A Study to Assess Bioequivalence of Olaparib Tablets in Patients with CancerUnder Fasting Condition

Not yet recruiting

• Conditions: Malignant (primary) neoplasm, unspecified,

• Registration Number: CTRI/2023/09/057694
• Lead Sponsor: Intas Pharmaceuticals Limited, India

Brief Summary

This is a randomized, open-label, three-treatment, three-period, multiple-dose, multi-center, crossover study to assess bioequivalence of olaparib tablets 150 mg of Intas Pharmaceuticals Ltd., India compared with Lynparza in participants with who are suffering from solid tumours under fasting condition.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-09-22
• Last Update Posted: 2023-09-30

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• 1 Must sign an ICF indicating that the participant understands the purpose of, and procedures required for the study and is willing to participate in the study.2 Man or woman participant must be at least 18 years of age, at the time of signing the informed consent.3 Body mass index (BMI) within the range 17.
• 30 kg/m2 (inclusive).4 Participants with following disease who are eligible to received olaparib monotherapy:• Maintenance treatment advanced (FIGO stages III and IV) BRCA1/2-mutated(germline and/or somatic) epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum based chemotherapy; OR• Maintenance treatment of platinum-sensitive relapsed epithelial ovarian, fallopian tube,or primary peritoneal cancer who are in response (complete or partial) to platinum based chemotherapy; OR• Adjuvant treatment of patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy; OR• Patients with 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 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 • Maintenance treatment of adult patients with 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. OR• Treatment of adult patients with 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 • Participant who are eligible to received olaparib based on the tumour-specific NCCN Guidelines®-(current version and any updates thereto).Note: Documented mutation in germline BRCA1/2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) can be assessed from any previous validated test report available for the participant. If documented BRCA1/2 test results are not available, then participants will be required to undergo BRCA1/2 testing.5 • Participants with established dosing regimen for at least 14 days who already are receiving a stable dose of olaparib tablet (2x150 mg tablets) 300 mg twice daily. OR • Participants not stabilized on olaparib/olaparib treatment naïve participants who are eligible to take olaparib tablet (2x150 mg tablets) 300 mg twice daily for dose stabilization as per PI discretion.6 An Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 at screening 7 Participant has recovered from adverse events (baseline or less than or equal to CTCAE Grade 1) due to prior anti-cancer therapy, unless AE(s) is either clinically nonsignificant or stable on supportive therapy or do not constitute a safety risk to the participant as determined by the investigator 8 Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a woman of childbearing potential (WOCBP) as defined in Appendix OR • Is a WOCBP and agrees to remain on an acceptable contraceptive method that is highly effective (with a failure rate of less than 1% per year), with low user dependency when used consistently and correctly, as described in Appendix during the stabilization phase (if applicable), during the intervention phase and for at least 6 months after the last dose of study intervention and agrees not to donate eggs ova, oocytes) for the purpose of reproduction during the stabilization phase (if applicable), during the intervention phase and for at least 6 months after the last dose of study intervention. The investigator should evaluate the effectiveness and the potential for contraceptive method failure (e.g., noncompliance, recently initiated) of the contraceptive method in relationship to the first dose of study intervention.• A WOCBP must have a negative highly sensitive serum pregnancy at screening; and urine pregnancy test within 24 hours before the first dose of investigational intervention. • If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. • Additional requirements for pregnancy testing during and after study intervention.The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.9 Male participants are eligible to participate if they agree to the following during the stabilization phase (if applicable), during the intervention phase and for at least 3 months after the last dose of study intervention:• Must agree not to plan to father a child or donate sperm for the purpose of reproduction PLUS, either of the following:• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR • Must agree to use contraception /barrier as detailed below − a male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person with female partner use of an additional highly effective contraceptive method with a failure rate of less than 1% per year 10 Participant with adequate hematologic, liver and renal function at screening visit: a ANC greater than or equal to 1500/cu.mm b Platelet count greater than or equal to 100,000/cu.mm (At screening assessment, criteria must be met without platelet transfusion within prior 1 week) c Hemoglobin greater than or equal to 9.0 g/dL (At screening assessment, criteria must be met without erythropoietin stimulating agent dependency and without packed red blood cell (pRBC) or whole blood transfusion within prior 1 week) d Estimated Creatinine clearance of >50 mL/min by the Cockcroft-Gault formula. e Alanine transaminase (ALT) and AST less than or equal to 2.5 × upper limit of normal (ULN) (less than or equal to 5×ULN for liver metastasis) f Total bilirubin less than or equal to 1.5×ULN g Alkaline phosphatase less than or equal to 2.5x ULN (less than or equal to 5×ULN for bone metastasis and less than or equal to 4xULN for liver metastasis) 11 Willing and able to adhere to the lifestyle restrictions specified in this protocol.

Exclusion Criteria

• Any potential participant who meets any of the following criteria will be excluded from participating in the study: 1 Documented medical history of uncontrolled, clinically significant intercurrent cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances or any other medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol specified assessments.
• 2 Known allergies, hypersensitivity, or intolerance to any of the study interventions, or components/ excipients thereof (refer to the SmPC), or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.Had major surgical procedure within 4 weeks before screening, or will not have fully recovered from surgical procedure, or has surgical procedure planned during the time the participant is expected to participate in the study.
• NOTE: Participants with any planned surgical procedure under local anaesthesia only may participate if they agree to seek prior approval from the investigator and such planned procedure is not expected to prevent, limit, or confound the protocol-specified assessments as assessed by the investigator.4 History or current evidence of pneumonitis as assessed by the investigator clinically or radiologically from the most recent scans.5 Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of investigational intervention.6 Positive hepatitis C antibody test result at screening or within 3 months prior to starting investigational intervention.
• NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained.
• 7 Has known human immunodeficiency virus (HIV) seropositive status, or positive HIV antibody test at screening.8 History of drug or alcohol abuse within 1 year prior to screening or positive test result(s) for alcohol or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines) at baseline.9 History of malignancy except cancer under study within the past 5 years except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
• The time requirement also does not apply to participants basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers who underwent successful definitive resection with no evidence of metastatic disease which is considered cured with minimal risk of recurrence.10 Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the study 11 Past or intended use of any disallowed therapies as noted in Section 6.9,Prior and Concomitant Therapy 12 Received an investigational intervention or used an invasive investigational medical device within 30 days or 5 half-lives prior to the first dose of study intervention, whichever is longer, or is currently enrolled in an investigational study.
• 13 Unable to swallow solid, oral dosage forms whole with the aid of water (participants may not chew, divide, dissolve, or crush the investigational intervention).14 Donated blood or blood products or had substantial loss of blood (more than 350 mL) within 3 months before the first dose of study intervention or intention to donate blood or blood products during the study.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
• Pharmacokinetic Parameters: AUC0-τ,ss & Cmax,ss	From post-dose (morning dose) on Day 06, Day 12 & Day 18:

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic Parameters: Tmax,ss, Cavg,ss, CÏ„,ss, Cmin,ss, Swing & %Fluctuation,	Cpd,

Trial Locations

Locations (8)

HCC Multispeciality Hospital LLP; 🇮🇳 Ahmadabad, GUJARAT, India

Indrayani Hospital & Cancer Institute; 🇮🇳 Pune, MAHARASHTRA, India

Jaipur National University Institute for Medical Science and Research Centre; 🇮🇳 Jaipur, RAJASTHAN, India

Kiran Hospital Multi Super Speciality hospital & Research Center; 🇮🇳 Surat, GUJARAT, India

Lifeline Diagnostic Centre cumm Nursing Home; 🇮🇳 Kolkata, WEST BENGAL, India

MNJ Institute of oncology and Regional Cancer Center; 🇮🇳 Hyderabad, TELANGANA, India

Narayana Multi-speciality Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Sterling Hospital; 🇮🇳 Rajkot, GUJARAT, India

HCC Multispeciality Hospital LLP

🇮🇳Ahmadabad, GUJARAT, India

Dr Akash Patel

Principal investigator

9601987566

drakash.cr@gmail.com