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

• Sponsor: Tesaro, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03359850
• Collaborator: (none)
• Enrollment: 17
• Locations: 5
• Arms: 2
• Actual Duration (Months): 28.1
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Neoplasms; Neoplasms; Solid Tumor; Hepatic Impairment	Drug: Niraparib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Feb 20, 2018
• Actual Primary Completion Date: Sep 16, 2019
• Actual Study Completion Date: Jun 24, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Normal hepatic function (Group 1): To evaluate the pharmocokinetics and safety of niraparib	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 Names: Zejula®
Experimental: Moderate hepatic impairment (Group 2): To evaluate the pharmocokinetics and safety of niraparib	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 Names: Zejula®

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Niraparib and Its Major Metabolite (M1) During PK Phase [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1]

   Blood samples were collected at indicated time points to evaluate AUC (last) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.

2. Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1]

   Blood samples were collected at indicated time points to evaluate AUC (0-infinity) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.

3. Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1]

   Blood samples were collected at indicated time points to evaluate Cmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.

4. Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1]

   Blood samples were collected at indicated time points to evaluate tmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.

5. Terminal Half-life (t½) of Niraparib and M1 During PK Phase [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1]

   Blood samples were collected at indicated time points to evaluate t1/2 of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.

6. Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1]

   CL/F is calculated as Dose/(AUC 0-inf). Blood samples were collected at indicated time points to evaluate CL/F of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. Not applicable (NA) indicates that CL/F could not be measured for M1 since the dose of metabolite is unknown and only known dose is that of parent niraparib.

Secondary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAE) Including Non-serious Adverse Events (Non-SAEs), Serious Adverse Events (SAEs) and Discontinuations Due to AEs During PK Phase [Up to Day 8]

   An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as 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 disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are 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.

2. Change From Baseline in Hemoglobin (Hb) During PK Phase [Baseline and at Day 8]

   Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

3. Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase [Baseline and Day 8]

   Blood samples were collected to analyze hematology parameters:Leukocyte, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

4. Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase [Baseline and Day 8]

   Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

5. Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase [Baseline and Day 8]

   Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

6. Change From Baseline in Clinical Chemistry Parameter of Amylase During PK Phase [Baseline and Day 8]

   Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

7. Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase [Baseline and Day 8]

   Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

8. Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase [Baseline and Day 8]

   Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

9. Change From Baseline in Weight During PK Phase [Baseline, Day 2 and Day 8]

   Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

10. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase [Baseline, Day 2 and Day 8]

    Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

11. Change From Baseline in Pulse Rate During PK Phase [Baseline, Day 2 and Day 8]

    Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

12. Change From Baseline in Body Temperature During PK Phase [Baseline, Day 2 and Day 8]

    Vital sign including body temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.

13. Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase [Up to 28 months]

    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as 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 disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are 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.

14. Change From Baseline in Hb During Extension Phase [Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days)]

    Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

15. Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase [Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days)]

    Blood samples were collected to analyze hematology parameters: Lymphocytes, Leukocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

16. Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase [Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)]

    Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

17. Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase [Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)]

    Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

18. Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase [Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)]

    Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

19. Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase [Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)]

    Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

20. Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase [Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)]

    Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

21. Change From Baseline in Weight During Extension Phase [Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)]

    Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

22. Change From Baseline in SBP and DBP During Extension Phase [Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)]

    Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

23. Change From Baseline in Pulse Rate During Extension Phase [Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)]

    Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

24. Change From Baseline in Temperature During Extension Phase [Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)]

    Vital sign including temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

Other Outcome Measures

1. Plasma Protein Unbound Fraction (Fu) of Niraparib and M1 During PK Phase [Pre-dose, 3 hours and 168 hours post dose Day 1]

   Unbound fraction is the unbound concentration of niraparib and M1 in plasma divided by total concentration. This analysis was planned but not performed due to insufficient participants with data

2. Clearance of Unbound Niraparib and M1 (CLfu/F) During PK Phase [Pre-dose, 3 hours and 168 hours post dose Day 1]

   CLfu/F is the clearance for unbound niraparib and M1. This analysis was planned but not performed due to insufficient participants with data

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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..

2. 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.

1. 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.

1. 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.

1. 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.

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Los Angeles	California	United States	90033
2	GSK Investigational Site	Newport Beach	California	United States	92663
3	GSK Investigational Site	Aurora	Colorado	United States	80045
4	GSK Investigational Site	Atlanta	Georgia	United States	30322
5	GSK Investigational Site	Houston	Texas	United States	77030

Sponsors and Collaborators

• Tesaro, Inc.

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Jan 15, 2018
• Statistical Analysis Plan - Mar 31, 2020

More Information

Publications

None provided.

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT03359850
• Other Study ID Numbers: 213354; 3000-01-003
• First Posted: Dec 2, 2017
• Last Update Posted: May 28, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Ovarian Neoplasms; Liver Diseases; Niraparib

Study Results

Participant Flow

Recruitment Details	This study evaluated pharmacokinetics and safety of niraparib in participants with advanced solid tumors and with either normal hepatic function or moderate hepatic impairment.
Pre-assignment Detail	This is a 2 period study including pharmacokinetic (PK) phase and extension (Ext.) phase. A total of 17 participants were enrolled in the study and received study treatment, niraparib.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Period Title: PK Phase (Up to Day 8)
STARTED	9	8
COMPLETED	8	7
NOT COMPLETED	1	1
Period Title: PK Phase (Up to Day 8)
STARTED	8	7
COMPLETED	0	1
NOT COMPLETED	8	6

Baseline Characteristics

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function	Total
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	Total of all reporting groups
Overall Participants	9	8	17
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.8 (6.69)	63.6 (7.71)	64.2 (6.98)
Sex: Female, Male (Count of Participants)
Female	2 22.2%	4 50%	6 35.3%
Male	7 77.8%	4 50%	11 64.7%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	1 11.1%	0 0%	1 5.9%
White	8 88.9%	8 100%	16 94.1%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Niraparib and Its Major Metabolite (M1) During PK Phase
Description	Blood samples were collected at indicated time points to evaluate AUC (last) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1

Outcome Measure Data

Analysis Population Description

PK population consisted of all participants who have received niraparib and have sufficient evaluable samples

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	8
Niraparib	18500 (37.7)	26800 (49.6)
M1	19000 (27.5)	12400 (55.0)

2. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase
Description	Blood samples were collected at indicated time points to evaluate AUC (0-infinity) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1

Outcome Measure Data

Analysis Population Description

PK population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	7
Niraparib, n= 9, 7	19700 (38.7)	30800 (54.3)
M1, n=9, 3	20700 (29.8)	21500 (25.4)

3. Primary Outcome

Title	Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase
Description	Blood samples were collected at indicated time points to evaluate Cmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	8
Niraparib	594 (45.6)	553 (47.4)
M1	398 (17.6)	151 (89.3)

4. Primary Outcome

Title	Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase
Description	Blood samples were collected at indicated time points to evaluate tmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	8
Niraparib	4.00	4.09
M1	6.00	17.73

5. Primary Outcome

Title	Terminal Half-life (t½) of Niraparib and M1 During PK Phase
Description	Blood samples were collected at indicated time points to evaluate t1/2 of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1

Outcome Measure Data

Analysis Population Description

PK population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	7
Niraparib, n=9, 7	43.9 (11.5)	54.8 (25.8)
M1, n=9, 3	47.9 (16.6)	43.7 (20.7)

6. Primary Outcome

Title	Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase
Description	CL/F is calculated as Dose/(AUC 0-inf). Blood samples were collected at indicated time points to evaluate CL/F of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. Not applicable (NA) indicates that CL/F could not be measured for M1 since the dose of metabolite is unknown and only known dose is that of parent niraparib.
Time Frame	Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1

Outcome Measure Data

Analysis Population Description

PK population. Only those participants with data available at specified data points were analyzed. CL/F could not be measured for M1 since the dose of metabolite is unknown and only known dose is that of parent niraparib.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	7
Niraparib	15.2 (38.7)	9.74 (54.3)
M1	NA (NA)	NA (NA)

7. Other Pre-specified Outcome

Title	Plasma Protein Unbound Fraction (Fu) of Niraparib and M1 During PK Phase
Description	Unbound fraction is the unbound concentration of niraparib and M1 in plasma divided by total concentration. This analysis was planned but not performed due to insufficient participants with data
Time Frame	Pre-dose, 3 hours and 168 hours post dose Day 1

Outcome Measure Data

Analysis Population Description

PK population.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	0	0

8. Other Pre-specified Outcome

Title	Clearance of Unbound Niraparib and M1 (CLfu/F) During PK Phase
Description	CLfu/F is the clearance for unbound niraparib and M1. This analysis was planned but not performed due to insufficient participants with data
Time Frame	Pre-dose, 3 hours and 168 hours post dose Day 1

Outcome Measure Data

Analysis Population Description

PK population.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	0	0

9. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAE) Including Non-serious Adverse Events (Non-SAEs), Serious Adverse Events (SAEs) and Discontinuations Due to AEs During PK Phase
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as 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 disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are 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.
Time Frame	Up to Day 8

Outcome Measure Data

Analysis Population Description

Safety Population for PK phase consisted of all participants who received atleast one dose of the investigational drug niraparib during the PK phase.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	8
Any Non -SAEs	5 55.6%	3 37.5%
Any SAE	1 11.1%	0 0%
Any Discontinuations due to AE	1 11.1%	0 0%

10. Secondary Outcome

Title	Change From Baseline in Hemoglobin (Hb) During PK Phase
Description	Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline and at Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified data points were analyzed.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	8
Mean (Standard Deviation) [Grams per liter]	-0.5 (7.82)	0.6 (7.65)

11. Secondary Outcome

Title	Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase
Description	Blood samples were collected to analyze hematology parameters:Leukocyte, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified data points were analyzed.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	8
Lymphocytes	0.2 (0.38)	-0.1 (0.15)
Monocytes	0.1 (0.32)	-0.1 (0.24)
Neutrophils	-0.5 (2.13)	-0.7 (1.89)
Platelets	-18.4 (95.41)	-23.4 (60.31)
Leukocyte	-0.2 (2.04)	-0.8 (2.16)

12. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase
Description	Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified data points were analyzed.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	8
Protein	-1.0 (4.24)	-3.5 (5.55)
Albumin	-0.9 (2.03)	-2.3 (3.45)

13. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase
Description	Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified data points were analyzed.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	8
Alkaline phosphatase	26.3 (50.67)	-32.6 (219.03)
AST	34.6 (94.42)	-6.4 (43.81)
ALT	24.3 (60.82)	-4.4 (10.39)
LDH	36.0 (134.66)	-58.5 (137.97)

14. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter of Amylase During PK Phase
Description	Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified data points were analyzed.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	7
Mean (Standard Deviation) [Units per Liter]	74.4 (206.90)	0.3 (22.92)

15. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase
Description	Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified data points were analyzed.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	8
Bilirubin	0.6 (3.41)	8.3 (9.47)
Creatinine	-1.9 (10.87)	-0.7 (17.19)

16. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase
Description	Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	8
Glucose, n=8, 8	-0.8 (1.14)	-0.5 (1.61)
Calcium, n=8, 8	0.0 (0.17)	-0.1 (0.15)
Chloride, n=8, 8	1.8 (2.25)	-0.3 (1.83)
Phosphate, n=8, 8	0.1 (0.16)	-0.1 (0.14)
Potassium, n=8, 8	-0.2 (0.26)	-0.2 (0.74)
Sodium, n=8, 8	1.6 (2.26)	-0.5 (2.78)
BUN, n=8, 8	-0.4 (1.66)	-0.1 (0.97)
Magnesium, n=8, 7	-0.0 (0.09)	0.0 (0.09)

17. Secondary Outcome

Title	Change From Baseline in Weight During PK Phase
Description	Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline, Day 2 and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	8
Day 2, n=8, 6	-0.0 (0.58)	0.8 (0.87)
Day 8, n=9, 8	-0.0 (1.14)	0.3 (1.30)

18. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase
Description	Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline, Day 2 and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	8
SBP, Day 2, n=9, 7	5.9 (10.79)	5.7 (10.23)
SBP, Day 8, n=9, 8	0.9 (18.58)	0.3 (9.69)
DBP, Day 2, n=9, 7	3.6 (8.38)	2.7 (3.15)
DBP, Day 8, n=9, 8	2.4 (9.08)	-0.1 (11.18)

19. Secondary Outcome

Title	Change From Baseline in Pulse Rate During PK Phase
Description	Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline, Day 2 and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	8
Day 2, n=9, 7	8.9 (11.30)	1.3 (10.58)
Day 8, n=9, 8	2.8 (11.91)	-2.3 (7.85)

20. Secondary Outcome

Title	Change From Baseline in Body Temperature During PK Phase
Description	Vital sign including body temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Time Frame	Baseline, Day 2 and Day 8

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	9	8
Day 2, n=9, 7	-0.0 (0.39)	0.1 (0.24)
Day 8, n=9, 8	0.1 (0.33)	0.1 (0.47)

21. Secondary Outcome

Title	Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as 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 disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are 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.
Time Frame	Up to 28 months

Outcome Measure Data

Analysis Population Description

Safety Population for extension phase consisted of all participants who received atleast one dose of the investigational drug niraparib during the extension phase.

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	7
Any Non-SAEs	8 88.9%	7 87.5%
Any SAE	3 33.3%	2 25%
Any Discontinuations due to AE	0 0%	1 12.5%

22. Secondary Outcome

Title	Change From Baseline in Hb During Extension Phase
Description	Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	5
Cycle 1 Day 8, n=8, 5	4.3 (5.78)	1.0 (8.89)
Cycle 1 Day 15, n=8, 4	-0.5 (6.32)	-8.3 (15.73)
Cycle 1 Day 21, n=7, 4	-2.6 (12.91)	-22.3 (17.19)
Cycle 2 Day 1, n=6, 2	-8.0 (14.93)	-15.0 (1.41)
Cycle 3 Day 1, n=3, 1	-16.7 (12.10)	-10.0 (NA)
Cycle 4 Day 1, n=3, 0	-10.7 (11.06)
Cycle 5 Day 1, n=3, 0	-3.7 (2.08)
Cycle 6 Day1, n=2, 0	3.0 (7.07)

23. Secondary Outcome

Title	Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase
Description	Blood samples were collected to analyze hematology parameters: Lymphocytes, Leukocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	8	5
Lymphocytes, Cycle 1 Day 8, n=7, 5	-0.2 (0.36)	-0.1 (0.22)
Lymphocytes, Cycle 1 Day 15, n=8, 4	-0.1 (0.37)	-0.0 (0.48)
Lymphocytes, Cycle 1 Day 21, n=7, 4	-0.1 (0.25)	-0.2 (0.20)
Lymphocytes, Cycle 2 Day 1, n=6, 2	-0.1 (0.33)	0.1 (0.04)
Lymphocytes, Cycle 3 Day 1, n=3, 1	-0.3 (0.24)	0.2 (NA)
Lymphocytes, Cycle 4 Day 1, n=3, 0	0.0 (0.33)
Lymphocytes, Cycle 5 Day 1, n=3, 0	0.3 (0.30)
Lymphocytes, Cycle 6 Day1, n=2, 0	-0.0 (0.54)
Monocytes, Cycle 1 Day 8, n=7, 5	-0.1 (0.20)	0.0 (0.11)
Monocytes, Cycle 1 Day 15, n=8, 4	-0.2 (0.28)	-0.1 (0.22)
Monocytes, Cycle 1 Day 21, n=7, 4	-0.2 (0.20)	-0.1 (0.40)
Monocytes, Cycle 2 Day 1, n=6, 2	-0.1 (0.14)	-0.1 (0.16)
Monocytes, Cycle 3 Day 1, n=3, 1	-0.2 (0.06)	0.0 (NA)
Monocytes, Cycle 4 Day 1, n=3, 0	-0.0 (0.09)
Monocytes, Cycle 5 Day 1, n=3, 0	-0.1 (0.10)
Monocytes, Cycle 6 Day1, n=2, 0	-0.1 (0.16)
Neutrophils, Cycle 1 Day 8, n=7, 5	0.4 (0.87)	0.4 (0.44)
Neutrophils, Cycle 1 Day 15, n=8, 4	0.3 (1.01)	0.5 (0.73)
Neutrophils, Cycle 1 Day 21, n=7, 4	-0.6 (1.92)	-0.2 (0.81)
Neutrophils, Cycle 2 Day 1, n=6, 2	0.6 (2.03)	-1.8 (1.94)
Neutrophils, Cycle 3 Day 1, n=3, 1	-0.0 (1.70)	-0.5 (NA)
Neutrophils, Cycle 4 Day 1, n=3, 0	-0.4 (0.51)
Neutrophils, Cycle 5 Day 1, n=3, 0	0.5 (0.27)
Neutrophils, Cycle 6 Day1, n=2, 0	-0.1 (0.78)
Platelets, Cycle 1 Day 8, n=8, 5	12.0 (21.75)	-0.8 (21.32)
Platelets, Cycle 1 Day 15, n=8, 4	-58.1 (118.98)	-8.3 (63.33)
Platelets, Cycle 1 Day 21, n=7, 4	-81.9 (113.91)	-19.3 (57.70)
Platelets, Cycle 2 Day 1, n=6, 2	55.3 (128.24)	-102.5 (130.81)
Platelets, Cycle 3 Day 1, n=3, 1	-46.3 (36.46)	59.0 (NA)
Platelets, Cycle 4 Day 1, n=3, 0	34.0 (43.92)
Platelets, Cycle 5 Day 1, n=3, 0	45.7 (22.68)
Platelets, Cycle 6 Day1, n=2, 0	34.0 (42.43)
Leukocytes, Cycle 1 Day 8, n=8, 5	0.4 (1.76)	0.3 (0.40)
Leukocytes, Cycle 1 Day 15, n=8, 4	-0.1 (1.25)	0.4 (1.28)
Leukocytes, Cycle 1 Day 21, n=7, 4	-1.0 (2.05)	-0.5 (1.36)
Leukocytes, Cycle 2 Day 1, n=6, 2	0.5 (1.96)	-1.9 (1.91)
Leukocytes, Cycle 3 Day 1, n=3, 1	-0.5 (1.67)	-0.2 (NA)
Leukocytes, Cycle 4 Day 1, n=3, 0	-0.4 (0.76)
Leukocytes, Cycle 5 Day 1, n=3, 0	0.9 (0.31)
Leukocytes, Cycle 6 Day1, n=2, 0	-0.3 (1.48)

24. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase
Description	Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	6	2
Protein, Cycle 2 Day 1, n=6, 2	-1.0 (6.96)	-2.0 (0.00)
Protein, Cycle 3 Day 1, n=3, 1	-2.0 (3.46)	-5.0 (NA)
Protein, Cycle 4 Day 1, n=3, 0	1.0 (3.61)
Protein, Cycle 5 Day 1, n=3, 0	4.0 (2.65)
Protein, Cycle 6 Day1, n=2, 0	0.0 (2.83)
Albumin, Cycle 2 Day 1, n=6, 2	0.3 (4.37)	-1.0 (0.00)
Albumin, Cycle 3 Day 1, n=3, 1	1.0 (2.65)	-1.0 (NA)
Albumin, Cycle 4 Day 1, n=3, 0	2.7 (3.21)
Albumin, Cycle 5 Day 1, n=3, 0	4.7 (2.52)
Albumin, Cycle 6 Day1, n=2, 0	17.0 (16.97)

25. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase
Description	Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	6	2
Alkaline Phosphatase, Cycle 2 Day 1, n=6, 2	23.3 (17.43)	-53.5 (221.32)
Alkaline Phosphatase, Cycle 3 Day 1, n=3, 1	19.7 (5.03)	57.0 (NA)
Alkaline Phosphatase, Cycle 4 Day 1, n=3, 0	20.0 (10.54)
Alkaline Phosphatase, Cycle 5 Day 1, n=3, 0	12.0 (14.80)
Alkaline Phosphatase, Cycle 6 Day1, n=2, 0	1.5 (16.26)
ALT, Cycle 2 Day 1, n=6, 2	11.8 (19.77)	-6.5 (20.51)
ALT, Cycle 3 Day 1, n=3, 1	4.7 (6.11)	4.0 (NA)
ALT, Cycle 4 Day 1, n=3, 0	2.0 (5.00)
ALT, Cycle 5 Day 1, n=3, 0	5.3 (7.02)
ALT, Cycle 6 Day1, n=2, 0	2.0 (4.24)
AST, Cycle 2 Day 1, n=6, 2	4.8 (5.81)	-25.0 (38.18)
AST, Cycle 3 Day 1, n=3, 1	2.0 (2.65)	4.0 (NA)
AST, Cycle 4 Day 1, n=3, 0	4.3 (2.31)
AST, Cycle 5 Day 1, n=3, 0	5.3 (2.52)
AST, Cycle 6 Day1, n=2, 0	5.5 (4.95)
LDH, Cycle 2 Day 1, n=3, 2	11.7 (37.53)	-625.0 (847.11)
LDH, Cycle 3 Day 1, n=3, 1	6.7 (17.56)	-9.0 (NA)
LDH, Cycle 4 Day 1, n=3, 0	-11.7 (41.77)
LDH, Cycle 5 Day 1, n=3, 0	-5.3 (21.46)
LDH, Cycle 6 Day1, n=2, 0	19.0 (35.36)

26. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase
Description	Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	4	2
Cycle 2 Day 1, n=4, 2	-1.0 (16.39)	-2.5 (6.36)
Cycle 3 Day 1, n=3, 1	-7.0 (14.18)	-4.0 (NA)
Cycle 4 Day 1, n=3, 0	-2.3 (16.77)
Cycle 5 Day 1, n=3, 0	3.0 (5.57)
Cycle 6 Day1, n=2, 0	-2.5 (31.82)

27. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase
Description	Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	6	2
Bilirubin, Cycle 2 Day 1, n=6, 2	0.9 (1.79)	-6.0 (8.46)
Bilirubin, Cycle 3 Day 1, n=3, 1	0.6 (2.61)	1.7 (NA)
Bilirubin, Cycle 4 Day 1, n=3, 0	0.6 (0.99)
Bilirubin, Cycle 5 Day 1, n=3, 0	2.9 (0.99)
Bilirubin, Cycle 6 Day1, n=2, 0	-0.9 (1.21)
Creatinine, Cycle 2 Day 1, n=6, 2	7.5 (17.93)	18.1 (3.13)
Creatinine, Cycle 3 Day 1, n=3, 1	13.0 (5.03)	0.0 (NA)
Creatinine, Cycle 4 Day 1, n=3, 0	0.9 (9.56)
Creatinine, Cycle 5 Day 1, n=3, 0	5.6 (2.84)
Creatinine, Cycle 6 Day1, n=2, 0	5.7 (5.63)

28. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase
Description	Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	6	2
Glucose, Cycle 2 Day 1, n=6, 2	-0.0 (1.45)	1.6 (0.47)
Glucose, Cycle 3 Day 1, n=3, 1	0.7 (1.50)	-2.3 (NA)
Glucose, Cycle 4 Day 1, n=3, 0	-0.4 (0.95)
Glucose, Cycle 5 Day 1, n=3, 0	-0.7 (0.90)
Glucose, Cycle 6 Day1, n=2, 0	-0.8 (0.90)
Calcium, Cycle 2 Day 1, n=6, 2	-0.0 (0.16)	0.0 (0.14)
Calcium, Cycle 3 Day 1, n=3, 1	0.0 (0.06)	0.0 (NA)
Calcium, Cycle 4 Day 1, n=3, 0	0.0 (0.00)
Calcium, Cycle 5 Day 1, n=3, 0	0.1 (0.10)
Calcium, Cycle 6 Day1, n=2, 0	-0.0 (0.02)
Chloride, Cycle 2 Day 1, n=6, 2	-1.7 (2.25)	-3.5 (2.12)
Chloride, Cycle 3 Day 1, n=3, 1	-2.0 (3.61)	0.0 (NA)
Chloride, Cycle 4 Day 1, n=3, 0	-0.7 (1.53)
Chloride, Cycle 5 Day 1, n=3, 0	-1.7 (1.15)
Chloride, Cycle 6 Day1, n=2, 0	-2.5 (2.12)
Phosphate, Cycle 2 Day 1, n=5, 2	-0.2 (0.34)	0.3 (0.02)
Phosphate, Cycle 3 Day 1, n=3, 1	0.0 (0.18)	-0.1 (NA)
Phosphate, Cycle 4 Day 1, n=3, 0	-0.1 (0.26)
Phosphate, Cycle 5 Day 1, n=3, 0	0.0 (0.43)
Phosphate, Cycle 6 Day1, n=2, 0	0.0 (0.30)
Potassium, Cycle 2 Day 1, n=6, 2	-0.2 (0.12)	0.1 (0.21)
Potassium, Cycle 3 Day 1, n=3, 1	0.1 (0.30)	0.4 (NA)
Potassium, Cycle 4 Day 1, n=3, 0	0.0 (0.20)
Potassium, Cycle 5 Day 1, n=3, 0	0.1 (0.38)
Potassium, Cycle 6 Day1, n=2, 0	0.1 (0.21)
Sodium, Cycle 2 Day 1, n=6, 2	-1.8 (1.17)	-1.5 (2.12)
Sodium, Cycle 3 Day 1, n=3, 1	-3.0 (1.73)	1.0 (NA)
Sodium, Cycle 4 Day 1, n=3, 0	-1.0 (1.73)
Sodium, Cycle 5 Day 1, n=3, 0	-1.7 (0.58)
Sodium, Cycle 6 Day1, n=2, 0	-1.5 (2.12)
BUN, Cycle 2 Day 1, n=6, 2	0.3 (2.15)	1.8 (0.50)
BUN, Cycle 3 Day 1, n=3, 1	0.7 (2.14)	1.4 (NA)
BUN, Cycle 4 Day 1, n=3, 0	-1.0 (0.90)
BUN, Cycle 5 Day 1, n=3, 0	-0.5 (1.25)
BUN, Cycle 6 Day1, n=2, 0	-0.5 (0.76)
Magnesium, Cycle 2 Day 1, n=5, 2	-0.0 (0.09)	0.0 (0.00)
Magnesium, Cycle 3 Day 1, n=3, 1	-0.0 (0.04)	0.1 (NA)
Magnesium, Cycle 4 Day 1, n=2, 0	0.0 (0.00)
Magnesium, Cycle 5 Day 1, n=2, 0	0.1 (0.00)
Magnesium, Cycle 6 Day1, n=1, 0	0.0 (NA)

29. Secondary Outcome

Title	Change From Baseline in Weight During Extension Phase
Description	Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	6	2
Cycle 2 Day 1, n=6, 2	-1.6 (1.74)	-4.6 (4.31)
Cycle 3 Day 1, n=3, 1	-0.3 (1.00)	-4.5 (NA)
Cycle 4 Day 1, n=3, 0	-2.3 (0.85)
Cycle 5 Day 1, n=3, 0	-3.3 (2.91)
Cycle 6 Day1, n=2, 0	-0.4 (0.92)

30. Secondary Outcome

Title	Change From Baseline in SBP and DBP During Extension Phase
Description	Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	6	2
DBP, Cycle 2 Day 1, n=6, 2	-0.2 (3.19)	-12.0 (12.73)
DBP, Cycle 3 Day 1, n=3, 1	8.7 (9.81)	-9.0 (NA)
DBP, Cycle 4 Day 1, n=3, 0	-0.3 (3.06)
DBP, Cycle 5 Day 1, n=3, 0	12.3 (6.51)
DBP, Cycle 6 Day1, n=2, 0	6.5 (4.95)
SBP, Cycle 2 Day 1, n=6, 2	-1.2 (12.89)	-2.5 (23.33)
SBP, Cycle 3 Day 1, n=3, 1	6.7 (10.97)	-6.0 (NA)
SBP, Cycle 4 Day 1, n=3, 0	-2.3 (7.57)
SBP, Cycle 5 Day 1, n=3, 0	5.7 (10.02)
SBP, Cycle 6 Day1, n=2, 0	13.0 (1.41)

31. Secondary Outcome

Title	Change From Baseline in Pulse Rate During Extension Phase
Description	Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	6	2
Cycle 2 Day 1, n=6, 2	17.2 (10.15)	9.0 (5.66)
Cycle 3 Day 1, n=3, 1	23.0 (20.78)	4.0 (NA)
Cycle 4 Day 1, n=3, 0	15.3 (8.08)
Cycle 5 Day 1, n=3, 0	9.3 (11.55)
Cycle 6 Day1, n=2, 0	16.5 (9.19)

32. Secondary Outcome

Title	Change From Baseline in Temperature During Extension Phase
Description	Vital sign including temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time Frame	Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Participants With Normal Hepatic Function	Participants With Impaired Hepatic Function
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).	All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
Measure Participants	6	2
Cycle 2 Day 1, n=6, 2	-0.3 (0.77)	0.1 (0.07)
Cycle 3 Day 1, n=3, 1	-0.1 (0.26)	0.0 (NA)
Cycle 4 Day 1, n=3, 0	-0.0 (0.38)
Cycle 5 Day 1, n=3, 0	-0.1 (0.21)
Cycle 6 Day1, n=2, 0	-0.3 (0.21)

Adverse Events

Time Frame	All cause mortality, non-SAEs and SAEs were reported from start of study treatment and up to Day 8 in PK Phase and up to 28 months in Extension Phase.
Adverse Event Reporting Description	All cause mortality, non-SAEs and SAEs were reported for Safety Population consisting of all participants who received atleast 1 dose of the investigational drug, niraparib. The results are presented based on final analysis up to 28 months.
Arm/Group Title	Participants With Normal Hepatic Function-PK Phase		Participants With Impaired Hepatic Function-PK Phase		Participants With Normal Hepatic Function-Extension Phase		Participants With Impaired Hepatic Function-Extension Phase
Arm/Group Description	All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).		All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).		All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).		All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days).
All Cause Mortality
	Participants With Normal Hepatic Function-PK Phase		Participants With Impaired Hepatic Function-PK Phase		Participants With Normal Hepatic Function-Extension Phase		Participants With Impaired Hepatic Function-Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/8 (0%)		2/8 (25%)		4/7 (57.1%)
Serious Adverse Events
	Participants With Normal Hepatic Function-PK Phase		Participants With Impaired Hepatic Function-PK Phase		Participants With Normal Hepatic Function-Extension Phase		Participants With Impaired Hepatic Function-Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		0/8 (0%)		3/8 (37.5%)		2/7 (28.6%)
Gastrointestinal disorders
Abdominal pain	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Intestinal obstruction	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
General disorders
Pyrexia	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Infections and infestations
Influenza	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Pneumonia	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Sepsis	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Pulmonary hypertension	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Participants With Normal Hepatic Function-PK Phase		Participants With Impaired Hepatic Function-PK Phase		Participants With Normal Hepatic Function-Extension Phase		Participants With Impaired Hepatic Function-Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)		3/8 (37.5%)		8/8 (100%)		7/7 (100%)
Blood and lymphatic system disorders
Lymphopenia	0/9 (0%)		1/8 (12.5%)		0/8 (0%)		0/7 (0%)
Anaemia	0/9 (0%)		0/8 (0%)		3/8 (37.5%)		5/7 (71.4%)
Thrombocytopenia	0/9 (0%)		0/8 (0%)		2/8 (25%)		5/7 (71.4%)
Neutropenia	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Cardiac disorders
Sinus tachycardia	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Supraventricular tachycardia	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Ventricular tachycardia	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Ear and labyrinth disorders
Hypoacusis	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Gastrointestinal disorders
Nausea	1/9 (11.1%)		1/8 (12.5%)		4/8 (50%)		1/7 (14.3%)
Abdominal distension	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Vomiting	1/9 (11.1%)		0/8 (0%)		1/8 (12.5%)		2/7 (28.6%)
Constipation	0/9 (0%)		0/8 (0%)		4/8 (50%)		3/7 (42.9%)
Abdominal pain	0/9 (0%)		0/8 (0%)		2/8 (25%)		3/7 (42.9%)
Ascites	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Diarrhoea	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Dry mouth	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Intestinal obstruction	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
General disorders
Fatigue	0/9 (0%)		1/8 (12.5%)		7/8 (87.5%)		5/7 (71.4%)
Oedema peripheral	0/9 (0%)		0/8 (0%)		0/8 (0%)		2/7 (28.6%)
Asthenia	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Gait disturbance	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Pain	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Pyrexia	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/9 (0%)		2/8 (25%)		0/8 (0%)		2/7 (28.6%)
Jaundice	0/9 (0%)		0/8 (0%)		0/8 (0%)		2/7 (28.6%)
Infections and infestations
Urinary tract infection	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		1/7 (14.3%)
Pneumonia	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Upper respiratory tract infection	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Sepsis	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Influenza	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Injury, poisoning and procedural complications
Fall	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Investigations
Alanine aminotransferase increased	1/9 (11.1%)		1/8 (12.5%)		0/8 (0%)		1/7 (14.3%)
Aspartate aminotransferase increased	1/9 (11.1%)		1/8 (12.5%)		0/8 (0%)		2/7 (28.6%)
Amylase increased	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Lipase increased	1/9 (11.1%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Blood creatinine increased	0/9 (0%)		0/8 (0%)		2/8 (25%)		1/7 (14.3%)
Platelet count decreased	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		1/7 (14.3%)
Weight decreased	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		1/7 (14.3%)
Blood bilirubin increased	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Metabolism and nutrition disorders
Decreased appetite	0/9 (0%)		1/8 (12.5%)		2/8 (25%)		3/7 (42.9%)
Hyponatraemia	0/9 (0%)		1/8 (12.5%)		1/8 (12.5%)		1/7 (14.3%)
Hypokalaemia	0/9 (0%)		0/8 (0%)		0/8 (0%)		2/7 (28.6%)
Hypophosphataemia	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/9 (11.1%)		0/8 (0%)		2/8 (25%)		0/7 (0%)
Musculoskeletal pain	0/9 (0%)		0/8 (0%)		2/8 (25%)		0/7 (0%)
Myalgia	0/9 (0%)		0/8 (0%)		2/8 (25%)		0/7 (0%)
Arthralgia	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Muscle tightness	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Musculoskeletal discomfort	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Nervous system disorders
Neuropathy peripheral	0/9 (0%)		1/8 (12.5%)		0/8 (0%)		0/7 (0%)
Taste disorder	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Dizziness	0/9 (0%)		0/8 (0%)		2/8 (25%)		0/7 (0%)
Headache	0/9 (0%)		0/8 (0%)		2/8 (25%)		0/7 (0%)
Dysgeusia	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Hepatic encephalopathy	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Paraesthesia	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Tremor	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Psychiatric disorders
Insomnia	0/9 (0%)		0/8 (0%)		3/8 (37.5%)		0/7 (0%)
Confusional state	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		1/7 (14.3%)
Renal and urinary disorders
Acute kidney injury	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Haematuria	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Reproductive system and breast disorders
Vaginal haemorrhage	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Dyspnoea	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Haemoptysis	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Nasal congestion	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Oropharyngeal pain	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Paranasal sinus discomfort	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Pulmonary embolism	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Acute respiratory failure	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Pulmonary hypertension	1/9 (11.1%)		0/8 (0%)		0/8 (0%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Pruritus	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Skin mass	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)
Skin ulcer	0/9 (0%)		0/8 (0%)		0/8 (0%)		1/7 (14.3%)
Vascular disorders
Hypertension	0/9 (0%)		0/8 (0%)		1/8 (12.5%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.