Breast Cancer, Ovarian Cancer
Conditions
Keywords
cancer of the ovaries,, female reproductive cancer,, ovarian carcinoma,, female breast cancer
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.
Interventions
DRUGOlaparib tablets, 150 mg
Olaparib tablets, 150 mg of Lek Pharmaceuticals d.d., Slovenia
DRUGLynparza® (olaparib) tablets 150 mg
Lynparza® (olaparib) tablets 150 mg Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, Delaware (DE).
Sponsors
Sandoz
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 85 Years
Healthy volunteers
No
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. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration During the Dosing Interval at Steady State (CmaxSS) | Pre-dose (0.00 hr) on day 1,6,7,8,14,15 and 16 and Post-dose on day 8 and day 16 | 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 Breast Cancer Gene (BRCA) mutated ovarian cancer, recurrent ovarian cancer or metastatic breast cancer. |
| Area Under the Plasma Concentration Versus Time Curve for One Dosing Interval at Steady State (AUC(0-t)ss) | Pre-dose (0.00 hr) on day 1,6,7,8,14,15 and 16 and Post-dose on day 8 and day 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Adverse Events | up to Day 24 | To monitor the serious adverse events of patients and to assess safety of each of the two formulations. |
| Number of Adverse Events | up to Day 24 | To monitor the adverse events of patients and to assess safety of each of the two formulations. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Olaparib Tablets, 150 mg, Then Lynparza® (Olaparib) Tablets 150 mg participants will receive 2 x 150 mg Olaparib tablets twice daily for 16 days in a crossover design
Olaparib tablets, 150 mg: Olaparib tablets, 150 mg of Lek Pharmaceuticals d.d., Slovenia Lynparza® (olaparib) tablets 150 mg: Lynparza® (olaparib) tablets 150 mg Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE | 35 |
| Lynparza® (Olaparib) Tablets 150 mg, Then Olaparib Tablets, 150 mg participants will receive 2 x 150 mg Olaparib tablets twice daily for 16 days in a crossover design
Lynparza® (olaparib) tablets 150 mg: Lynparza® (olaparib) tablets 150 mg Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE Olaparib tablets, 150 mg: Olaparib tablets, 150 mg of Lek Pharmaceuticals d.d., Slovenia | 35 |
| Total | 70 |
Baseline characteristics
| Characteristic | Olaparib Tablets, 150 mg, Then Lynparza® (Olaparib) Tablets 150 mg | Lynparza® (Olaparib) Tablets 150 mg, Then Olaparib Tablets, 150 mg | Total |
|---|---|---|---|
| Age, Continuous | 47.77 years STANDARD_DEVIATION 8.977 | 50.74 years STANDARD_DEVIATION 10.59 | 49.26 years STANDARD_DEVIATION 9.859 |
| BMI | 25.27 Kg/m^2 STANDARD_DEVIATION 3.48 | 25.62 Kg/m^2 STANDARD_DEVIATION 3.444 | 25.44 Kg/m^2 STANDARD_DEVIATION 3.441 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 35 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 35 Participants | 35 Participants | 70 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 35 participants | 35 participants | 70 participants |
| Sex: Female, Male Female | 35 Participants | 35 Participants | 70 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 69 |
| other Total, other adverse events | 19 / 70 | 17 / 69 |
| serious Total, serious adverse events | 0 / 70 | 1 / 69 |
Outcome results
Primary
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.
Time frame: Pre-dose (0.00 hr) on day 1,6,7,8,14,15 and 16 and Post-dose on day 8 and day 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olaparib Tablets, 150 mg | Area Under the Plasma Concentration Versus Time Curve for One Dosing Interval at Steady State (AUC(0-t)ss) | 59480.137 hr*ng/mL | Standard Deviation 25073.7016 |
| Lynparza® (Olaparib) Tablets 150 mg | Area Under the Plasma Concentration Versus Time Curve for One Dosing Interval at Steady State (AUC(0-t)ss) | 64104.218 hr*ng/mL | Standard Deviation 29492.0018 |
Primary
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 Breast Cancer Gene (BRCA) mutated ovarian cancer, recurrent ovarian cancer or metastatic breast cancer.
Time frame: Pre-dose (0.00 hr) on day 1,6,7,8,14,15 and 16 and Post-dose on day 8 and day 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olaparib Tablets, 150 mg | Maximum Plasma Concentration During the Dosing Interval at Steady State (CmaxSS) | 10395.085 ng/mL | Standard Deviation 3374.48 |
| Lynparza® (Olaparib) Tablets 150 mg | Maximum Plasma Concentration During the Dosing Interval at Steady State (CmaxSS) | 9676.278 ng/mL | Standard Deviation 2845.1708 |
Secondary
Number of Adverse Events
To monitor the adverse events of patients and to assess safety of each of the two formulations.
Time frame: up to Day 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib Tablets, 150 mg | Number of Adverse Events | 43 Number of Adverse Events |
| Lynparza® (Olaparib) Tablets 150 mg | Number of Adverse Events | 37 Number of Adverse Events |
Secondary
Number of Serious Adverse Events
To monitor the serious adverse events of patients and to assess safety of each of the two formulations.
Time frame: up to Day 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib Tablets, 150 mg | Number of Serious Adverse Events | 0 Number of Serious Adverse Events |
| Lynparza® (Olaparib) Tablets 150 mg | Number of Serious Adverse Events | 1 Number of Serious Adverse Events |