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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 : July 25, 2022
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Niraparib Tablet Drug: Niraparib Capsule Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 236 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : November 29, 2017
Actual Primary Completion Date : December 30, 2021
Estimated Study Completion Date : May 8, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Stage 1: Tablet-Capsule Sequence
Single dose niraparib tablet followed by single dose niraparib capsule followed by optional daily dosing extension phase
Drug: Niraparib Tablet
Niraparib tablet formulation

Drug: Niraparib Capsule
Niraparib capsule formulation

Experimental: Stage 1: Capsule-Tablet Sequence
Single dose niraparib capsule followed by single dose niraparib tablet followed by optional daily dosing extension phase
Drug: Niraparib Tablet
Niraparib tablet formulation

Drug: Niraparib Capsule
Niraparib capsule formulation

Experimental: Stage 2: Tablet-Capsule Sequence
Single dose niraparib tablet followed by single dose niraparib capsule followed by optional daily dosing extension phase.
Drug: Niraparib Tablet
Niraparib tablet formulation

Drug: Niraparib Capsule
Niraparib capsule formulation

Experimental: Stage 2: Capsule-Tablet Sequence
Single dose niraparib capsule followed by single dose niraparib tablet followed by optional daily dosing extension phase
Drug: Niraparib Tablet
Niraparib tablet formulation

Drug: Niraparib Capsule
Niraparib capsule formulation

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.
Drug: Niraparib Tablet
Niraparib tablet formulation

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.
Drug: Niraparib Tablet
Niraparib tablet formulation




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Maximum observed plasma concentration (Cmax) for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  4. 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 ]
  5. Terminal elimination half-life (T1/2) for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  6. Apparent total body clearance for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  7. Apparent terminal volume of distribution for niraparib-Stages 1, 2 and 3 PK Phase [ Time Frame: Up to 168 hours post-dose ]
  8. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Number of participants with TEAEs, serious TEAEs and discontinuations due to TEAEs-Extension Phase [ Time Frame: Approximately 1 year ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03329001


Locations
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United States, California
GSK Investigational Site
Encinitas, California, United States, 92024
GSK Investigational Site
Fresno, California, United States, 93720
GSK Investigational Site
San Marcos, California, United States, 92069
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80218
United States, Connecticut
GSK Investigational Site
New Haven, Connecticut, United States, 06520
United States, Florida
GSK Investigational Site
Sarasota, Florida, United States, 34232
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30322
United States, Michigan
GSK Investigational Site
Grand Rapids, Michigan, United States, 49546
United States, Mississippi
GSK Investigational Site
Jackson, Mississippi, United States, 39216
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45267
GSK Investigational Site
Cleveland, Ohio, United States, 44106
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Dallas, Texas, United States, 75230
GSK Investigational Site
Houston, Texas, United States, 77030
GSK Investigational Site
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Tesaro, Inc.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT03329001    
Other Study ID Numbers: 213362
3000-01-004 ( Other Identifier: Tesaro )
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: July 25, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tesaro, Inc.:
PARP inhibitor
niraparib
Solid Tumor
Zejula
Additional relevant MeSH terms:
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Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents