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Trial record 1 of 1 for:    03329001
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Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Compared to Niraparib Capsule

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ClinicalTrials.gov Identifier: NCT03329001
Recruitment Status : Active, not recruiting
First Posted : November 1, 2017
Last Update Posted : September 9, 2022
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Tracking Information
First Submitted Date  ICMJE October 23, 2017
First Posted Date  ICMJE November 1, 2017
Last Update Posted Date September 9, 2022
Actual Study Start Date  ICMJE November 29, 2017
Actual Primary Completion Date December 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2021)
  • Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC[0-t]) for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  • Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC[0 to inf]) for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  • Maximum observed plasma concentration (Cmax) for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  • Time to reach maximum observed plasma concentration (Tmax) for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  • Terminal elimination half-life (T1/2) for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  • Apparent total body clearance for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  • Apparent terminal volume of distribution for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  • Time from administration of the dose to the first quantifiable concentration (Tlag) for niraparib-Stage 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 30, 2017)
  • Stage 1: Intrasubject variability of niraparib AUC [ Time Frame: Approximately 1 year ]
  • Stage 1: Intrasubject variability of niraparib Cmax [ Time Frame: Approximately 1 year ]
  • Stage 2: Relative bioavailability (BA) of 300 mg niraparib administered as a tablet (1 × 300 mg) formulation versus capsule (3 × 100 mg) formulation [ Time Frame: Approximately 1 year ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2021)
  • Number of participants with treatment emergent adverse events (TEAEs), serious TEAEs and discontinuations due to TEAEs-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 54 days ]
  • Number of participants with TEAEs, serious TEAEs and discontinuations due to TEAEs-Extension Phase [ Time Frame: Approximately 1 year ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2017)
  • The number of participants with treatment emergent adverse events (TEAEs) according to NCI CTCAE v4.03 [ Time Frame: Approximately 1 year ]
  • AUC of a metabolite of niraparib (M1) when administered as a tablet or capsule formulation in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]
  • Cmax of a metabolite of niraparib (M1) when administered as a tablet or capsule formulation in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Compared to Niraparib Capsule
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: Niraparib Tablet
    Niraparib tablet formulation
  • Drug: Niraparib Capsule
    Niraparib capsule formulation
Study Arms  ICMJE
  • Experimental: Stage 1: Tablet-Capsule Sequence
    Single dose niraparib tablet followed by single dose niraparib capsule followed by optional daily dosing extension phase
    Interventions:
    • Drug: Niraparib Tablet
    • Drug: Niraparib Capsule
  • Experimental: Stage 1: Capsule-Tablet Sequence
    Single dose niraparib capsule followed by single dose niraparib tablet followed by optional daily dosing extension phase
    Interventions:
    • Drug: Niraparib Tablet
    • Drug: Niraparib Capsule
  • Experimental: Stage 2: Tablet-Capsule Sequence
    Single dose niraparib tablet followed by single dose niraparib capsule followed by optional daily dosing extension phase.
    Interventions:
    • Drug: Niraparib Tablet
    • Drug: Niraparib Capsule
  • Experimental: Stage 2: Capsule-Tablet Sequence
    Single dose niraparib capsule followed by single dose niraparib tablet followed by optional daily dosing extension phase
    Interventions:
    • Drug: Niraparib Tablet
    • Drug: Niraparib Capsule
  • Experimental: Stage 3: High fat meal-fasted sequence
    Single dose niraparib tablet with a high fat meal followed by single dose of niraparib tablet in a fasted state.
    Intervention: Drug: Niraparib Tablet
  • Experimental: Stage 3: Fasted-high fat meal sequence
    Single dose niraparib tablet in a fasted state followed by single dose Niraparib tablet with a high fat meal.
    Intervention: Drug: Niraparib Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 18, 2022)
236
Original Estimated Enrollment  ICMJE
 (submitted: October 30, 2017)
80
Estimated Study Completion Date  ICMJE May 8, 2023
Actual Primary Completion Date December 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03329001
Other Study ID Numbers  ICMJE 213362
3000-01-004 ( Other Identifier: Tesaro )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Current Responsible Party Tesaro, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Tesaro, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account Tesaro, Inc.
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP