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Completed

NCT Number: NCT03329001

Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Compared to Niraparib Capsule

This is a three stage, open label, randomized-sequence, single-crossover Phase 1 study to evaluate the relative bioavailability (BA) and Bioequivalence (BE) of niraparib administered as a tablet formulation compared to the reference capsule formulation currently marketed in the United States. Stage 3 evaluates the effect of a high-fat meal on niraparib pharmacokinetics (PK) following a single dose of the tablet. The Extension Phase of this study is to enable participants enrolled in the study to continue to receive treatment with niraparib tablets if they are tolerating it and, in the Investigator's opinion, may receive benefit.

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Key information

Conditions

Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site, Encinitas, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key inclusion criteria:

PK Phase: To be considered eligible to participate in this study, all of the following requirements must be met:

  • Participants with histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumors that have failed to respond to standard therapy, has progressed despite standard therapy, or for which no standard therapy exists, and who may benefit from treatment with a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor as assessed by the Investigator.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • Adequate organ function as defined: Absolute neutrophil count ≥ 1,500 per microliter (/μL) (For Stage 3: >=1000/μL); Platelets ≥ 100,000/μL; Hemoglobin ≥ 9 grams per deciliter (g/dL) (5.6 millimolar [mM]); Serum creatinine ≤ 1.5 × the upper limit of normal (ULN) or a calculated creatinine clearance ≥ 60 milliliters per minute (mL/min) using the Cockcroft-Gault equation or 24-hour urine creatinine clearance.; Total bilirubin ≤ 1.5 × ULN except in participants with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct bilirubin; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN unless liver metastases are present, in which case, they must be ≤ 5 × ULN.
  • Participant has recovered to Grade 1 toxicity from prior cancer therapy (a participant with Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may qualify for this study).
  • Female participant of childbearing potential is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from Screening through 180 days after the last dose of study drug.
  • Male participant agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study drug through 90 days after the last dose of study drug.
  • (For Stage 3): CNS inclusion - Based on screening brain magnetic resonance imaging indicating no evidence of brain metastasis or needing immediate local therapy.
  • Participant is able to eat a high fat meal.
  • Participant is able to fast for a minimum of 10 hours before start of visit and for an additional 4 hours after study visit.

Extension Phase:

  • ECOG performance status of 0 to 2.
  • Adequate organ function as defined: Absolute neutrophil count ≥ 1,500/μL (For Stage 3: >=1000/μL); Platelets ≥ 100,000/μL; Hemoglobin ≥ 9 g/dL (5.6 mM); serum creatinine ≤ 1.5 × the ULN or a calculated creatinine clearance ≥ 60 mL/min (For Stage 3: ≥ 30 mL/min) using the Cockcroft-Gault equation or 24-hour urine creatinine clearance; Total bilirubin ≤ 1.5 × ULN except in participant with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct bilirubin; AST and ALT ≤ 2.5 × ULN unless liver metastases are present, in which case, they must be ≤5 × ULN
  • Female participant of childbearing potential is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from Screening through 180 days after the last dose of study drug.
  • Male participant agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study drug through 90 days after the last dose of study drug.

Key Exclusion Criteria: PK Phase:

  • Known diagnosis of immunodeficiency
  • Symptomatic uncontrolled brain or leptomeningeal metastases.
  • Major surgery within 3 weeks of starting the study or participant has not recovered from any effects of any major surgery.
  • Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder; nonmalignant systemic disease; or active, uncontrolled infection.
  • Known history of myelodysplastic syndrome or acute myeloid leukemia.
  • Participant is currently taking any of the following P-glycoprotein (P-gp) inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor, and verapamil (Does not apply for Extension Phase).
  • Participant taking proton pump inhibitors, antacids, or histamine 2 blockers within 48 hours prior to study drug administration (Does not apply for Extension Phase).
  • Participant has gastric, gastro-esophageal or esophageal cancer; participant is unable to swallow orally administered medication; or participant has gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of niraparib.
  • Participant has known active hepatic disease
  • Participant has a past or current history of chronic alcohol use.
  • Participant has significant pleural effusion or ascites that is expected to require drainage during the PK Phase (Does not apply for Extension Phase).
  • For Stage 3 only: Participant is currently taking a lipase inhibitor or cholesterol absorption inhibitor, such as orlistat or ezetimibe, respectively. (Does not apply for participation in Extension Phase of this study).

Treatment and study plan

Niraparib Tablet

Drug

Niraparib tablet formulation

Niraparib Capsule

Drug

Niraparib capsule formulation

Primary outcomes

  1. Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for Niraparib-Stage 1 PK Phase

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of AUC(0-t). Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  2. Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0 to Inf]) for Niraparib-Stage 1 PK Phase

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of AUC(0 to inf). Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  3. Maximum Observed Plasma Concentration (Cmax) for Niraparib-Stage 1 PK Phase

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of Cmax. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  4. Time to Reach Maximum Observed Plasma Concentration (Tmax) for Niraparib-Stage 1 PK Phase

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of Tmax. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  5. Terminal Half-life (T1/2) for Niraparib-Stage 1 PK Phase

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of T1/2. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  6. Apparent Total Body Clearance (CL/F) for Niraparib-Stage 1 PK Phase

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of CL/F. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  7. Apparent Terminal Volume of Distribution (Vz/F) for Niraparib-Stage 1 PK Phase

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of Vz/F. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  8. AUC(0-t) for Niraparib-Stage 2 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of AUC(0-t). Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  9. AUC(0 to Inf) for Niraparib-Stage 2 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of AUC(0 to inf). Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  10. Cmax for Niraparib-Stage 2 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of Cmax. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  11. Tmax for Niraparib-Stage 2 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of Tmax. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  12. T1/2 for Niraparib-Stage 2 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of T1/2. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  13. CL/F for Niraparib-Stage 2 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of CL/F. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  14. Vz/F for Niraparib-Stage 2 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of Vz/F. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  15. AUC(0-t) for Niraparib-Stage 3 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of AUC(0-t). Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  16. AUC(0 to Inf) for Niraparib-Stage 3 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of AUC(0 to inf). Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  17. Cmax for Niraparib-Stage 3 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of Cmax. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  18. Tmax for Niraparib-Stage 3 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of Tmax. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  19. T1/2 for Niraparib-Stage 3 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of T1/2. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  20. CL/F for Niraparib-Stage 3 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of CL/F. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  21. Vz/F for Niraparib-Stage 3 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of Vz/F. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  22. Time From Administration of the Dose to the First Quantifiable Concentration (Tlag) for Niraparib-Stage 3 PK Phase

    Time frame: Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose in each treatment period

    Blood samples were collected at indicated time points for pharmacokinetic assessment of tlag. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Secondary outcomes

  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs-Stage 1 PK Phase (Periods 1 and 2 Only)

    Time frame: Up to 16 days

    An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose; results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs reported under Niraparib tablet and Niraparib capsule arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet and capsule, respectively.

  2. Number of Participants With TEAEs Leading to Discontinuation -Stage 1 PK Phase (Periods 1 and 2 Only)

    Time frame: Up to 16 days

    An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs leading to discontinuation is reported. TEAEs reported under Niraparib tablet and Niraparib capsule arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet and capsule, respectively.

  3. Number of Participants With TEAEs and Serious TEAEs-Stage 2 PK Phase (Periods 1 and 2 Only)

    Time frame: Up to 24 days

    An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that, at any dose; results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs reported under Niraparib tablet and Niraparib capsule arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet and capsule, respectively.

  4. Number of Participants With TEAEs-leading to Discontinuation Stage 2 PK Phase (Periods 1 and 2 Only)

    Time frame: Up to 24 days

    An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Number of participants with TEAEs leading to discontinuation is reported. TEAEs reported under Niraparib tablet and Niraparib capsule arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet and capsule, respectively.

  5. Number of Participants With TEAEs and Serious TEAEs-Stage 3 PK Phase (Periods 1 and 2 Only)

    Time frame: Up to 45 days

    An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that, at any dose; results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs reported under Niraparib tablets under fasted and fed arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet fasted and fed, respectively.

  6. Number of Participants With TEAEs-leading to Discontinuation Stage 3 PK Phase (Periods 1 and 2 Only)

    Time frame: Up to 45 days

    An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Number of participants with TEAEs leading to discontinuation is reported. TEAEs reported under Niraparib tablets under fasted and fed arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet fasted and fed, respectively.

  7. Number of Participants With TEAEs and Serious TEAEs - Extension Phase

    Time frame: Up to approximately 5 years 5 months

    An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that, at any dose; results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. A summary of number of participants with any TEAEs and serious TEAEs is presented. Serious TEAEs are subset of TEAEs. TEAEs were coded using the Medical Dictionary for Regulatory Affairs (MedDRA dictionary).

  8. Number of Participants With TEAEs-leading to Discontinuation - Extension Phase

    Time frame: Up to approximately 5 years 5 months

    An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. A summary of number of participants who discontinued due to any TEAEs is presented. TEAEs were coded using the Medical Dictionary for Regulatory Affairs (MedDRA dictionary).

Sponsors and collaborators

Lead sponsor

Tesaro, Inc.

Industry

Registry information

Official study title

An Open-Label, Randomized-Sequence, Multicenter, Single-Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Formulation Compared to Niraparib Capsule Formulation in Patients With Advanced Solid Tumors

Important dates

Study start
2017
Primary completion
2021
Study completion
2023
First posted
Nov 1, 2017
Registry last updated
Jul 25, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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