Advanced Solid Tumors
Conditions
Brief summary
This is a trial to investigate the pharmacokinetics (PK) and the safety of talazoparib in patients with advanced solid tumors and impaired hepatic function.
Detailed description
At the end of the study, patients with no clinically significant toxicities, no contraindications to continue treatment with talazoparib, and no disease progression (underlying cancer progression) may be eligible to continue talazoparib treatment in a separate open-label extension study. The decision to allow the patient to continue dosing with talazoparib in an open-label extension (OLE) study will be based on potential overall benefit-risk and patient meeting eligibility criteria for OLE.
Interventions
DRUGTalazoparib
Daily oral doses of talazoparib 0.5 mg
Sponsors
Medivation, Inc.
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed and dated Informed Consent Form (by the patient or a legally acceptable representative as per the local regulations). 2. Female or male at least 18 years of age. 3. Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator 4. Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2. 5. Expected life expectancy of ≥ 3 months. 6. Able to swallow the study drug (no contraindication to oral agents). 7. Hepatic function at screening and enrollment as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria. 8. Adequate other organ function at screening and enrollment. 9. Female patients of childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception from the time of the first dose of study drug through 7 months after the last dose of study drug. 10. Male patients must agree to use a condom when having sex with a pregnant woman or with a non-pregnant female partner of childbearing potential, from 21 days before the first dose of study drug through 4 months after last dose of study drug. 11. Female patients must not be breastfeeding at screening nor during the study participation until 7 months after the last dose of the study drug. 12. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Exclusion criteria
1. Treatment within 14 days or five half lives prior to enrollment whichever is longer with any type of systemic anticancer-therapy or any investigational drug 2. Have not recovered (recovery is defined as CTCAE grade ≤ 1) from the acute toxicities of previous anticancer standard or investigational therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements. 3. Major surgery within 28 days prior to enrollment. 4. Serious accompanying cardiac disorder 5. Active known or suspected brain metastasis or active leptomeningeal disease needing treatment 6. Symptomatic or impending spinal cord compression or cauda equine syndrome 7. Has undergone a liver transplant, kidney transplant or nephrectomy. 8. Prior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor. 9. Known myelodysplastic syndrome 10. Seropositive for human immunodeficiency virus (HIV). 11. Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol. 12. Gastrointestinal disorder affecting absorption. 13. Known or suspected hypersensitivity to any of the talazoparib capsule components. 14. Any condition or reason that interferes with ability to participate in the study, tolerate treatment or assessments associated with the protocol, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Medical Monitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22 | Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22 | AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. |
| Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22 | Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22 | Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu\*Cmax. |
| Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22 | Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22 | AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu\*AUC0-24. fu= Fraction of Unbound (fu) Plasma. |
| Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22 | Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22 | Cmax was defined as the maximum observed plasma concentration of talazoparib. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fraction of Unbound (fu) Plasma Talazoparib on Day 1 | Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1 | Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%). |
| Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1 | Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1 | AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu\*AUC0-24. |
| Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1 | Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1 | Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu\*Cmax |
| Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Pre-dose on Day 8, 15 and 22 | Ctrough was defined as plasma trough (pre-dose) concentration of talazoparib. Acceptance criteria for Ctrough on Day 15 and Day 22: received 10 consecutive days of dosing immediately before PK sampling day; Sample drawn within 24 +/-2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day. Ctrough on Day 8: received 7 consecutive days of dosing immediately before PK sampling day; sample drawn within 24 +/- 2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22 | Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22 | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. |
| Fraction of Unbound (fu) Plasma Talazoparib on Day 22 | Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22 | Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%). |
| Accumulation Ratio (Rac) of Plasma Talazoparib | Pre-dose (within 60 minutes prior to dose) on Day 1, pre-dose(24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose) on Day 22 and 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Days 1 and 22 | Accumulation ratio for AUC0-24 was calculated as area under the curve from time zero to 24 hours on Day 22 divided by area under the curve from time zero to 24 hours on Day 1. |
| Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22 | Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 22 | Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose. |
| Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22 | Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22 | Talazoparib clearance is a measure of the rate at which talazoparib is metabolized or eliminated by normal biological processes. |
| Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1 | A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1 | Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose. |
| Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1 | A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1 | Ae0-24% was defined as the amount of talazoparib excreted in urine from time 0 to 24 hours expressed as percentage of administered dose. |
| Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22 | Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours (hrs) on Day 22 | Ae 0-24% was defined as the amount of talazoparib excreted in urine from time 0 to 24 hours expressed as percentage of administered dose. |
| Renal Clearance (CLr) of Talazoparib on Day 22 | Ae: Post-dose at any time between 0 to 12, 12 to 24 hrs on Day 22; AUC0-24: Pre-dose (24 hrs +/- 60 minutes from previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, any time between 8 to12, 24 hrs post-dose on Day 22 | Renal clearance was calculated as cumulative amount of drug excreted in urine during the 24 hours dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to 24 hours post dose (AUC0-24). |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Baseline up to 30 days after last dose of study drug (up to 52 days) | Clinically significant laboratory abnormalities included aspartate transaminase (AST) or alanine aminotransferase (ALT) \>=3 times ULN (\>5 \*ULN if baseline ALT/AST is \>3 \*ULN) and total bilirubin (TBL) \>2 times ULN or INR \>1.5, AST or ALT \>=3 times ULN with signs and symptoms consistent with hepatitis and/or eosinophilia (\>=500 eosinophils/microliter). |
| Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Baseline, Day 2, 8, 15, 22 and End of Study (Day 52) | Systolic blood pressure and diastolic blood pressure were evaluated for examination of vital signs. |
| Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Baseline, Day 2, 8, 15, 22 and End of Study (Day 52) | Heart rate was measured in beats per minute. |
| Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Baseline, Day 8, 15, 22 and End of Study (Day 52) | Respiratory rate was measured in terms of breaths per minute. |
| Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Baseline, Day 8, 15, 22 and End of Study (Day 52) | — |
| Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | Baseline up to 30 days after last dose of study drug (up to 52 days) | Pre-specified 12-Lead electrocardiogram (ECG) Criteria: QTCF (Fridericia's correction formula) : \>=450 to \<480 milliseconds, \>=480 to \<500 milliseconds, \>=500 milliseconds, increase from baseline \>=30 - \<60, increase from baseline \>=60, PR interval: \>=300 milliseconds, increase from baseline \>=25%; QRS duration: \>=140 milliseconds, increase from baseline \>=50%; QT interval: \>=500 milliseconds; QT Interval: \>= 500 milliseconds. |
| Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening (2 to 28 days prior to Day 1), Day -1 (1 day prior to Day 1), safety follow up (Visit up to Day 52) | As per ECOG, participant's performance status was measured as: 0=fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature, e.g., light housework, office work; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair. |
| Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22 | Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22 | Clearance of unbound talazoparib is a measure of the rate at which unbound talazoparib is metabolized or eliminated by normal biological processes. |
| Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1 | Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1 | AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. |
| Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1 | Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1 | Cmax was defined as the maximum observed plasma concentration of talazoparib. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1 | Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1 | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to 30 days after last dose of study drug (up to 52 days) | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. TEAEs were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs. |
| Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs | Baseline up to 30 days after last dose of study drug (up to 52 days) | A treatment-related adverse event was any untoward medical occurrence attributed to talazoparib in a participant who received talazoparib. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; Congenital anomaly. Relatedness to talazoparib was assessed by the investigator. |
| Number of Participants With TEAEs Resulting in Death | Baseline up to 30 days after last dose of study drug (up to 52 days) | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs resulting in death are reported. |
| Number of Participants With TEAEs Leading to Study Drug Discontinuation | Baseline up to 30 days after last dose of study drug (up to 52 days) | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs leading to study drug discontinuation are reported. |
Countries
United States
Participant flow
Pre-assignment details
Participants with advanced solid tumors and impaired hepatic function were enrolled. Participants were assigned to 1 of the 4 groups based on their hepatic function as per the national cancer institute organ dysfunction working group (NCI-ODWG) classification.
Participants by arm
| Arm | Count |
|---|---|
| Talazoparib: Normal Hepatic Function Participants with TB and AST \<=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. | 7 |
| Talazoparib: Mild Hepatic Impairment Participants with TB \<=ULN and AST greater than (\>) ULN or TB \>1.0 to 1.5\* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days. | 10 |
| Talazoparib: Moderate Hepatic Impairment Participants with TB \>1.5 to 3.0 \*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days. | 5 |
| Talazoparib: Severe Hepatic Impairment Participants with TB \>3\*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days. | 16 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 8 |
| Overall Study | Death | 0 | 0 | 1 | 1 |
| Overall Study | Progressive Disease | 1 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Talazoparib: Normal Hepatic Function | Total | Talazoparib: Severe Hepatic Impairment | Talazoparib: Moderate Hepatic Impairment | Talazoparib: Mild Hepatic Impairment |
|---|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 7.61 | 56.1 years STANDARD_DEVIATION 12.4 | 52.7 years STANDARD_DEVIATION 11.98 | 60.4 years STANDARD_DEVIATION 6.31 | 56.6 years STANDARD_DEVIATION 17.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 1 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 28 Participants | 14 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 4 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 31 Participants | 13 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 5 Participants | 26 Participants | 9 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 12 Participants | 7 Participants | 0 Participants | 3 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 / 7 | 0 / 10 | 1 / 5 | 7 / 16 |
| other Total, other adverse events | 6 / 7 | 7 / 10 | 3 / 5 | 10 / 16 |
| serious Total, serious adverse events | 1 / 7 | 3 / 10 | 2 / 5 | 13 / 16 |
Outcome results
Primary
Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Population: Pharmacokinetic (PK) evaluable analysis population included all enrolled participants who completed Day 22 visit, missed less than 5 consecutive doses, received at least 10 consecutive days of 0.5 mg talazoparib daily dose immediately preceding Day 22 visit without dose interruption, not vomited talazoparib dose on Day 1 and last day of dose, at least 85% of total plasma PK samples collection was reported and provided at least 1 of talazoparib PK parameters of primary interest from Day 22 visit.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22 | 111.8 nanogram*hour per milliliter | Geometric Coefficient of Variation 30 |
| Talazoparib: Mild Hepatic Impairment | Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22 | 159.0 nanogram*hour per milliliter | Geometric Coefficient of Variation 99 |
| Talazoparib: Moderate Hepatic Impairment | Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22 | 123.6 nanogram*hour per milliliter | Geometric Coefficient of Variation 30 |
| Talazoparib: Severe Hepatic Impairment | Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22 | NA nanogram*hour per milliliter | — |
Comparison: AUC0-24 was natural log-transformed and analyzed using an analysis of variance (ANOVA) model with hepatic function group as a fixed effect.90% CI: [79.92, 252.98]
Comparison: AUC0-24 was natural log-transformed and analyzed using an analysis of variance (ANOVA) model with hepatic function group as a fixed effect.90% CI: [54.58, 223.85]
Primary
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22
Cmax was defined as the maximum observed plasma concentration of talazoparib.
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Population: PK evaluable analysis population included all enrolled participants who completed Day 22 visit, missed less than 5 consecutive doses, received at least 10 consecutive days of 0.5 mg talazoparib daily dose immediately preceding Day 22 visit without dose interruption, not vomited talazoparib dose on Day 1 and last day of dose, at least 85% of total plasma PK samples collection was reported and provided at least 1 of talazoparib PK parameters of primary interest from Day 22 visit.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22 | 10.30 nanogram per milliliter | Geometric Coefficient of Variation 23 |
| Talazoparib: Mild Hepatic Impairment | Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22 | 11.30 nanogram per milliliter | Geometric Coefficient of Variation 65 |
| Talazoparib: Moderate Hepatic Impairment | Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22 | 13.56 nanogram per milliliter | Geometric Coefficient of Variation 23 |
| Talazoparib: Severe Hepatic Impairment | Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22 | NA nanogram per milliliter | — |
Comparison: Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [70.93, 169.84]
Comparison: Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [77.14, 224.74]
Primary
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22
AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu\*AUC0-24. fu= Fraction of Unbound (fu) Plasma.
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Population: PK evaluable analysis population included all enrolled participants who completed Day 22 visit, missed less than 5 consecutive doses, received at least 10 consecutive days of 0.5 mg talazoparib daily dose immediately preceding Day 22 visit without dose interruption, not vomited talazoparib dose on Day 1 and last day of dose, at least 85% of total plasma PK samples collection was reported and provided at least 1 of talazoparib PK parameters of primary interest from Day 22 visit.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22 | 30.17 nanogram*hour per milliliter | Geometric Coefficient of Variation 11 |
| Talazoparib: Mild Hepatic Impairment | Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22 | 45.08 nanogram*hour per milliliter | Geometric Coefficient of Variation 84 |
| Talazoparib: Moderate Hepatic Impairment | Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22 | 33.50 nanogram*hour per milliliter | Geometric Coefficient of Variation 35 |
| Talazoparib: Severe Hepatic Impairment | Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22 | NA nanogram*hour per milliliter | — |
Comparison: AUC0-24u was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [91.49, 243.93]
Comparison: AUC0-24u was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [60.91, 202.43]
Primary
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu\*Cmax.
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Population: PK evaluable analysis population included all enrolled participants who completed Day 22 visit, missed less than 5 consecutive doses, received at least 10 consecutive days of 0.5 mg talazoparib daily dose immediately preceding Day 22 visit without dose interruption, not vomited talazoparib dose on Day 1 and last day of dose, at least 85% of total plasma PK samples collection was reported and provided at least 1 of talazoparib PK parameters of primary interest from Day 22 visit.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22 | 2.778 nanogram per milliliter | Geometric Coefficient of Variation 27 |
| Talazoparib: Mild Hepatic Impairment | Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22 | 3.204 nanogram per milliliter | Geometric Coefficient of Variation 56 |
| Talazoparib: Moderate Hepatic Impairment | Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22 | 3.675 nanogram per milliliter | Geometric Coefficient of Variation 28 |
| Talazoparib: Severe Hepatic Impairment | Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22 | NA nanogram per milliliter | — |
Comparison: Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [77.95, 170.6]
Comparison: Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [81.87, 213.67]
Secondary
Accumulation Ratio (Rac) of Plasma Talazoparib
Accumulation ratio for AUC0-24 was calculated as area under the curve from time zero to 24 hours on Day 22 divided by area under the curve from time zero to 24 hours on Day 1.
Time frame: Pre-dose (within 60 minutes prior to dose) on Day 1, pre-dose(24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose) on Day 22 and 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Days 1 and 22
Population: PK evaluable analysis population was analyzed. Here, Overall Number of Participants Analyzed =participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Accumulation Ratio (Rac) of Plasma Talazoparib | 5.070 ratio | Geometric Coefficient of Variation 24 |
| Talazoparib: Mild Hepatic Impairment | Accumulation Ratio (Rac) of Plasma Talazoparib | 5.134 ratio | Geometric Coefficient of Variation 68 |
| Talazoparib: Moderate Hepatic Impairment | Accumulation Ratio (Rac) of Plasma Talazoparib | 4.771 ratio | Geometric Coefficient of Variation 31 |
| Talazoparib: Severe Hepatic Impairment | Accumulation Ratio (Rac) of Plasma Talazoparib | NA ratio | — |
Secondary
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1
Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose.
Time frame: A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1
Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of talazoparib and had at least 1 of the talazoparib PK parameters. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1 | 0.03816 milligram | Geometric Coefficient of Variation 79 |
| Talazoparib: Mild Hepatic Impairment | Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1 | 0.03534 milligram | Geometric Coefficient of Variation 71 |
| Talazoparib: Moderate Hepatic Impairment | Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1 | 0.04292 milligram | Geometric Coefficient of Variation 85 |
| Talazoparib: Severe Hepatic Impairment | Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1 | 0.02319 milligram | Geometric Coefficient of Variation 107 |
Secondary
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22
Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose.
Time frame: Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 22
Population: PK evaluable analysis population was analyzed. Here, Overall Number of Participants Analyzed =participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22 | 0.2229 milligram | Geometric Coefficient of Variation 30 |
| Talazoparib: Mild Hepatic Impairment | Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22 | 0.1819 milligram | Geometric Coefficient of Variation 34 |
| Talazoparib: Moderate Hepatic Impairment | Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22 | 0.1867 milligram | Geometric Coefficient of Variation 32 |
| Talazoparib: Severe Hepatic Impairment | Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22 | NA milligram | — |
Secondary
Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22
Talazoparib clearance is a measure of the rate at which talazoparib is metabolized or eliminated by normal biological processes.
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Population: PK evaluable analysis population included all enrolled participants who completed Day 22 visit, missed less than 5 consecutive doses, received at least 10 consecutive days of 0.5 mg talazoparib daily dose immediately preceding Day 22 visit without dose interruption, not vomited talazoparib dose on Day 1 and last day of dose, at least 85% of total plasma PK samples collection was reported and provided at least 1 of talazoparib PK parameters of primary interest from Day 22 visit.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22 | 5.070 liter per hour | Geometric Coefficient of Variation 24 |
| Talazoparib: Mild Hepatic Impairment | Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22 | 5.134 liter per hour | Geometric Coefficient of Variation 68 |
| Talazoparib: Moderate Hepatic Impairment | Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22 | 4.771 liter per hour | Geometric Coefficient of Variation 31 |
| Talazoparib: Severe Hepatic Impairment | Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22 | NA liter per hour | — |
Secondary
Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of talazoparib and had at least 1 of the talazoparib PK parameters. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1 | 22.21 nanogram*hour per milliliter | Geometric Coefficient of Variation 41 |
| Talazoparib: Mild Hepatic Impairment | Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1 | 27.63 nanogram*hour per milliliter | Geometric Coefficient of Variation 38 |
| Talazoparib: Moderate Hepatic Impairment | Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1 | 25.20 nanogram*hour per milliliter | Geometric Coefficient of Variation 7 |
| Talazoparib: Severe Hepatic Impairment | Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1 | 21.26 nanogram*hour per milliliter | Geometric Coefficient of Variation 58 |
Comparison: AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [85.19, 181.66]
Comparison: AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [73.9, 174.07]
Comparison: AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [67.9, 134.83]
Secondary
Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study
Systolic blood pressure and diastolic blood pressure were evaluated for examination of vital signs.
Time frame: Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
Population: Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 15 | -8.4 millimeter of mercury (mmHg) | Standard Deviation 8.64 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 2 | -12.3 millimeter of mercury (mmHg) | Standard Deviation 17.72 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Baseline | 75.9 millimeter of mercury (mmHg) | Standard Deviation 12.52 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at end of study (Day 52) | -0.8 millimeter of mercury (mmHg) | Standard Deviation 18.36 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 22 | -7.5 millimeter of mercury (mmHg) | Standard Deviation 15.1 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at end of study (Day 52) | -0.3 millimeter of mercury (mmHg) | Standard Deviation 8.26 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 22 | -3.5 millimeter of mercury (mmHg) | Standard Deviation 9.14 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 15 | -1.4 millimeter of mercury (mmHg) | Standard Deviation 6.92 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 8 | -2.0 millimeter of mercury (mmHg) | Standard Deviation 20.22 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Baseline | 128.1 millimeter of mercury (mmHg) | Standard Deviation 19.22 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 8 | -1.0 millimeter of mercury (mmHg) | Standard Deviation 12.04 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 2 | -5.0 millimeter of mercury (mmHg) | Standard Deviation 6.76 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 22 | -3.0 millimeter of mercury (mmHg) | Standard Deviation 7.82 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Baseline | 110.3 millimeter of mercury (mmHg) | Standard Deviation 11.84 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 2 | -1.1 millimeter of mercury (mmHg) | Standard Deviation 12.86 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 8 | -2.8 millimeter of mercury (mmHg) | Standard Deviation 9.85 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 15 | 0.3 millimeter of mercury (mmHg) | Standard Deviation 12.08 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 22 | -4.3 millimeter of mercury (mmHg) | Standard Deviation 14.3 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at end of study (Day 52) | 0.7 millimeter of mercury (mmHg) | Standard Deviation 14.22 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Baseline | 65.9 millimeter of mercury (mmHg) | Standard Deviation 10.77 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 2 | 4.1 millimeter of mercury (mmHg) | Standard Deviation 7.69 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 8 | 4.1 millimeter of mercury (mmHg) | Standard Deviation 6.66 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 15 | 0.9 millimeter of mercury (mmHg) | Standard Deviation 9 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at end of study (Day 52) | 1.9 millimeter of mercury (mmHg) | Standard Deviation 7.52 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 22 | -3.3 millimeter of mercury (mmHg) | Standard Deviation 15.53 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Baseline | 68.4 millimeter of mercury (mmHg) | Standard Deviation 5.59 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 2 | -4.5 millimeter of mercury (mmHg) | Standard Deviation 6.19 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 8 | -5.6 millimeter of mercury (mmHg) | Standard Deviation 11.97 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Baseline | 121.8 millimeter of mercury (mmHg) | Standard Deviation 23.15 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 8 | -0.8 millimeter of mercury (mmHg) | Standard Deviation 9.12 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 15 | 0.8 millimeter of mercury (mmHg) | Standard Deviation 10.84 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 2 | -12.5 millimeter of mercury (mmHg) | Standard Deviation 14.48 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 22 | -10.7 millimeter of mercury (mmHg) | Standard Deviation 32.56 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 15 | -6.0 millimeter of mercury (mmHg) | Standard Deviation 23.47 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 8 | -4.1 millimeter of mercury (mmHg) | Standard Deviation 9.91 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 2 | 2.2 millimeter of mercury (mmHg) | Standard Deviation 10.43 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at end of study (Day 52) | -17.0 millimeter of mercury (mmHg) | — |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 15 | -2.3 millimeter of mercury (mmHg) | Standard Deviation 13.91 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Baseline | 73.9 millimeter of mercury (mmHg) | Standard Deviation 10.6 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 8 | -5.3 millimeter of mercury (mmHg) | Standard Deviation 10.8 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 22 | -6.0 millimeter of mercury (mmHg) | Standard Deviation 11.17 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 15 | -2.1 millimeter of mercury (mmHg) | Standard Deviation 4.97 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Diastolic Blood Pressure: Change at Day 2 | -0.8 millimeter of mercury (mmHg) | Standard Deviation 7.03 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Baseline | 115.8 millimeter of mercury (mmHg) | Standard Deviation 13.57 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at end of study (Day 52) | -26.0 millimeter of mercury (mmHg) | — |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study | Systolic Blood Pressure: Change at Day 22 | -7.8 millimeter of mercury (mmHg) | Standard Deviation 17.2 |
Secondary
Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study
Heart rate was measured in beats per minute.
Time frame: Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
Population: Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 15 | 5.1 beats per minute | Standard Deviation 9.82 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 22 | 2.2 beats per minute | Standard Deviation 9.81 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at end of study (Day 52) | 8.5 beats per minute | Standard Deviation 11.9 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 8 | 1.7 beats per minute | Standard Deviation 7.78 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 2 | 3.0 beats per minute | Standard Deviation 7.64 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Baseline | 75.9 beats per minute | Standard Deviation 7.67 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 2 | 4.7 beats per minute | Standard Deviation 10.01 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 15 | -6.0 beats per minute | Standard Deviation 12.76 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at end of study (Day 52) | 3.1 beats per minute | Standard Deviation 15.56 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 22 | -9.9 beats per minute | Standard Deviation 20.38 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Baseline | 89.2 beats per minute | Standard Deviation 19.34 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 8 | 3.5 beats per minute | Standard Deviation 16.1 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 22 | -2.0 beats per minute | Standard Deviation 1 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Baseline | 87.4 beats per minute | Standard Deviation 22.13 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 2 | 1.0 beats per minute | Standard Deviation 6.16 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 8 | 1.6 beats per minute | Standard Deviation 4.67 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 15 | 2.5 beats per minute | Standard Deviation 7.05 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 15 | 3.8 beats per minute | Standard Deviation 15.52 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 8 | -2.7 beats per minute | Standard Deviation 8.79 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 22 | 2.3 beats per minute | Standard Deviation 19.16 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at Day 2 | 1.4 beats per minute | Standard Deviation 11.01 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Baseline | 92.3 beats per minute | Standard Deviation 16.76 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study | Change at end of study (Day 52) | 23.0 beats per minute | — |
Secondary
Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study
Respiratory rate was measured in terms of breaths per minute.
Time frame: Baseline, Day 8, 15, 22 and End of Study (Day 52)
Population: Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at end of study (Day 52) | -0.5 breaths per minute | Standard Deviation 1 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Baseline | 18.3 breaths per minute | Standard Deviation 2.63 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 15 | -1.6 breaths per minute | Standard Deviation 3.15 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 22 | -0.2 breaths per minute | Standard Deviation 0.98 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 8 | -0.3 breaths per minute | Standard Deviation 2.06 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 15 | -0.4 breaths per minute | Standard Deviation 1.51 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Baseline | 17.1 breaths per minute | Standard Deviation 1.2 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 8 | 0.6 breaths per minute | Standard Deviation 1.77 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 22 | -0.6 breaths per minute | Standard Deviation 1.41 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at end of study (Day 52) | 0.1 breaths per minute | Standard Deviation 1.46 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 8 | 1.2 breaths per minute | Standard Deviation 2.39 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 22 | 1.3 breaths per minute | Standard Deviation 0.58 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Baseline | 16.8 breaths per minute | Standard Deviation 0.84 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 15 | 0.3 breaths per minute | Standard Deviation 1.53 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 8 | -0.1 breaths per minute | Standard Deviation 2.19 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 22 | 1.1 breaths per minute | Standard Deviation 1.17 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at Day 15 | 0.4 breaths per minute | Standard Deviation 1.51 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Baseline | 17.4 breaths per minute | Standard Deviation 1.63 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study | Change at end of study (Day 52) | 2.0 breaths per minute | — |
Secondary
Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study
Time frame: Baseline, Day 8, 15, 22 and End of Study (Day 52)
Population: Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Baseline | 82.01 kilogram | Standard Deviation 15.749 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 8 | -0.04 kilogram | Standard Deviation 0.943 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at end of study (Day 52) | 0.48 kilogram | Standard Deviation 1.839 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 22 | -0.78 kilogram | Standard Deviation 0.546 |
| Talazoparib: Normal Hepatic Function | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 15 | -0.36 kilogram | Standard Deviation 0.621 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 22 | 0.28 kilogram | Standard Deviation 1.647 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at end of study (Day 52) | 1.81 kilogram | Standard Deviation 1.577 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 8 | -0.10 kilogram | Standard Deviation 1.865 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Baseline | 63.07 kilogram | Standard Deviation 11.493 |
| Talazoparib: Mild Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 15 | -0.09 kilogram | Standard Deviation 2.119 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 15 | -1.78 kilogram | Standard Deviation 0.9 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 22 | -1.57 kilogram | Standard Deviation 0.462 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 8 | -2.02 kilogram | Standard Deviation 1.656 |
| Talazoparib: Moderate Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Baseline | 77.78 kilogram | Standard Deviation 17.07 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at end of study (Day 52) | 0.90 kilogram | — |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 15 | -1.29 kilogram | Standard Deviation 5.025 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Baseline | 66.98 kilogram | Standard Deviation 12.979 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 8 | -1.50 kilogram | Standard Deviation 3.728 |
| Talazoparib: Severe Hepatic Impairment | Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study | Change at Day 22 | -2.06 kilogram | Standard Deviation 5.416 |
Secondary
Fraction of Unbound (fu) Plasma Talazoparib on Day 1
Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%).
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of talazoparib and had at least 1 of the talazoparib PK parameters. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Fraction of Unbound (fu) Plasma Talazoparib on Day 1 | 28.76 percentage of drug concentration | Geometric Coefficient of Variation 20 |
| Talazoparib: Mild Hepatic Impairment | Fraction of Unbound (fu) Plasma Talazoparib on Day 1 | 28.11 percentage of drug concentration | Geometric Coefficient of Variation 14 |
| Talazoparib: Moderate Hepatic Impairment | Fraction of Unbound (fu) Plasma Talazoparib on Day 1 | 27.47 percentage of drug concentration | Geometric Coefficient of Variation 15 |
| Talazoparib: Severe Hepatic Impairment | Fraction of Unbound (fu) Plasma Talazoparib on Day 1 | 34.66 percentage of drug concentration | Geometric Coefficient of Variation 17 |
Secondary
Fraction of Unbound (fu) Plasma Talazoparib on Day 22
Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%).
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Population: Analysis population included participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Fraction of Unbound (fu) Plasma Talazoparib on Day 22 | 26.98 percentage of drug concentration | Geometric Coefficient of Variation 23 |
| Talazoparib: Mild Hepatic Impairment | Fraction of Unbound (fu) Plasma Talazoparib on Day 22 | 27.71 percentage of drug concentration | Geometric Coefficient of Variation 18 |
| Talazoparib: Moderate Hepatic Impairment | Fraction of Unbound (fu) Plasma Talazoparib on Day 22 | 27.10 percentage of drug concentration | Geometric Coefficient of Variation 9 |
| Talazoparib: Severe Hepatic Impairment | Fraction of Unbound (fu) Plasma Talazoparib on Day 22 | 33.92 percentage of drug concentration | Geometric Coefficient of Variation 25 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1
Cmax was defined as the maximum observed plasma concentration of talazoparib.
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of talazoparib and had at least 1 of the talazoparib PK parameters. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1 | 3.068 nanogram per milliliter | Geometric Coefficient of Variation 66 |
| Talazoparib: Mild Hepatic Impairment | Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1 | 3.047 nanogram per milliliter | Geometric Coefficient of Variation 32 |
| Talazoparib: Moderate Hepatic Impairment | Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1 | 2.959 nanogram per milliliter | Geometric Coefficient of Variation 44 |
| Talazoparib: Severe Hepatic Impairment | Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1 | 1.965 nanogram per milliliter | Geometric Coefficient of Variation 90 |
Comparison: Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [57.74, 170.8]
Comparison: Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [52.22, 178.14]
Comparison: Cmax was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.90% CI: [39.65, 103.46]
Secondary
Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria
Pre-specified 12-Lead electrocardiogram (ECG) Criteria: QTCF (Fridericia's correction formula) : \>=450 to \<480 milliseconds, \>=480 to \<500 milliseconds, \>=500 milliseconds, increase from baseline \>=30 - \<60, increase from baseline \>=60, PR interval: \>=300 milliseconds, increase from baseline \>=25%; QRS duration: \>=140 milliseconds, increase from baseline \>=50%; QT interval: \>=500 milliseconds; QT Interval: \>= 500 milliseconds.
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis set included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=450 - <480 milliseconds | 2 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=480 - <500 milliseconds | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=500 milliseconds | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: Increase from baseline >=30 - <60 milliseconds | 2 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: Increase from baseline >=60 milliseconds | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | PR Interval: >=300 milliseconds | 1 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | PR Interval: Increase from baseline >=25% | 1 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QRS Duration: >=140 milliseconds | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QRS Duration: Increase from baseline >=50% | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QT Interval: >=500 milliseconds | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=500 milliseconds | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QRS Duration: Increase from baseline >=50% | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: Increase from baseline >=30 - <60 milliseconds | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: Increase from baseline >=60 milliseconds | 1 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | PR Interval: >=300 milliseconds | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | PR Interval: Increase from baseline >=25% | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QT Interval: >=500 milliseconds | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QRS Duration: >=140 milliseconds | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=450 - <480 milliseconds | 2 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=480 - <500 milliseconds | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QRS Duration: >=140 milliseconds | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | PR Interval: Increase from baseline >=25% | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QT Interval: >=500 milliseconds | 1 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=450 - <480 milliseconds | 1 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: Increase from baseline >=30 - <60 milliseconds | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | PR Interval: >=300 milliseconds | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QRS Duration: Increase from baseline >=50% | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=480 - <500 milliseconds | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: Increase from baseline >=60 milliseconds | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=500 milliseconds | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: Increase from baseline >=60 milliseconds | 1 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QRS Duration: >=140 milliseconds | 1 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | PR Interval: >=300 milliseconds | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QT Interval: >=500 milliseconds | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | PR Interval: Increase from baseline >=25% | 2 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=480 - <500 milliseconds | 1 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=500 milliseconds | 1 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: Increase from baseline >=30 - <60 milliseconds | 3 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QTCF: >=450 - <480 milliseconds | 4 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria | QRS Duration: Increase from baseline >=50% | 0 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities
Clinically significant laboratory abnormalities included aspartate transaminase (AST) or alanine aminotransferase (ALT) \>=3 times ULN (\>5 \*ULN if baseline ALT/AST is \>3 \*ULN) and total bilirubin (TBL) \>2 times ULN or INR \>1.5, AST or ALT \>=3 times ULN with signs and symptoms consistent with hepatitis and/or eosinophilia (\>=500 eosinophils/microliter).
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis set included all participants who received any amount of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib: Normal Hepatic Function | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Clinically Significant Laboratory Abnormalities | 3 Participants |
Secondary
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
As per ECOG, participant's performance status was measured as: 0=fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature, e.g., light housework, office work; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair.
Time frame: Screening (2 to 28 days prior to Day 1), Day -1 (1 day prior to Day 1), safety follow up (Visit up to Day 52)
Population: Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 0 | 3 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 1 | 2 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 2 | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 0 | 2 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 1 | 4 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 0 | 2 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 2 | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 1 | 5 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 2 | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 2 | 1 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 1 | 4 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 1 | 8 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 0 | 1 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 2 | 1 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 2 | 1 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 1 | 9 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 0 | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 0 | 1 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 2 | 2 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 0 | 1 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 1 | 2 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 2 | 2 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 0 | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 1 | 2 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 0 | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 1 | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 2 | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 1 | 11 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 1 | 12 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 1 | 1 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 0 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 0 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 2 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Screening | ECOG Performance Status: 2 | 4 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 4 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 3 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Safety follow up | ECOG Performance Status: 0 | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Day -1 | ECOG Performance Status: 2 | 4 Participants |
Secondary
Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22
Ae 0-24% was defined as the amount of talazoparib excreted in urine from time 0 to 24 hours expressed as percentage of administered dose.
Time frame: Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours (hrs) on Day 22
Population: PK evaluable analysis population was analyzed. Here, Overall Number of Participants Analyzed =participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22 | 44.58 percentage of dose | Geometric Coefficient of Variation 30 |
| Talazoparib: Mild Hepatic Impairment | Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22 | 36.36 percentage of dose | Geometric Coefficient of Variation 34 |
| Talazoparib: Moderate Hepatic Impairment | Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22 | 37.40 percentage of dose | Geometric Coefficient of Variation 31 |
| Talazoparib: Severe Hepatic Impairment | Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22 | NA percentage of dose | — |
Secondary
Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1
Ae0-24% was defined as the amount of talazoparib excreted in urine from time 0 to 24 hours expressed as percentage of administered dose.
Time frame: A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1
Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of talazoparib and had at least 1 of the talazoparib PK parameters. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1 | 7.638 percentage of dose | Geometric Coefficient of Variation 79 |
| Talazoparib: Mild Hepatic Impairment | Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1 | 7.070 percentage of dose | Geometric Coefficient of Variation 71 |
| Talazoparib: Moderate Hepatic Impairment | Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1 | 8.582 percentage of dose | Geometric Coefficient of Variation 85 |
| Talazoparib: Severe Hepatic Impairment | Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1 | 4.641 percentage of dose | Geometric Coefficient of Variation 107 |
Secondary
Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22
Ctrough was defined as plasma trough (pre-dose) concentration of talazoparib. Acceptance criteria for Ctrough on Day 15 and Day 22: received 10 consecutive days of dosing immediately before PK sampling day; Sample drawn within 24 +/-2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day. Ctrough on Day 8: received 7 consecutive days of dosing immediately before PK sampling day; sample drawn within 24 +/- 2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day.
Time frame: Pre-dose on Day 8, 15 and 22
Population: Analysis population for this outcome measure included those participants who met acceptance criteria for Ctrough. Here 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 8 | 2.244 nanogram per milliliter | Geometric Coefficient of Variation 22 |
| Talazoparib: Normal Hepatic Function | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 22 | 2.624 nanogram per milliliter | Geometric Coefficient of Variation 28 |
| Talazoparib: Normal Hepatic Function | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 15 | 2.857 nanogram per milliliter | Geometric Coefficient of Variation 39 |
| Talazoparib: Mild Hepatic Impairment | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 8 | 4.807 nanogram per milliliter | Geometric Coefficient of Variation 93 |
| Talazoparib: Mild Hepatic Impairment | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 22 | 3.699 nanogram per milliliter | Geometric Coefficient of Variation 197 |
| Talazoparib: Mild Hepatic Impairment | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 15 | NA nanogram per milliliter | — |
| Talazoparib: Moderate Hepatic Impairment | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 15 | 2.909 nanogram per milliliter | Geometric Coefficient of Variation 3 |
| Talazoparib: Moderate Hepatic Impairment | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 8 | 3.788 nanogram per milliliter | Geometric Coefficient of Variation 80 |
| Talazoparib: Moderate Hepatic Impairment | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 22 | 3.553 nanogram per milliliter | Geometric Coefficient of Variation 8 |
| Talazoparib: Severe Hepatic Impairment | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 8 | 3.329 nanogram per milliliter | Geometric Coefficient of Variation 57 |
| Talazoparib: Severe Hepatic Impairment | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 22 | NA nanogram per milliliter | — |
| Talazoparib: Severe Hepatic Impairment | Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22 | Day 15 | 4.208 nanogram per milliliter | Geometric Coefficient of Variation 86 |
Secondary
Renal Clearance (CLr) of Talazoparib on Day 22
Renal clearance was calculated as cumulative amount of drug excreted in urine during the 24 hours dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to 24 hours post dose (AUC0-24).
Time frame: Ae: Post-dose at any time between 0 to 12, 12 to 24 hrs on Day 22; AUC0-24: Pre-dose (24 hrs +/- 60 minutes from previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, any time between 8 to12, 24 hrs post-dose on Day 22
Population: PK evaluable analysis population was analyzed. Here, Overall Number of Participants Analyzed =participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Renal Clearance (CLr) of Talazoparib on Day 22 | 1.993 liters per hour | Geometric Coefficient of Variation 57 |
| Talazoparib: Mild Hepatic Impairment | Renal Clearance (CLr) of Talazoparib on Day 22 | 1.449 liters per hour | Geometric Coefficient of Variation 92 |
| Talazoparib: Moderate Hepatic Impairment | Renal Clearance (CLr) of Talazoparib on Day 22 | 1.510 liters per hour | Geometric Coefficient of Variation 39 |
| Talazoparib: Severe Hepatic Impairment | Renal Clearance (CLr) of Talazoparib on Day 22 | NA liters per hour | — |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of talazoparib and had at least 1 of the talazoparib PK parameters. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib: Normal Hepatic Function | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1 | 1.00 hour |
| Talazoparib: Mild Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1 | 1.51 hour |
| Talazoparib: Moderate Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1 | 0.55 hour |
| Talazoparib: Severe Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1 | 1.00 hour |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Population: PK evaluable analysis population included all enrolled participants who completed Day 22 visit, missed less than 5 consecutive doses, received at least 10 consecutive days of 0.5 mg talazoparib daily dose immediately preceding Day 22 visit without dose interruption, not vomited talazoparib dose on Day 1 and last day of dose, at least 85% of total plasma PK samples collection was reported and provided at least 1 of talazoparib PK parameters of primary interest from Day 22 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib: Normal Hepatic Function | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22 | 1.50 hour |
| Talazoparib: Mild Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22 | 2.13 hour |
| Talazoparib: Moderate Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22 | 1.05 hour |
| Talazoparib: Severe Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22 | NA hour |
Secondary
Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22
Clearance of unbound talazoparib is a measure of the rate at which unbound talazoparib is metabolized or eliminated by normal biological processes.
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Population: PK evaluable analysis population included all enrolled participants who completed Day 22 visit, missed less than 5 consecutive doses, received at least 10 consecutive days of 0.5 mg talazoparib daily dose immediately preceding Day 22 visit without dose interruption, not vomited talazoparib dose on Day 1 and last day of dose, at least 85% of total plasma PK samples collection was reported and provided at least 1 of talazoparib PK parameters of primary interest from Day 22 visit.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22 | 16.57 liter per hour | Geometric Coefficient of Variation 11 |
| Talazoparib: Mild Hepatic Impairment | Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22 | 11.09 liter per hour | Geometric Coefficient of Variation 84 |
| Talazoparib: Moderate Hepatic Impairment | Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22 | 14.92 liter per hour | Geometric Coefficient of Variation 35 |
| Talazoparib: Severe Hepatic Impairment | Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22 | NA liter per hour | — |
Secondary
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1
AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu\*AUC0-24.
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of talazoparib and had at least 1 of the talazoparib PK parameters. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1 | 6.388 nanogram*hour per milliliter | Geometric Coefficient of Variation 42 |
| Talazoparib: Mild Hepatic Impairment | Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1 | 7.569 nanogram*hour per milliliter | Geometric Coefficient of Variation 35 |
| Talazoparib: Moderate Hepatic Impairment | Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1 | 6.922 nanogram*hour per milliliter | Geometric Coefficient of Variation 14 |
| Talazoparib: Severe Hepatic Impairment | Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1 | 7.528 nanogram*hour per milliliter | Geometric Coefficient of Variation 51 |
Comparison: AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.90% CI: [83.81, 167.47]
Comparison: AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.90% CI: [73.25, 160.3]
Comparison: AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.90% CI: [85.29, 162.83]
Secondary
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu\*Cmax
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of talazoparib and had at least 1 of the talazoparib PK parameters. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1 | 0.8823 nanogram per milliliter | Geometric Coefficient of Variation 76 |
| Talazoparib: Mild Hepatic Impairment | Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1 | 0.8345 nanogram per milliliter | Geometric Coefficient of Variation 35 |
| Talazoparib: Moderate Hepatic Impairment | Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1 | 0.8131 nanogram per milliliter | Geometric Coefficient of Variation 40 |
| Talazoparib: Severe Hepatic Impairment | Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1 | 0.7448 nanogram per milliliter | Geometric Coefficient of Variation 78 |
Comparison: Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [51.69, 164.26]
Comparison: Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [56.74, 157.64]
Comparison: Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.90% CI: [53.14, 134.1]
Other Pre-specified
Number of Participants With TEAEs Leading to Study Drug Discontinuation
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs leading to study drug discontinuation are reported.
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis set included all participants who received any amount of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib: Normal Hepatic Function | Number of Participants With TEAEs Leading to Study Drug Discontinuation | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With TEAEs Leading to Study Drug Discontinuation | 2 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With TEAEs Leading to Study Drug Discontinuation | 2 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With TEAEs Leading to Study Drug Discontinuation | 12 Participants |
Other Pre-specified
Number of Participants With TEAEs Resulting in Death
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs resulting in death are reported.
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis set included all participants who received any amount of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib: Normal Hepatic Function | Number of Participants With TEAEs Resulting in Death | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With TEAEs Resulting in Death | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With TEAEs Resulting in Death | 1 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With TEAEs Resulting in Death | 7 Participants |
Other Pre-specified
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. TEAEs were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs.
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis set included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 6 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 3 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 8 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 14 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 13 Participants |
Other Pre-specified
Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs
A treatment-related adverse event was any untoward medical occurrence attributed to talazoparib in a participant who received talazoparib. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; Congenital anomaly. Relatedness to talazoparib was assessed by the investigator.
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Population: Safety analysis set included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib: Normal Hepatic Function | Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs | AEs | 4 Participants |
| Talazoparib: Normal Hepatic Function | Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs | SAEs | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs | SAEs | 0 Participants |
| Talazoparib: Mild Hepatic Impairment | Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs | AEs | 3 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs | AEs | 0 Participants |
| Talazoparib: Moderate Hepatic Impairment | Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs | SAEs | 0 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs | AEs | 2 Participants |
| Talazoparib: Severe Hepatic Impairment | Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs | SAEs | 0 Participants |