Hepatic Impairment, Neoplasms, Ovarian Neoplasms, Solid Tumor
Conditions
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.
Interventions
DRUGNiraparib
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.
Sponsors
Tesaro, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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. 6. Male patient agrees to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment.. 7. Patient is able to understand the study procedures and agrees to participate in the study by providing written informed consent. Patients with normal hepatic function (Group 1): Patients screened for the normal hepatic function group must meet the following additional criteria to be eligible for enrollment: 1. Patient has no history of hepatic impairment. 2. Patient has liver function test (LFT) results within normal range: * Total bilirubin ≤ ULN * Aspartate aminotransferase (AST) ≤ ULN. * INR ≤1.5 X ULN unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants. 3. Patient has adequate hematologic and renal function as defined below: * Absolute neutrophil count ≥1500/µL * Platelets ≥100,000/µL * Hemoglobin ≥9 g/dL * Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation. Patients with moderate hepatic impairment (Group 2): Patients screened for the moderate hepatic impairment group must meet the following additional criteria to be eligible for enrollment: 1. Patient has stable, moderate hepatic impairment, defined as: * BILI: \>1.5 × to 3 × ULN, for at least 2 weeks prior to Day 1 * AST: Any value * INR less than 1.8 unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants. 2. Patient has hematologic and renal function as defined below: * Absolute neutrophil count ≥1000/µL * Platelets ≥75,000/µL * Hemoglobin ≥8 g/dL * Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation. 3. Patient's hepatic disease is deemed stable by the Investigator Criteria for Exclusion: Patients will not be eligible for study entry if any of the following criteria are met: All patients: 1. Patient has undergone palliative radiotherapy within 1 week of study drug administration, encompassing \>20% of the bone marrow. 2. Patient is starting chemotherapy within 3 weeks of study drug administration. 3. Patient has a known hypersensitivity to the components of niraparib or excipients 4. Patients who received colony-stimulating factors within 2 weeks prior to the first dose of study treatment are not eligible. 5. Patient has persistent chemotherapy associated Grade 2 or greater toxicity except for neuropathy, alopecia or fatigue. 6. Patient has symptomatic uncontrolled brain or leptomeningeal metastases. 7. Patient has undergone major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery. 8. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder (other than hepatic impairment) or active, uncontrolled infection. 9. Patient has received a transfusion (platelets or red blood cells) within 3 weeks of receiving niraparib. 10. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment or for 3 months after the last dose of study treatment. 11. Patient has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). NOTE:
Exclusion criteria
12-16 apply patients participating in the PK phase of the study. 12. Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the time of the last PK blood draw, any of the following cytochrome (CYP) 1A2 substrates: alosetron, duloxetine, melatonin, ramelteon, tacrine, tizanidine, and theophylline. 13. Patient is unable to refrain from any intake of grapefruit or grapefruit juice within 4 days of the first administration of niraparib until the final PK sample collection. 14. Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the last PK blood draw, any of the following P-glycoprotein (P-gp) inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor and verapamil. 15. Patient is taking proton pump inhibitors, antacids, or histamine 2 (H2) blockers within 48 hours prior to niraparib administration, and/or within 6 hours after niraparib administration. 16. Patient has esophagogastrointestinal disease or resection that is likely to interfere with the absorption of niraparib. Patients with moderate hepatic impairment (Group 2): Patients screened for the moderate hepatic impairment group who meet any of the following additional criteria will be excluded from the study: 1. Patient has hepatic encephalopathy, severe portal hypertension and/or porto-systemic shunt. 2. Patient has fluctuating or rapidly deteriorating hepatic function as determined by the investigator within the screening period. 3. Patient has acute liver disease caused by drug toxicity or by an infection. 4. Patient has biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver. 5. Patient has esophageal variceal bleeding within the past 2 months. 6. Patient is receiving anticoagulant therapy with warfarin or related coumarins. 7. Patient has a history of hepatic transplant, systemic lupus erythematosus, or hepatic coma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Participants With Normal Hepatic Function 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). | 9 |
| Participants With Impaired Hepatic Function 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). | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Phase (Up to 28 Months) | Death | 2 | 4 |
| Extension Phase (Up to 28 Months) | Disease Progression | 5 | 0 |
| Extension Phase (Up to 28 Months) | Withdrawal by Subject | 1 | 2 |
| PK Phase (Up to Day 8) | Adverse Event | 1 | 0 |
| PK Phase (Up to Day 8) | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Participants With Impaired Hepatic Function | Total | Participants With Normal Hepatic Function |
|---|---|---|---|
| Age, Continuous | 63.6 Years STANDARD_DEVIATION 7.71 | 64.2 Years STANDARD_DEVIATION 6.98 | 64.8 Years STANDARD_DEVIATION 6.69 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 | 2 / 8 | 4 / 7 |
| other Total, other adverse events | 5 / 9 | 3 / 8 | 8 / 8 | 7 / 7 |
| serious Total, serious adverse events | 1 / 9 | 0 / 8 | 3 / 8 | 2 / 7 |
Outcome results
Primary
Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase | Niraparib | 15.2 Liters per hour | Geometric Coefficient of Variation 38.7 |
| Participants With Normal Hepatic Function | Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase | M1 | NA Liters per hour | — |
| Participants With Impaired Hepatic Function | Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase | Niraparib | 9.74 Liters per hour | Geometric Coefficient of Variation 54.3 |
| Participants With Impaired Hepatic Function | Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase | M1 | NA Liters per hour | — |
Primary
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase
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
Population: PK population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase | Niraparib, n= 9, 7 | 19700 Hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 38.7 |
| Participants With Normal Hepatic Function | Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase | M1, n=9, 3 | 20700 Hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 29.8 |
| Participants With Impaired Hepatic Function | Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase | Niraparib, n= 9, 7 | 30800 Hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 54.3 |
| Participants With Impaired Hepatic Function | Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase | M1, n=9, 3 | 21500 Hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 25.4 |
Primary
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
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
Population: PK population consisted of all participants who have received niraparib and have sufficient evaluable samples
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | 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 | Niraparib | 18500 Hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 37.7 |
| Participants With Normal Hepatic Function | 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 | M1 | 19000 Hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 27.5 |
| Participants With Impaired Hepatic Function | 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 | Niraparib | 26800 Hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 49.6 |
| Participants With Impaired Hepatic Function | 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 | M1 | 12400 Hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 55 |
Primary
Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase
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
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase | Niraparib | 594 Nanogram per milliliter | Geometric Coefficient of Variation 45.6 |
| Participants With Normal Hepatic Function | Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase | M1 | 398 Nanogram per milliliter | Geometric Coefficient of Variation 17.6 |
| Participants With Impaired Hepatic Function | Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase | Niraparib | 553 Nanogram per milliliter | Geometric Coefficient of Variation 47.4 |
| Participants With Impaired Hepatic Function | Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase | M1 | 151 Nanogram per milliliter | Geometric Coefficient of Variation 89.3 |
Primary
Terminal Half-life (t½) of Niraparib and M1 During PK Phase
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
Population: PK population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Terminal Half-life (t½) of Niraparib and M1 During PK Phase | Niraparib, n=9, 7 | 43.9 Hour | Geometric Coefficient of Variation 11.5 |
| Participants With Normal Hepatic Function | Terminal Half-life (t½) of Niraparib and M1 During PK Phase | M1, n=9, 3 | 47.9 Hour | Geometric Coefficient of Variation 16.6 |
| Participants With Impaired Hepatic Function | Terminal Half-life (t½) of Niraparib and M1 During PK Phase | Niraparib, n=9, 7 | 54.8 Hour | Geometric Coefficient of Variation 25.8 |
| Participants With Impaired Hepatic Function | Terminal Half-life (t½) of Niraparib and M1 During PK Phase | M1, n=9, 3 | 43.7 Hour | Geometric Coefficient of Variation 20.7 |
Primary
Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase
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
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Participants With Normal Hepatic Function | Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase | M1 | 6.00 Hour |
| Participants With Normal Hepatic Function | Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase | Niraparib | 4.00 Hour |
| Participants With Impaired Hepatic Function | Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase | Niraparib | 4.09 Hour |
| Participants With Impaired Hepatic Function | Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase | M1 | 17.73 Hour |
Secondary
Change From Baseline in Body Temperature During PK Phase
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
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Body Temperature During PK Phase | Day 2, n=9, 7 | -0.0 Degrees Celsius | Standard Deviation 0.39 |
| Participants With Normal Hepatic Function | Change From Baseline in Body Temperature During PK Phase | Day 8, n=9, 8 | 0.1 Degrees Celsius | Standard Deviation 0.33 |
| Participants With Impaired Hepatic Function | Change From Baseline in Body Temperature During PK Phase | Day 2, n=9, 7 | 0.1 Degrees Celsius | Standard Deviation 0.24 |
| Participants With Impaired Hepatic Function | Change From Baseline in Body Temperature During PK Phase | Day 8, n=9, 8 | 0.1 Degrees Celsius | Standard Deviation 0.47 |
Secondary
Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase
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
Population: Safety Population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Glucose, n=8, 8 | -0.8 Millimoles per liter | Standard Deviation 1.14 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Calcium, n=8, 8 | 0.0 Millimoles per liter | Standard Deviation 0.17 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Chloride, n=8, 8 | 1.8 Millimoles per liter | Standard Deviation 2.25 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Phosphate, n=8, 8 | 0.1 Millimoles per liter | Standard Deviation 0.16 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Potassium, n=8, 8 | -0.2 Millimoles per liter | Standard Deviation 0.26 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Sodium, n=8, 8 | 1.6 Millimoles per liter | Standard Deviation 2.26 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | BUN, n=8, 8 | -0.4 Millimoles per liter | Standard Deviation 1.66 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Magnesium, n=8, 7 | -0.0 Millimoles per liter | Standard Deviation 0.09 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Magnesium, n=8, 7 | 0.0 Millimoles per liter | Standard Deviation 0.09 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Glucose, n=8, 8 | -0.5 Millimoles per liter | Standard Deviation 1.61 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Potassium, n=8, 8 | -0.2 Millimoles per liter | Standard Deviation 0.74 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Calcium, n=8, 8 | -0.1 Millimoles per liter | Standard Deviation 0.15 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | BUN, n=8, 8 | -0.1 Millimoles per liter | Standard Deviation 0.97 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Chloride, n=8, 8 | -0.3 Millimoles per liter | Standard Deviation 1.83 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Sodium, n=8, 8 | -0.5 Millimoles per liter | Standard Deviation 2.78 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Phosphate, n=8, 8 | -0.1 Millimoles per liter | Standard Deviation 0.14 |
Secondary
Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Magnesium, Cycle 6 Day1, n=1, 0 | 0.0 Millimoles per liter | — |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Potassium, Cycle 6 Day1, n=2, 0 | 0.1 Millimoles per liter | Standard Deviation 0.21 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Sodium, Cycle 2 Day 1, n=6, 2 | -1.8 Millimoles per liter | Standard Deviation 1.17 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Sodium, Cycle 3 Day 1, n=3, 1 | -3.0 Millimoles per liter | Standard Deviation 1.73 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Sodium, Cycle 4 Day 1, n=3, 0 | -1.0 Millimoles per liter | Standard Deviation 1.73 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Sodium, Cycle 5 Day 1, n=3, 0 | -1.7 Millimoles per liter | Standard Deviation 0.58 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Sodium, Cycle 6 Day1, n=2, 0 | -1.5 Millimoles per liter | Standard Deviation 2.12 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | BUN, Cycle 2 Day 1, n=6, 2 | 0.3 Millimoles per liter | Standard Deviation 2.15 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | BUN, Cycle 3 Day 1, n=3, 1 | 0.7 Millimoles per liter | Standard Deviation 2.14 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | BUN, Cycle 4 Day 1, n=3, 0 | -1.0 Millimoles per liter | Standard Deviation 0.9 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | BUN, Cycle 5 Day 1, n=3, 0 | -0.5 Millimoles per liter | Standard Deviation 1.25 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | BUN, Cycle 6 Day1, n=2, 0 | -0.5 Millimoles per liter | Standard Deviation 0.76 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Magnesium, Cycle 2 Day 1, n=5, 2 | -0.0 Millimoles per liter | Standard Deviation 0.09 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Magnesium, Cycle 3 Day 1, n=3, 1 | -0.0 Millimoles per liter | Standard Deviation 0.04 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Magnesium, Cycle 4 Day 1, n=2, 0 | 0.0 Millimoles per liter | Standard Deviation 0 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Magnesium, Cycle 5 Day 1, n=2, 0 | 0.1 Millimoles per liter | Standard Deviation 0 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Glucose, Cycle 2 Day 1, n=6, 2 | -0.0 Millimoles per liter | Standard Deviation 1.45 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Glucose, Cycle 3 Day 1, n=3, 1 | 0.7 Millimoles per liter | Standard Deviation 1.5 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Glucose, Cycle 4 Day 1, n=3, 0 | -0.4 Millimoles per liter | Standard Deviation 0.95 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Glucose, Cycle 5 Day 1, n=3, 0 | -0.7 Millimoles per liter | Standard Deviation 0.9 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Glucose, Cycle 6 Day1, n=2, 0 | -0.8 Millimoles per liter | Standard Deviation 0.9 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Calcium, Cycle 2 Day 1, n=6, 2 | -0.0 Millimoles per liter | Standard Deviation 0.16 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Calcium, Cycle 3 Day 1, n=3, 1 | 0.0 Millimoles per liter | Standard Deviation 0.06 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Calcium, Cycle 4 Day 1, n=3, 0 | 0.0 Millimoles per liter | Standard Deviation 0 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Calcium, Cycle 5 Day 1, n=3, 0 | 0.1 Millimoles per liter | Standard Deviation 0.1 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Calcium, Cycle 6 Day1, n=2, 0 | -0.0 Millimoles per liter | Standard Deviation 0.02 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Chloride, Cycle 2 Day 1, n=6, 2 | -1.7 Millimoles per liter | Standard Deviation 2.25 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Chloride, Cycle 3 Day 1, n=3, 1 | -2.0 Millimoles per liter | Standard Deviation 3.61 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Chloride, Cycle 4 Day 1, n=3, 0 | -0.7 Millimoles per liter | Standard Deviation 1.53 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Chloride, Cycle 5 Day 1, n=3, 0 | -1.7 Millimoles per liter | Standard Deviation 1.15 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Chloride, Cycle 6 Day1, n=2, 0 | -2.5 Millimoles per liter | Standard Deviation 2.12 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Phosphate, Cycle 2 Day 1, n=5, 2 | -0.2 Millimoles per liter | Standard Deviation 0.34 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Phosphate, Cycle 3 Day 1, n=3, 1 | 0.0 Millimoles per liter | Standard Deviation 0.18 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Phosphate, Cycle 4 Day 1, n=3, 0 | -0.1 Millimoles per liter | Standard Deviation 0.26 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Phosphate, Cycle 5 Day 1, n=3, 0 | 0.0 Millimoles per liter | Standard Deviation 0.43 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Phosphate, Cycle 6 Day1, n=2, 0 | 0.0 Millimoles per liter | Standard Deviation 0.3 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Potassium, Cycle 2 Day 1, n=6, 2 | -0.2 Millimoles per liter | Standard Deviation 0.12 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Potassium, Cycle 3 Day 1, n=3, 1 | 0.1 Millimoles per liter | Standard Deviation 0.3 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Potassium, Cycle 4 Day 1, n=3, 0 | 0.0 Millimoles per liter | Standard Deviation 0.2 |
| Participants With Normal Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Potassium, Cycle 5 Day 1, n=3, 0 | 0.1 Millimoles per liter | Standard Deviation 0.38 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Glucose, Cycle 2 Day 1, n=6, 2 | 1.6 Millimoles per liter | Standard Deviation 0.47 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Chloride, Cycle 3 Day 1, n=3, 1 | 0.0 Millimoles per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Glucose, Cycle 3 Day 1, n=3, 1 | -2.3 Millimoles per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Sodium, Cycle 2 Day 1, n=6, 2 | -1.5 Millimoles per liter | Standard Deviation 2.12 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Potassium, Cycle 2 Day 1, n=6, 2 | 0.1 Millimoles per liter | Standard Deviation 0.21 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Magnesium, Cycle 2 Day 1, n=5, 2 | 0.0 Millimoles per liter | Standard Deviation 0 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Potassium, Cycle 3 Day 1, n=3, 1 | 0.4 Millimoles per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Calcium, Cycle 2 Day 1, n=6, 2 | 0.0 Millimoles per liter | Standard Deviation 0.14 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Phosphate, Cycle 2 Day 1, n=5, 2 | 0.3 Millimoles per liter | Standard Deviation 0.02 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Calcium, Cycle 3 Day 1, n=3, 1 | 0.0 Millimoles per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Sodium, Cycle 3 Day 1, n=3, 1 | 1.0 Millimoles per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Phosphate, Cycle 3 Day 1, n=3, 1 | -0.1 Millimoles per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | BUN, Cycle 2 Day 1, n=6, 2 | 1.8 Millimoles per liter | Standard Deviation 0.5 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Magnesium, Cycle 3 Day 1, n=3, 1 | 0.1 Millimoles per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Chloride, Cycle 2 Day 1, n=6, 2 | -3.5 Millimoles per liter | Standard Deviation 2.12 |
| Participants With Impaired Hepatic Function | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | BUN, Cycle 3 Day 1, n=3, 1 | 1.4 Millimoles per liter | — |
Secondary
Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase
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
Population: Safety Population. Only those participants with data available at specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | Alkaline phosphatase | 26.3 International units per Liter | Standard Deviation 50.67 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | AST | 34.6 International units per Liter | Standard Deviation 94.42 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | ALT | 24.3 International units per Liter | Standard Deviation 60.82 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | LDH | 36.0 International units per Liter | Standard Deviation 134.66 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | LDH | -58.5 International units per Liter | Standard Deviation 137.97 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | Alkaline phosphatase | -32.6 International units per Liter | Standard Deviation 219.03 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | ALT | -4.4 International units per Liter | Standard Deviation 10.39 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | AST | -6.4 International units per Liter | Standard Deviation 43.81 |
Secondary
Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | LDH, Cycle 6 Day1, n=2, 0 | 19.0 International units per Liter | Standard Deviation 35.36 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | AST, Cycle 4 Day 1, n=3, 0 | 4.3 International units per Liter | Standard Deviation 2.31 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | AST, Cycle 5 Day 1, n=3, 0 | 5.3 International units per Liter | Standard Deviation 2.52 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | AST, Cycle 6 Day1, n=2, 0 | 5.5 International units per Liter | Standard Deviation 4.95 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | LDH, Cycle 2 Day 1, n=3, 2 | 11.7 International units per Liter | Standard Deviation 37.53 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | LDH, Cycle 3 Day 1, n=3, 1 | 6.7 International units per Liter | Standard Deviation 17.56 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | LDH, Cycle 4 Day 1, n=3, 0 | -11.7 International units per Liter | Standard Deviation 41.77 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | LDH, Cycle 5 Day 1, n=3, 0 | -5.3 International units per Liter | Standard Deviation 21.46 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | Alkaline Phosphatase, Cycle 2 Day 1, n=6, 2 | 23.3 International units per Liter | Standard Deviation 17.43 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | Alkaline Phosphatase, Cycle 3 Day 1, n=3, 1 | 19.7 International units per Liter | Standard Deviation 5.03 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | Alkaline Phosphatase, Cycle 4 Day 1, n=3, 0 | 20.0 International units per Liter | Standard Deviation 10.54 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | Alkaline Phosphatase, Cycle 5 Day 1, n=3, 0 | 12.0 International units per Liter | Standard Deviation 14.8 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | Alkaline Phosphatase, Cycle 6 Day1, n=2, 0 | 1.5 International units per Liter | Standard Deviation 16.26 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | ALT, Cycle 2 Day 1, n=6, 2 | 11.8 International units per Liter | Standard Deviation 19.77 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | ALT, Cycle 3 Day 1, n=3, 1 | 4.7 International units per Liter | Standard Deviation 6.11 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | ALT, Cycle 4 Day 1, n=3, 0 | 2.0 International units per Liter | Standard Deviation 5 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | ALT, Cycle 5 Day 1, n=3, 0 | 5.3 International units per Liter | Standard Deviation 7.02 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | ALT, Cycle 6 Day1, n=2, 0 | 2.0 International units per Liter | Standard Deviation 4.24 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | AST, Cycle 2 Day 1, n=6, 2 | 4.8 International units per Liter | Standard Deviation 5.81 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | AST, Cycle 3 Day 1, n=3, 1 | 2.0 International units per Liter | Standard Deviation 2.65 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | Alkaline Phosphatase, Cycle 2 Day 1, n=6, 2 | -53.5 International units per Liter | Standard Deviation 221.32 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | LDH, Cycle 2 Day 1, n=3, 2 | -625.0 International units per Liter | Standard Deviation 847.11 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | Alkaline Phosphatase, Cycle 3 Day 1, n=3, 1 | 57.0 International units per Liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | ALT, Cycle 3 Day 1, n=3, 1 | 4.0 International units per Liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | AST, Cycle 2 Day 1, n=6, 2 | -25.0 International units per Liter | Standard Deviation 38.18 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | LDH, Cycle 3 Day 1, n=3, 1 | -9.0 International units per Liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | AST, Cycle 3 Day 1, n=3, 1 | 4.0 International units per Liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | ALT, Cycle 2 Day 1, n=6, 2 | -6.5 International units per Liter | Standard Deviation 20.51 |
Secondary
Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase | Cycle 5 Day 1, n=3, 0 | 3.0 Units per Liter | Standard Deviation 5.57 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase | Cycle 6 Day1, n=2, 0 | -2.5 Units per Liter | Standard Deviation 31.82 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase | Cycle 3 Day 1, n=3, 1 | -7.0 Units per Liter | Standard Deviation 14.18 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase | Cycle 2 Day 1, n=4, 2 | -1.0 Units per Liter | Standard Deviation 16.39 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase | Cycle 4 Day 1, n=3, 0 | -2.3 Units per Liter | Standard Deviation 16.77 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase | Cycle 3 Day 1, n=3, 1 | -4.0 Units per Liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase | Cycle 2 Day 1, n=4, 2 | -2.5 Units per Liter | Standard Deviation 6.36 |
Secondary
Change From Baseline in Clinical Chemistry Parameter of Amylase During PK Phase
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
Population: Safety Population. Only those participants with data available at specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Amylase During PK Phase | 74.4 Units per Liter | Standard Deviation 206.9 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Amylase During PK Phase | 0.3 Units per Liter | Standard Deviation 22.92 |
Secondary
Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Creatinine, Cycle 6 Day1, n=2, 0 | 5.7 Micromoles per liter | Standard Deviation 5.63 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Creatinine, Cycle 3 Day 1, n=3, 1 | 13.0 Micromoles per liter | Standard Deviation 5.03 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Creatinine, Cycle 4 Day 1, n=3, 0 | 0.9 Micromoles per liter | Standard Deviation 9.56 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Creatinine, Cycle 5 Day 1, n=3, 0 | 5.6 Micromoles per liter | Standard Deviation 2.84 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Bilirubin, Cycle 2 Day 1, n=6, 2 | 0.9 Micromoles per liter | Standard Deviation 1.79 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Bilirubin, Cycle 3 Day 1, n=3, 1 | 0.6 Micromoles per liter | Standard Deviation 2.61 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Bilirubin, Cycle 4 Day 1, n=3, 0 | 0.6 Micromoles per liter | Standard Deviation 0.99 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Bilirubin, Cycle 5 Day 1, n=3, 0 | 2.9 Micromoles per liter | Standard Deviation 0.99 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Bilirubin, Cycle 6 Day1, n=2, 0 | -0.9 Micromoles per liter | Standard Deviation 1.21 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Creatinine, Cycle 2 Day 1, n=6, 2 | 7.5 Micromoles per liter | Standard Deviation 17.93 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Bilirubin, Cycle 2 Day 1, n=6, 2 | -6.0 Micromoles per liter | Standard Deviation 8.46 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Creatinine, Cycle 3 Day 1, n=3, 1 | 0.0 Micromoles per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Bilirubin, Cycle 3 Day 1, n=3, 1 | 1.7 Micromoles per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Creatinine, Cycle 2 Day 1, n=6, 2 | 18.1 Micromoles per liter | Standard Deviation 3.13 |
Secondary
Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase
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
Population: Safety Population. Only those participants with data available at specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase | Bilirubin | 0.6 Micromoles per liter | Standard Deviation 3.41 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase | Creatinine | -1.9 Micromoles per liter | Standard Deviation 10.87 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase | Bilirubin | 8.3 Micromoles per liter | Standard Deviation 9.47 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase | Creatinine | -0.7 Micromoles per liter | Standard Deviation 17.19 |
Secondary
Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Albumin, Cycle 6 Day1, n=2, 0 | 17.0 Grams per liter | Standard Deviation 16.97 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Albumin, Cycle 3 Day 1, n=3, 1 | 1.0 Grams per liter | Standard Deviation 2.65 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Albumin, Cycle 4 Day 1, n=3, 0 | 2.7 Grams per liter | Standard Deviation 3.21 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Albumin, Cycle 5 Day 1, n=3, 0 | 4.7 Grams per liter | Standard Deviation 2.52 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Protein, Cycle 2 Day 1, n=6, 2 | -1.0 Grams per liter | Standard Deviation 6.96 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Protein, Cycle 3 Day 1, n=3, 1 | -2.0 Grams per liter | Standard Deviation 3.46 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Protein, Cycle 4 Day 1, n=3, 0 | 1.0 Grams per liter | Standard Deviation 3.61 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Protein, Cycle 5 Day 1, n=3, 0 | 4.0 Grams per liter | Standard Deviation 2.65 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Protein, Cycle 6 Day1, n=2, 0 | 0.0 Grams per liter | Standard Deviation 2.83 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Albumin, Cycle 2 Day 1, n=6, 2 | 0.3 Grams per liter | Standard Deviation 4.37 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Protein, Cycle 2 Day 1, n=6, 2 | -2.0 Grams per liter | Standard Deviation 0 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Albumin, Cycle 3 Day 1, n=3, 1 | -1.0 Grams per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Protein, Cycle 3 Day 1, n=3, 1 | -5.0 Grams per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Albumin, Cycle 2 Day 1, n=6, 2 | -1.0 Grams per liter | Standard Deviation 0 |
Secondary
Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase
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
Population: Safety Population. Only those participants with data available at specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase | Protein | -1.0 Grams per liter | Standard Deviation 4.24 |
| Participants With Normal Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase | Albumin | -0.9 Grams per liter | Standard Deviation 2.03 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase | Protein | -3.5 Grams per liter | Standard Deviation 5.55 |
| Participants With Impaired Hepatic Function | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase | Albumin | -2.3 Grams per liter | Standard Deviation 3.45 |
Secondary
Change From Baseline in Hb During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 6 Day1, n=2, 0 | 3.0 Grams per liter | Standard Deviation 7.07 |
| Participants With Normal Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 2 Day 1, n=6, 2 | -8.0 Grams per liter | Standard Deviation 14.93 |
| Participants With Normal Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 3 Day 1, n=3, 1 | -16.7 Grams per liter | Standard Deviation 12.1 |
| Participants With Normal Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 4 Day 1, n=3, 0 | -10.7 Grams per liter | Standard Deviation 11.06 |
| Participants With Normal Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 5 Day 1, n=3, 0 | -3.7 Grams per liter | Standard Deviation 2.08 |
| Participants With Normal Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 1 Day 15, n=8, 4 | -0.5 Grams per liter | Standard Deviation 6.32 |
| Participants With Normal Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 1 Day 8, n=8, 5 | 4.3 Grams per liter | Standard Deviation 5.78 |
| Participants With Normal Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 1 Day 21, n=7, 4 | -2.6 Grams per liter | Standard Deviation 12.91 |
| Participants With Impaired Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 1 Day 15, n=8, 4 | -8.3 Grams per liter | Standard Deviation 15.73 |
| Participants With Impaired Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 3 Day 1, n=3, 1 | -10.0 Grams per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 1 Day 8, n=8, 5 | 1.0 Grams per liter | Standard Deviation 8.89 |
| Participants With Impaired Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 2 Day 1, n=6, 2 | -15.0 Grams per liter | Standard Deviation 1.41 |
| Participants With Impaired Hepatic Function | Change From Baseline in Hb During Extension Phase | Cycle 1 Day 21, n=7, 4 | -22.3 Grams per liter | Standard Deviation 17.19 |
Secondary
Change From Baseline in Hemoglobin (Hb) During PK Phase
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
Population: Safety Population. Only those participants with data available at specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Hemoglobin (Hb) During PK Phase | -0.5 Grams per liter | Standard Deviation 7.82 |
| Participants With Impaired Hepatic Function | Change From Baseline in Hemoglobin (Hb) During PK Phase | 0.6 Grams per liter | Standard Deviation 7.65 |
Secondary
Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase
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
Population: Safety Population. Only those participants with data available at specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Monocytes | 0.1 10^9 cells per liter | Standard Deviation 0.32 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Platelets | -18.4 10^9 cells per liter | Standard Deviation 95.41 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Neutrophils | -0.5 10^9 cells per liter | Standard Deviation 2.13 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Leukocyte | -0.2 10^9 cells per liter | Standard Deviation 2.04 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Lymphocytes | 0.2 10^9 cells per liter | Standard Deviation 0.38 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Leukocyte | -0.8 10^9 cells per liter | Standard Deviation 2.16 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Lymphocytes | -0.1 10^9 cells per liter | Standard Deviation 0.15 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Monocytes | -0.1 10^9 cells per liter | Standard Deviation 0.24 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Neutrophils | -0.7 10^9 cells per liter | Standard Deviation 1.89 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Platelets | -23.4 10^9 cells per liter | Standard Deviation 60.31 |
Secondary
Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 6 Day1, n=2, 0 | -0.3 10^9 cells per liter | Standard Deviation 1.48 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 1 Day 8, n=7, 5 | -0.2 10^9 cells per liter | Standard Deviation 0.36 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 5 Day 1, n=3, 0 | -0.1 10^9 cells per liter | Standard Deviation 0.1 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 6 Day1, n=2, 0 | -0.1 10^9 cells per liter | Standard Deviation 0.16 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 1 Day 8, n=7, 5 | 0.4 10^9 cells per liter | Standard Deviation 0.87 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 1 Day 15, n=8, 4 | 0.3 10^9 cells per liter | Standard Deviation 1.01 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 1 Day 21, n=7, 4 | -0.6 10^9 cells per liter | Standard Deviation 1.92 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 2 Day 1, n=6, 2 | 0.6 10^9 cells per liter | Standard Deviation 2.03 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 3 Day 1, n=3, 1 | -0.0 10^9 cells per liter | Standard Deviation 1.7 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 4 Day 1, n=3, 0 | -0.4 10^9 cells per liter | Standard Deviation 0.51 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 5 Day 1, n=3, 0 | 0.5 10^9 cells per liter | Standard Deviation 0.27 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 6 Day1, n=2, 0 | -0.1 10^9 cells per liter | Standard Deviation 0.78 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 1 Day 8, n=8, 5 | 12.0 10^9 cells per liter | Standard Deviation 21.75 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 1 Day 15, n=8, 4 | -58.1 10^9 cells per liter | Standard Deviation 118.98 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 1 Day 21, n=7, 4 | -81.9 10^9 cells per liter | Standard Deviation 113.91 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 3 Day 1, n=3, 1 | -46.3 10^9 cells per liter | Standard Deviation 36.46 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 4 Day 1, n=3, 0 | 34.0 10^9 cells per liter | Standard Deviation 43.92 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 5 Day 1, n=3, 0 | 45.7 10^9 cells per liter | Standard Deviation 22.68 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 6 Day1, n=2, 0 | 34.0 10^9 cells per liter | Standard Deviation 42.43 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 1 Day 8, n=8, 5 | 0.4 10^9 cells per liter | Standard Deviation 1.76 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 1 Day 15, n=8, 4 | -0.1 10^9 cells per liter | Standard Deviation 1.25 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 1 Day 21, n=7, 4 | -1.0 10^9 cells per liter | Standard Deviation 2.05 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 2 Day 1, n=6, 2 | 0.5 10^9 cells per liter | Standard Deviation 1.96 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 3 Day 1, n=3, 1 | -0.5 10^9 cells per liter | Standard Deviation 1.67 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 4 Day 1, n=3, 0 | -0.4 10^9 cells per liter | Standard Deviation 0.76 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 5 Day 1, n=3, 0 | 0.9 10^9 cells per liter | Standard Deviation 0.31 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 2 Day 1, n=6, 2 | 55.3 10^9 cells per liter | Standard Deviation 128.24 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 1 Day 15, n=8, 4 | -0.1 10^9 cells per liter | Standard Deviation 0.37 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 1 Day 21, n=7, 4 | -0.1 10^9 cells per liter | Standard Deviation 0.25 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 2 Day 1, n=6, 2 | -0.1 10^9 cells per liter | Standard Deviation 0.33 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 3 Day 1, n=3, 1 | -0.3 10^9 cells per liter | Standard Deviation 0.24 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 4 Day 1, n=3, 0 | 0.0 10^9 cells per liter | Standard Deviation 0.33 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 5 Day 1, n=3, 0 | 0.3 10^9 cells per liter | Standard Deviation 0.3 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 6 Day1, n=2, 0 | -0.0 10^9 cells per liter | Standard Deviation 0.54 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 1 Day 8, n=7, 5 | -0.1 10^9 cells per liter | Standard Deviation 0.2 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 1 Day 15, n=8, 4 | -0.2 10^9 cells per liter | Standard Deviation 0.28 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 1 Day 21, n=7, 4 | -0.2 10^9 cells per liter | Standard Deviation 0.2 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 2 Day 1, n=6, 2 | -0.1 10^9 cells per liter | Standard Deviation 0.14 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 3 Day 1, n=3, 1 | -0.2 10^9 cells per liter | Standard Deviation 0.06 |
| Participants With Normal Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 4 Day 1, n=3, 0 | -0.0 10^9 cells per liter | Standard Deviation 0.09 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 1 Day 8, n=7, 5 | -0.1 10^9 cells per liter | Standard Deviation 0.22 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 2 Day 1, n=6, 2 | -1.9 10^9 cells per liter | Standard Deviation 1.91 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 1 Day 15, n=8, 4 | -0.0 10^9 cells per liter | Standard Deviation 0.48 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 1 Day 8, n=7, 5 | 0.4 10^9 cells per liter | Standard Deviation 0.44 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 1 Day 21, n=7, 4 | -0.2 10^9 cells per liter | Standard Deviation 0.2 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 1 Day 15, n=8, 4 | -8.3 10^9 cells per liter | Standard Deviation 63.33 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 2 Day 1, n=6, 2 | 0.1 10^9 cells per liter | Standard Deviation 0.04 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 1 Day 15, n=8, 4 | 0.5 10^9 cells per liter | Standard Deviation 0.73 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Lymphocytes, Cycle 3 Day 1, n=3, 1 | 0.2 10^9 cells per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 1 Day 21, n=7, 4 | -0.5 10^9 cells per liter | Standard Deviation 1.36 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 1 Day 21, n=7, 4 | -0.2 10^9 cells per liter | Standard Deviation 0.81 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 1 Day 21, n=7, 4 | -19.3 10^9 cells per liter | Standard Deviation 57.7 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 2 Day 1, n=6, 2 | -1.8 10^9 cells per liter | Standard Deviation 1.94 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 1 Day 8, n=7, 5 | 0.0 10^9 cells per liter | Standard Deviation 0.11 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 2 Day 1, n=6, 2 | -102.5 10^9 cells per liter | Standard Deviation 130.81 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 1 Day 15, n=8, 4 | -0.1 10^9 cells per liter | Standard Deviation 0.22 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Neutrophils, Cycle 3 Day 1, n=3, 1 | -0.5 10^9 cells per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 1 Day 21, n=7, 4 | -0.1 10^9 cells per liter | Standard Deviation 0.4 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 1 Day 8, n=8, 5 | 0.3 10^9 cells per liter | Standard Deviation 0.4 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 2 Day 1, n=6, 2 | -0.1 10^9 cells per liter | Standard Deviation 0.16 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 3 Day 1, n=3, 1 | 59.0 10^9 cells per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Monocytes, Cycle 3 Day 1, n=3, 1 | 0.0 10^9 cells per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 3 Day 1, n=3, 1 | -0.2 10^9 cells per liter | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Leukocytes, Cycle 1 Day 15, n=8, 4 | 0.4 10^9 cells per liter | Standard Deviation 1.28 |
| Participants With Impaired Hepatic Function | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Platelets, Cycle 1 Day 8, n=8, 5 | -0.8 10^9 cells per liter | Standard Deviation 21.32 |
Secondary
Change From Baseline in Pulse Rate During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Pulse Rate During Extension Phase | Cycle 3 Day 1, n=3, 1 | 23.0 Beats per minute | Standard Deviation 20.78 |
| Participants With Normal Hepatic Function | Change From Baseline in Pulse Rate During Extension Phase | Cycle 4 Day 1, n=3, 0 | 15.3 Beats per minute | Standard Deviation 8.08 |
| Participants With Normal Hepatic Function | Change From Baseline in Pulse Rate During Extension Phase | Cycle 5 Day 1, n=3, 0 | 9.3 Beats per minute | Standard Deviation 11.55 |
| Participants With Normal Hepatic Function | Change From Baseline in Pulse Rate During Extension Phase | Cycle 6 Day1, n=2, 0 | 16.5 Beats per minute | Standard Deviation 9.19 |
| Participants With Normal Hepatic Function | Change From Baseline in Pulse Rate During Extension Phase | Cycle 2 Day 1, n=6, 2 | 17.2 Beats per minute | Standard Deviation 10.15 |
| Participants With Impaired Hepatic Function | Change From Baseline in Pulse Rate During Extension Phase | Cycle 2 Day 1, n=6, 2 | 9.0 Beats per minute | Standard Deviation 5.66 |
| Participants With Impaired Hepatic Function | Change From Baseline in Pulse Rate During Extension Phase | Cycle 3 Day 1, n=3, 1 | 4.0 Beats per minute | — |
Secondary
Change From Baseline in Pulse Rate During PK Phase
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
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Pulse Rate During PK Phase | Day 2, n=9, 7 | 8.9 Beats per minute | Standard Deviation 11.3 |
| Participants With Normal Hepatic Function | Change From Baseline in Pulse Rate During PK Phase | Day 8, n=9, 8 | 2.8 Beats per minute | Standard Deviation 11.91 |
| Participants With Impaired Hepatic Function | Change From Baseline in Pulse Rate During PK Phase | Day 2, n=9, 7 | 1.3 Beats per minute | Standard Deviation 10.58 |
| Participants With Impaired Hepatic Function | Change From Baseline in Pulse Rate During PK Phase | Day 8, n=9, 8 | -2.3 Beats per minute | Standard Deviation 7.85 |
Secondary
Change From Baseline in SBP and DBP During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | SBP, Cycle 6 Day1, n=2, 0 | 13.0 Millimeters of mercury | Standard Deviation 1.41 |
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | SBP, Cycle 3 Day 1, n=3, 1 | 6.7 Millimeters of mercury | Standard Deviation 10.97 |
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | SBP, Cycle 4 Day 1, n=3, 0 | -2.3 Millimeters of mercury | Standard Deviation 7.57 |
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | SBP, Cycle 5 Day 1, n=3, 0 | 5.7 Millimeters of mercury | Standard Deviation 10.02 |
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | DBP, Cycle 2 Day 1, n=6, 2 | -0.2 Millimeters of mercury | Standard Deviation 3.19 |
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | DBP, Cycle 3 Day 1, n=3, 1 | 8.7 Millimeters of mercury | Standard Deviation 9.81 |
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | DBP, Cycle 4 Day 1, n=3, 0 | -0.3 Millimeters of mercury | Standard Deviation 3.06 |
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | DBP, Cycle 5 Day 1, n=3, 0 | 12.3 Millimeters of mercury | Standard Deviation 6.51 |
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | DBP, Cycle 6 Day1, n=2, 0 | 6.5 Millimeters of mercury | Standard Deviation 4.95 |
| Participants With Normal Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | SBP, Cycle 2 Day 1, n=6, 2 | -1.2 Millimeters of mercury | Standard Deviation 12.89 |
| Participants With Impaired Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | DBP, Cycle 2 Day 1, n=6, 2 | -12.0 Millimeters of mercury | Standard Deviation 12.73 |
| Participants With Impaired Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | SBP, Cycle 3 Day 1, n=3, 1 | -6.0 Millimeters of mercury | — |
| Participants With Impaired Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | DBP, Cycle 3 Day 1, n=3, 1 | -9.0 Millimeters of mercury | — |
| Participants With Impaired Hepatic Function | Change From Baseline in SBP and DBP During Extension Phase | SBP, Cycle 2 Day 1, n=6, 2 | -2.5 Millimeters of mercury | Standard Deviation 23.33 |
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase
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
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | SBP, Day 2, n=9, 7 | 5.9 Millimeters of mercury | Standard Deviation 10.79 |
| Participants With Normal Hepatic Function | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | SBP, Day 8, n=9, 8 | 0.9 Millimeters of mercury | Standard Deviation 18.58 |
| Participants With Normal Hepatic Function | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | DBP, Day 2, n=9, 7 | 3.6 Millimeters of mercury | Standard Deviation 8.38 |
| Participants With Normal Hepatic Function | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | DBP, Day 8, n=9, 8 | 2.4 Millimeters of mercury | Standard Deviation 9.08 |
| Participants With Impaired Hepatic Function | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | DBP, Day 8, n=9, 8 | -0.1 Millimeters of mercury | Standard Deviation 11.18 |
| Participants With Impaired Hepatic Function | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | SBP, Day 2, n=9, 7 | 5.7 Millimeters of mercury | Standard Deviation 10.23 |
| Participants With Impaired Hepatic Function | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | DBP, Day 2, n=9, 7 | 2.7 Millimeters of mercury | Standard Deviation 3.15 |
| Participants With Impaired Hepatic Function | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | SBP, Day 8, n=9, 8 | 0.3 Millimeters of mercury | Standard Deviation 9.69 |
Secondary
Change From Baseline in Temperature During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Temperature During Extension Phase | Cycle 5 Day 1, n=3, 0 | -0.1 Degrees Celsius | Standard Deviation 0.21 |
| Participants With Normal Hepatic Function | Change From Baseline in Temperature During Extension Phase | Cycle 6 Day1, n=2, 0 | -0.3 Degrees Celsius | Standard Deviation 0.21 |
| Participants With Normal Hepatic Function | Change From Baseline in Temperature During Extension Phase | Cycle 3 Day 1, n=3, 1 | -0.1 Degrees Celsius | Standard Deviation 0.26 |
| Participants With Normal Hepatic Function | Change From Baseline in Temperature During Extension Phase | Cycle 2 Day 1, n=6, 2 | -0.3 Degrees Celsius | Standard Deviation 0.77 |
| Participants With Normal Hepatic Function | Change From Baseline in Temperature During Extension Phase | Cycle 4 Day 1, n=3, 0 | -0.0 Degrees Celsius | Standard Deviation 0.38 |
| Participants With Impaired Hepatic Function | Change From Baseline in Temperature During Extension Phase | Cycle 3 Day 1, n=3, 1 | 0.0 Degrees Celsius | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Temperature During Extension Phase | Cycle 2 Day 1, n=6, 2 | 0.1 Degrees Celsius | Standard Deviation 0.07 |
Secondary
Change From Baseline in Weight During Extension Phase
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Weight During Extension Phase | Cycle 5 Day 1, n=3, 0 | -3.3 Kilograms | Standard Deviation 2.91 |
| Participants With Normal Hepatic Function | Change From Baseline in Weight During Extension Phase | Cycle 6 Day1, n=2, 0 | -0.4 Kilograms | Standard Deviation 0.92 |
| Participants With Normal Hepatic Function | Change From Baseline in Weight During Extension Phase | Cycle 3 Day 1, n=3, 1 | -0.3 Kilograms | Standard Deviation 1 |
| Participants With Normal Hepatic Function | Change From Baseline in Weight During Extension Phase | Cycle 2 Day 1, n=6, 2 | -1.6 Kilograms | Standard Deviation 1.74 |
| Participants With Normal Hepatic Function | Change From Baseline in Weight During Extension Phase | Cycle 4 Day 1, n=3, 0 | -2.3 Kilograms | Standard Deviation 0.85 |
| Participants With Impaired Hepatic Function | Change From Baseline in Weight During Extension Phase | Cycle 3 Day 1, n=3, 1 | -4.5 Kilograms | — |
| Participants With Impaired Hepatic Function | Change From Baseline in Weight During Extension Phase | Cycle 2 Day 1, n=6, 2 | -4.6 Kilograms | Standard Deviation 4.31 |
Secondary
Change From Baseline in Weight During PK Phase
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
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline in Weight During PK Phase | Day 2, n=8, 6 | -0.0 Kilograms | Standard Deviation 0.58 |
| Participants With Normal Hepatic Function | Change From Baseline in Weight During PK Phase | Day 8, n=9, 8 | -0.0 Kilograms | Standard Deviation 1.14 |
| Participants With Impaired Hepatic Function | Change From Baseline in Weight During PK Phase | Day 2, n=8, 6 | 0.8 Kilograms | Standard Deviation 0.87 |
| Participants With Impaired Hepatic Function | Change From Baseline in Weight During PK Phase | Day 8, n=9, 8 | 0.3 Kilograms | Standard Deviation 1.3 |
Secondary
Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase
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
Population: Safety Population for extension phase consisted of all participants who received atleast one dose of the investigational drug niraparib during the extension phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Normal Hepatic Function | Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase | Any Non-SAEs | 8 Participants |
| Participants With Normal Hepatic Function | Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase | Any SAE | 3 Participants |
| Participants With Normal Hepatic Function | Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase | Any Discontinuations due to AE | 0 Participants |
| Participants With Impaired Hepatic Function | Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase | Any Non-SAEs | 7 Participants |
| Participants With Impaired Hepatic Function | Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase | Any SAE | 2 Participants |
| Participants With Impaired Hepatic Function | Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase | Any Discontinuations due to AE | 1 Participants |
Secondary
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
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
Population: Safety Population for PK phase consisted of all participants who received atleast one dose of the investigational drug niraparib during the PK phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Normal Hepatic Function | 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 | Any Non -SAEs | 5 Participants |
| Participants With Normal Hepatic Function | 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 | Any SAE | 1 Participants |
| Participants With Normal Hepatic Function | 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 | Any Discontinuations due to AE | 1 Participants |
| Participants With Impaired Hepatic Function | 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 | Any Non -SAEs | 3 Participants |
| Participants With Impaired Hepatic Function | 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 | Any SAE | 0 Participants |
| Participants With Impaired Hepatic Function | 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 | Any Discontinuations due to AE | 0 Participants |
Other Pre-specified
Clearance of Unbound Niraparib and M1 (CLfu/F) During PK Phase
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
Population: PK population.
Other Pre-specified
Plasma Protein Unbound Fraction (Fu) of Niraparib and M1 During PK Phase
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
Population: PK population.