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Pharmacokinetic and Safety Study of Niraparib With Normal or Moderate Hepatic Impairment Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03359850
Recruitment Status : Active, not recruiting
First Posted : December 2, 2017
Last Update Posted : May 14, 2020
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Tracking Information
First Submitted Date  ICMJE October 3, 2017
First Posted Date  ICMJE December 2, 2017
Last Update Posted Date May 14, 2020
Actual Study Start Date  ICMJE February 20, 2018
Actual Primary Completion Date September 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2017)
  • Pharmacokinetic (PK) to be assessed is area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞). [ Time Frame: Approximately 2 years ]
  • Pharmacokinetic (PK) to be assessed is maximum observed plasma concentration (Cmax). [ Time Frame: Approximately 2 years ]
  • Pharmacokinetic (PK) to be assessed is time to reach Cmax (Tmax). [ Time Frame: Approximately 2 years ]
  • Pharmacokinetic (PK) to be assessed is termination elimination half-life ( t1/2). [ Time Frame: Approximately 2 years ]
  • Pharmacokinetic (PK) to be assessed is apparent total body clearance (CL). [ Time Frame: Approximately 2 years ]
  • Pharmacokinetic (PK) to be assessed is apparent terminal volume of distribution (Vz/F). [ Time Frame: Approximately 2 years ]
  • Pharmacokinetic (PK) to be assessed is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t). [ Time Frame: Approximately 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2017)
  • Evaluate safety and tolerability of niraparib when administered as a single dose in patients with normal hepatic function using Common Terminology Criteria for Adverse Events (CTCAE v.4.03). [ Time Frame: Approximately 2 years ]
  • Evaluate safety and tolerability of niraparib when administered as a single dose in patients with moderate hepatic impairment using Common Terminology Criteria for Adverse Events (CTCAE v.4.03). [ Time Frame: Approximately 2 years ]
  • Evaluate safety and tolerability of niraparib in which patients have the option to continue receiving Niraparib using Common Terminology Criteria for Adverse Events (CTCAE v.4.03). [ Time Frame: Approximately 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic and Safety Study of Niraparib With Normal or Moderate Hepatic Impairment Patients
Official Title  ICMJE An Open-Label, Non-Randomized, Multicenter Study to Determine the Pharmacokinetics and Safety of Niraparib Following a Single Oral Dose in Patients With Advanced Solid Tumors and Either Normal Hepatic Function or Moderate Hepatic Impairment
Brief Summary Niraparib (Zejula®)is extensively metabolized and eliminated primarily by hepatic and renal pathways. The purpose of this study is to evaluate pharmacokinetics and safety of niraparib in patients with moderate hepatic impairment, for the purpose of providing recommendations to guide the initial dose and dose titration in this patient population.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE
  • Ovarian Neoplasms
  • Neoplasms
  • Solid Tumor
  • Hepatic Impairment
Intervention  ICMJE Drug: Niraparib
Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for patients with tumors that harbor defects in the homologous recombination DNA repair pathway or that are driven by PARP-mediated transcription factors.
Other Name: Zejula®
Study Arms  ICMJE
  • Experimental: Normal hepatic function (Group 1):
    To evaluate the pharmocokinetics and safety of niraparib
    Intervention: Drug: Niraparib
  • Experimental: Moderate hepatic impairment (Group 2):
    To evaluate the pharmocokinetics and safety of niraparib
    Intervention: Drug: Niraparib
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: April 10, 2020)
17
Original Estimated Enrollment  ICMJE
 (submitted: November 30, 2017)
16
Estimated Study Completion Date  ICMJE October 2, 2020
Actual Primary Completion Date September 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Diagnosis and Criteria for Inclusion:

All patients:

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

  1. Patient, male or female, is at least 18 years of age.
  2. Patient has a diagnosis of advanced solid malignancy that has failed standard therapy or for which standard therapy is not likely to provide meaningful benefit, or patient has refused standard therapy.
  3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  4. Patient is able to take oral medications.
  5. Female patient, if of childbearing potential, 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 enrollment through 120 days after the last dose of study treatment, or be of non-childbearing potential. Non-childbearing potential is defined as (by other than medical reasons):

    • ≥45 years of age and has not had menses for > 1 year.
    • Amenorrheic for < 2 years without a hysterectomy Post hysterectomy, bilateral oophorectomy, or tubal ligation..

    Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.

  6. Male patient agrees to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment..
  7. Patient is able to understand the study procedures and agrees to participate in the study by providing written informed consent.

Patients with normal hepatic function (Group 1):

Patients screened for the normal hepatic function group must meet the following additional criteria to be eligible for enrollment:

  1. Patient has no history of hepatic impairment.
  2. Patient has liver function test (LFT) results within normal range:

    • Total bilirubin ≤ ULN
    • Aspartate aminotransferase (AST) ≤ ULN.
    • INR ≤1.5 X ULN unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
  3. Patient has adequate hematologic and renal function as defined below:

    • Absolute neutrophil count ≥1500/µL
    • Platelets ≥100,000/µL
    • Hemoglobin ≥9 g/dL
    • Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.

Patients with moderate hepatic impairment (Group 2):

Patients screened for the moderate hepatic impairment group must meet the following additional criteria to be eligible for enrollment:

  1. Patient has stable, moderate hepatic impairment, defined as:

    • BILI: >1.5 × to 3 × ULN, for at least 2 weeks prior to Day 1
    • AST: Any value
    • INR less than 1.8 unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
  2. Patient has hematologic and renal function as defined below:

    • Absolute neutrophil count ≥1000/µL
    • Platelets ≥75,000/µL
    • Hemoglobin ≥8 g/dL
    • Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
  3. Patient's hepatic disease is deemed stable by the Investigator

Criteria for Exclusion:

Patients will not be eligible for study entry if any of the following criteria are met:

All patients:

  1. Patient has undergone palliative radiotherapy within 1 week of study drug administration, encompassing >20% of the bone marrow.
  2. Patient is starting chemotherapy within 3 weeks of study drug administration.
  3. Patient has a known hypersensitivity to the components of niraparib or excipients
  4. Patients who received colony-stimulating factors within 2 weeks prior to the first dose of study treatment are not eligible.
  5. Patient has persistent chemotherapy associated Grade 2 or greater toxicity except for neuropathy, alopecia or fatigue.
  6. Patient has symptomatic uncontrolled brain or leptomeningeal metastases.
  7. Patient has undergone major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery.
  8. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder (other than hepatic impairment) or active, uncontrolled infection.
  9. Patient has received a transfusion (platelets or red blood cells) within 3 weeks of receiving niraparib.
  10. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment or for 3 months after the last dose of study treatment.
  11. Patient has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

    NOTE: Exclusion Criteria 12-16 apply patients participating in the PK phase of the study.

  12. Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the time of the last PK blood draw, any of the following cytochrome (CYP) 1A2 substrates: alosetron, duloxetine, melatonin, ramelteon, tacrine, tizanidine, and theophylline.
  13. Patient is unable to refrain from any intake of grapefruit or grapefruit juice within 4 days of the first administration of niraparib until the final PK sample collection.
  14. Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the last PK blood draw, 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.
  15. Patient is taking proton pump inhibitors, antacids, or histamine 2 (H2) blockers within 48 hours prior to niraparib administration, and/or within 6 hours after niraparib administration.
  16. Patient has esophagogastrointestinal disease or resection that is likely to interfere with the absorption of niraparib.

Patients with moderate hepatic impairment (Group 2):

Patients screened for the moderate hepatic impairment group who meet any of the following additional criteria will be excluded from the study:

  1. Patient has hepatic encephalopathy, severe portal hypertension and/or porto-systemic shunt.
  2. Patient has fluctuating or rapidly deteriorating hepatic function as determined by the investigator within the screening period.
  3. Patient has acute liver disease caused by drug toxicity or by an infection.
  4. Patient has biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
  5. Patient has esophageal variceal bleeding within the past 2 months.
  6. Patient is receiving anticoagulant therapy with warfarin or related coumarins.
  7. Patient has a history of hepatic transplant, systemic lupus erythematosus, or hepatic coma.
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 NCT03359850
Other Study ID Numbers  ICMJE 213354
3000-01-003 ( Other Identifier: Tesaro )
Has Data Monitoring Committee Yes
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: No
Responsible Party Tesaro, Inc.
Study Sponsor  ICMJE Tesaro, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account Tesaro, Inc.
Verification Date May 2020

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