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Trial record 1 of 1 for:    3000-01-004
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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 : April 17, 2020
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Brief Summary:
This is a two 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. Specifically, a 300 mg niraparib tablet will be compared to 3 niraparib capsules (3 × 100 mg).The Extension Phase of this study is to enable patients 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 Solid Tumor Drug: Niraparib Other: Niraparib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 244 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 : January 2, 2019
Actual Primary Completion Date : December 5, 2019
Estimated Study Completion Date : October 13, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tablet-Capsule Sequence
Single dose Niraparib Tablet (1x300mg) followed by single dose Niraparib Capsule (3x100mg) followed by optional daily dosing extension phase
Drug: Niraparib
Niraparib tablet formulation

Other: Niraparib
Niraparib capsule formulation

Experimental: Capsule-Tablet Sequence
Single dose Niraparib Capsule (3x100mg) followed by single dose Niraparib Tablet (1x300mg) followed by optional daily dosing extension phase
Drug: Niraparib
Niraparib tablet formulation

Other: Niraparib
Niraparib capsule formulation




Primary Outcome Measures :
  1. Conduct PK assessment of bioavailability of Niraparib as assessed by Maximum Concentration (Cmax) of 300 mg niraparib administered as a tablet versus capsule formulation (Stage 1 and Stage 2) . [ Time Frame: Approximately 1 year ]
  2. Obtain PK assessment of CMAX of Niraparib so as to estimate intra-subject variability. [ Time Frame: Approximately 1 year ]
  3. Conduct PK assessment of Niraparib as assessed by Maximum Concentration (Cmax) AUC of 300 mg niraparib as administered as a tablet versus capsule formulation to determine bioequivalence . [ Time Frame: Approximately 1 year ]
  4. Conduct PK assessment of Niraparib as assessed by Maximum Concentration (CMAX) from 0-t of 300 mg niraparib as administered as a tablet versus capsule formulation to determine bioequivalence. [ Time Frame: Approximately 1 year ]
  5. Conduct PK assessment of Niraparib as assessed by Maximum Concentration (CMAX) from 0-infinity of 300 mg niraparib as administered as a tablet versus capsule formulation to determine bioequivalence. [ Time Frame: Approximately 1 year ]
  6. Conduct PK assessment of bioavailability of Niraparib as assessed by Area under the plasma concentration versus time curve (AUC) of 300 mg niraparib administered as a tablet versus capsule formulation (Stage 1 and Stage 2) [ Time Frame: Approximately 1 year ]
  7. Conduct PK assessment of Niraparib as assessed by Area under the plasma concentration versus time curve (AUC) of 300 mg niraparib as administered as a tablet versus capsule formulation to determine bioequivalence . [ Time Frame: Approximately 1 year ]

Secondary Outcome Measures :
  1. The number of participants with treatment emergent adverse events (TEAEs) according to NCI CTCAE v4.03 [ Time Frame: Approximately 1 year ]
    • To evaluate the safety of single dose niraparib when administered as a tablet or capsule formulation in patients with advanced solid tumors
    • To evaluate the safety of continuously dosed niraparib in a tablet form in patients with advanced solid tumors who participate in the extension phase of the study

  2. Assess treatment related adverse events in patients who are administered a single dose of niraparib as a capsule or tablet when compared to those that are continuosly dosed with the tablet formulation in the extension phase of the study. [ Time Frame: Approximately 1 year ]
  3. AUC of metabolite of niraparib (M1) when administered as a tablet or capsule formulation in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]
  4. 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 ]


Information from the National Library of Medicine

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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

Main criteria for inclusion:

PK Phase:

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

  • Patients 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 PARP inhibitor as assessed by the Investigator.
  • ECOG performance status of 0 to 2.
  • Adequate organ function as defined below:

    • Absolute neutrophil count ≥ 1,500/μL
    • Platelets ≥ 100,000/μL
    • Hemoglobin ≥ 9 g/dL (5.6 mM)
    • Serum creatinine ≤ 1.5 × the upper limit of normal (ULN) or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation or 24-hour urine creatinine clearance.
    • Total bilirubin ≤ 1.5 × ULN except in patients with Gilbert's syndrome. Patients 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
  • Patient has recovered to Grade 1 toxicity from prior cancer therapy (a patient with Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may qualify for this study).
  • Female Patient 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 patient 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, PK Phase:

  • Known diagnosis of immunodeficiency
  • Symptomatic uncontrolled brain or leptomeningeal metastases.
  • Major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery.
  • Patient 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.
  • Patient is currently receiving a sensitive cytochrome P450 (CYP) 1A2 substrates with a narrow therapeutic index (e.g., tizanidine and theophylline) (Does not apply for Extension Phase).
  • Patient 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).
  • Patient taking proton pump inhibitors, antacids, or histamine 2 blockers within 48 hours prior to study drug administration, and/or within 6 hours after study drug administration (Does not apply for Extension Phase).
  • Patient has gastric, gastro-esophageal or esophageal cancer; patient is unable to swallow orally administered medication; or patient has gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of niraparib.
  • Patient has known active hepatic disease
  • Patient has a past or current history of chronic alcohol use.
  • Patient has significant pleural effusion or ascites that is expected to require drainage during the PK Phase (Does not apply for Extension Phase).

Key Inclusion, Extension Phase:

  • ECOG performance status of 0 to 2.
  • Adequate organ function as defined below

    • Absolute neutrophil count ≥ 1,500/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 using the Cockcroft-Gault equation or 24-hour urine creatinine clearance
    • Total bilirubin ≤ 1.5 × ULN except in patients with Gilbert's syndrome. Patients 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 patient 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 patient 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.

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
Fresno, California, United States, 93720
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, 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, 39213
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: April 17, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Zejula
Additional relevant MeSH terms:
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Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents