Ovarian Cancer, Recurrent Ovarian Cancer or Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Breast Cancer
Keywords: cancer of the ovaries,
female reproductive cancer,
ovarian carcinoma,
female breast cancer
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
First posted: 2022-02-28
Enrollment: 70
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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 Human epidermal growth factor receptor 2 (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/m\^2 (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 Investigational Medicinal Product (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. John"s 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.

Primary outcomes:
measure: Maximum Plasma Concentration During the Dosing Interval at Steady State (CmaxSS)
timeFrame: Pre-dose (0.00 hr) on day 1,6,7,8,14,15 and 16 and Post-dose on day 8 and day 16
measure: Area Under the Plasma Concentration Versus Time Curve for One Dosing Interval at Steady State (AUC(0-t)ss)
timeFrame: 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 outcomes:
measure: Number of Serious Adverse Events
timeFrame: up to Day 24
measure: Number of Adverse Events
timeFrame: up to Day 24
Other outcomes:
Locations:
city: Vijayawada
country: India
facility: Sandoz Investigative Site
state: Andhra Pradesh
Study officials:
affiliation: Sandoz
name: Sandoz
role: STUDY_DIRECTOR
References: