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An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800)

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02997176
Collaborator
Medivation, Inc. (Industry)
38
Enrollment
11
Locations
4
Arms
40.4
Actual Duration (Months)
3.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
38 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A PHASE I OPEN-LABEL PHARMACOKINETICS AND SAFETY STUDY OF TALAZOPARIB (MDV3800) IN PATIENTS WITH ADVANCED SOLID TUMORS AND NORMAL OR VARYING DEGREES OF HEPATIC IMPAIRMENT
Actual Study Start Date :
Sep 30, 2016
Actual Primary Completion Date :
Feb 12, 2020
Actual Study Completion Date :
Feb 12, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group A (control, normal hepatic function)

Drug: Talazoparib
Daily oral doses of talazoparib 0.5 mg
Other Names:
  • MDV3800
  • BMN673

    		•
    Experimental: Group B (mild hepatic dysfunction)

    Drug: Talazoparib
    Daily oral doses of talazoparib 0.5 mg
    Other Names:
  • MDV3800
  • BMN673

    		•
    Experimental: Group C (moderate hepatic dysfunction)

    Drug: Talazoparib
    Daily oral doses of talazoparib 0.5 mg
    Other Names:
  • MDV3800
  • BMN673

    		•
    Experimental: Group D (severe hepatic dysfunction)

    Drug: Talazoparib
    Daily oral doses of talazoparib 0.5 mg
    Other Names:
  • MDV3800
  • BMN673

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    Secondary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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 (%).

    5. 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.

    6. 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

    7. 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.

    8. 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.

    9. 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 (%).

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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).

    18. 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).

    19. 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.

    20. 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.

    21. 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.

    22. 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)]

    23. 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.

    24. 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.

    Other Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCLA Hematology/Oncology - Alhambra Alhambra California United States 91801
    2 CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center Bakersfield California United States 93309
    3 St. Joseph Heritage Healthcare Fullerton California United States 92835
    4 St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare Fullerton California United States 92835
    5 UCLA Hematology/Oncology Los Angeles California United States 90095
    6 UCLA Hematology/Oncology - Porter Ranch Porter Ranch California United States 91326
    7 UCLA Hematology/Oncology - Santa Monica Santa Monica California United States 90404
    8 UCLA Torrance Oncology Torrance California United States 90505
    9 UCLA Hematology/Oncology - Santa Clarita Valencia California United States 91355
    10 Orlando Health, Inc. Orlando Florida United States 32806
    11 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Pfizer
    • Medivation, Inc.

    Investigators

    • Study Director: Pfizer Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT02997176
    Other Study ID Numbers:
    • MDV3800-02
    • C3441002
    First Posted:
    Dec 19, 2016
    Last Update Posted:
    Feb 25, 2021
    Last Verified:
    Feb 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Talazoparib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with total bilirubin (TB) and aspartate aminotransferase (AST) less than or equal to (<=) upper limit of normal (ULN), received talazoparib 0.5 milligram (mg) (2 capsules of 0.25 mg), orally once daily for 22 days. 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. 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. 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.
    Period Title: Overall Study
    STARTED 7 10 5 16
    COMPLETED 6 8 3 5
    NOT COMPLETED 1 2 2 11

    Baseline Characteristics

    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment Total
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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. Total of all reporting groups
    Overall Participants 7 10 5 16 38
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60.3
    (7.61)
    56.6
    (17.08)
    60.4
    (6.31)
    52.7
    (11.98)
    56.1
    (12.40)
    Sex: Female, Male (Count of Participants)
    Female
    5
    71.4%
    7
    70%
    5
    100%
    9
    56.3%
    26
    68.4%
    Male
    2
    28.6%
    3
    30%
    0
    0%
    7
    43.8%
    12
    31.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    14.3%
    2
    20%
    2
    40%
    1
    6.3%
    6
    15.8%
    Not Hispanic or Latino
    4
    57.1%
    7
    70%
    3
    60%
    14
    87.5%
    28
    73.7%
    Unknown or Not Reported
    2
    28.6%
    1
    10%
    0
    0%
    1
    6.3%
    4
    10.5%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    1
    14.3%
    2
    20%
    0
    0%
    1
    6.3%
    4
    10.5%
    White
    5
    71.4%
    8
    80%
    5
    100%
    13
    81.3%
    31
    81.6%
    Other
    1
    14.3%
    0
    0%
    0
    0%
    2
    12.5%
    3
    7.9%

    Outcome Measures

    1. Primary Outcome
    Title Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 6 3 2
    Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter]
    111.8
    (30)
    159.0
    (99)
    123.6
    (30)
    NA
    (NA)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Mild Hepatic Impairment
    Comments AUC0-24 was natural log-transformed and analyzed using an analysis of variance (ANOVA) model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 142.19
    Confidence Interval (2-Sided) 90%
    79.92 to 252.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Moderate Hepatic Impairment
    Comments AUC0-24 was natural log-transformed and analyzed using an analysis of variance (ANOVA) model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 110.54
    Confidence Interval (2-Sided) 90%
    54.58 to 223.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 6 3 2
    Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]
    10.30
    (23)
    11.30
    (65)
    13.56
    (23)
    NA
    (NA)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Mild Hepatic Impairment
    Comments Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 109.76
    Confidence Interval (2-Sided) 90%
    70.93 to 169.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Moderate Hepatic Impairment
    Comments Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 131.67
    Confidence Interval (2-Sided) 90%
    77.14 to 224.74
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    Title Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 6 3 2
    Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter]
    30.17
    (11)
    45.08
    (84)
    33.50
    (35)
    NA
    (NA)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Mild Hepatic Impairment
    Comments AUC0-24u was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 149.39
    Confidence Interval (2-Sided) 90%
    91.49 to 243.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Moderate Hepatic Impairment
    Comments AUC0-24u was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 111.04
    Confidence Interval (2-Sided) 90%
    60.91 to 202.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Primary Outcome
    Title Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 6 3 2
    Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]
    2.778
    (27)
    3.204
    (56)
    3.675
    (28)
    NA
    (NA)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Mild Hepatic Impairment
    Comments Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 115.32
    Confidence Interval (2-Sided) 90%
    77.95 to 170.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Moderate Hepatic Impairment
    Comments Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 132.26
    Confidence Interval (2-Sided) 90%
    81.87 to 213.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 8 5 13
    Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter]
    22.21
    (41)
    27.63
    (38)
    25.20
    (7)
    21.26
    (58)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Mild Hepatic Impairment
    Comments AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 124.40
    Confidence Interval (2-Sided) 90%
    85.19 to 181.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Moderate Hepatic Impairment
    Comments AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 113.42
    Confidence Interval (2-Sided) 90%
    73.90 to 174.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Severe Hepatic Impairment
    Comments AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 95.68
    Confidence Interval (2-Sided) 90%
    67.90 to 134.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 8 5 15
    Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]
    3.068
    (66)
    3.047
    (32)
    2.959
    (44)
    1.965
    (90)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Mild Hepatic Impairment
    Comments Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 99.31
    Confidence Interval (2-Sided) 90%
    57.74 to 170.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Moderate Hepatic Impairment
    Comments Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 96.45
    Confidence Interval (2-Sided) 90%
    52.22 to 178.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Severe Hepatic Impairment
    Comments Cmax was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 64.05
    Confidence Interval (2-Sided) 90%
    39.65 to 103.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 8 5 15
    Median (Full Range) [hour]
    1.00
    1.51
    0.55
    1.00
    8. Secondary Outcome
    Title Fraction of Unbound (fu) Plasma Talazoparib on Day 1
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 9 5 14
    Geometric Mean (Geometric Coefficient of Variation) [percentage of drug concentration]
    28.76
    (20)
    28.11
    (14)
    27.47
    (15)
    34.66
    (17)
    9. Secondary Outcome
    Title Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 8 5 11
    Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter]
    6.388
    (42)
    7.569
    (35)
    6.922
    (14)
    7.528
    (51)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Mild Hepatic Impairment
    Comments AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 118.47
    Confidence Interval (2-Sided) 90%
    83.81 to 167.47
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Moderate Hepatic Impairment
    Comments AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 108.36
    Confidence Interval (2-Sided) 90%
    73.25 to 160.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Severe Hepatic Impairment
    Comments AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 117.84
    Confidence Interval (2-Sided) 90%
    85.29 to 162.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 8 5 13
    Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]
    0.8823
    (76)
    0.8345
    (35)
    0.8131
    (40)
    0.7448
    (78)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Mild Hepatic Impairment
    Comments Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 94.58
    Confidence Interval (2-Sided) 90%
    56.74 to 157.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Moderate Hepatic Impairment
    Comments Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 92.15
    Confidence Interval (2-Sided) 90%
    51.69 to 164.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Talazoparib: Normal Hepatic Function, Talazoparib: Severe Hepatic Impairment
    Comments Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
    Type of Statistical Test Other
    Comments Bioequivalence
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent Ratio of Geometric Means
    Estimated Value 84.42
    Confidence Interval (2-Sided) 90%
    53.14 to 134.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 6 5 4
    Day 8
    2.244
    (22)
    4.807
    (93)
    3.788
    (80)
    3.329
    (57)
    Day 15
    2.857
    (39)
    NA
    (NA)
    2.909
    (3)
    4.208
    (86)
    Day 22
    2.624
    (28)
    3.699
    (197)
    3.553
    (8)
    NA
    (NA)
    12. Secondary Outcome
    Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 6 3 2
    Median (Full Range) [hour]
    1.50
    2.13
    1.05
    NA
    13. Secondary Outcome
    Title Fraction of Unbound (fu) Plasma Talazoparib on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Analysis population included participants with available data.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 8 3 5
    Geometric Mean (Geometric Coefficient of Variation) [percentage of drug concentration]
    26.98
    (23)
    27.71
    (18)
    27.10
    (9)
    33.92
    (25)
    14. Secondary Outcome
    Title Accumulation Ratio (Rac) of Plasma Talazoparib
    Description 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

    Outcome Measure Data

    Analysis Population Description
    PK evaluable analysis population was analyzed. Here, "Overall Number of Participants Analyzed" =participants evaluable for this outcome measure.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 5 3 1
    Geometric Mean (Geometric Coefficient of Variation) [ratio]
    5.070
    (24)
    5.134
    (68)
    4.771
    (31)
    NA
    (NA)
    15. Secondary Outcome
    Title Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 6 3 2
    Geometric Mean (Geometric Coefficient of Variation) [liter per hour]
    5.070
    (24)
    5.134
    (68)
    4.771
    (31)
    NA
    (NA)
    16. Secondary Outcome
    Title Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 6 3 2
    Geometric Mean (Geometric Coefficient of Variation) [liter per hour]
    16.57
    (11)
    11.09
    (84)
    14.92
    (35)
    NA
    (NA)
    17. Secondary Outcome
    Title Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 8 4 8
    Geometric Mean (Geometric Coefficient of Variation) [milligram]
    0.03816
    (79)
    0.03534
    (71)
    0.04292
    (85)
    0.02319
    (107)
    18. Secondary Outcome
    Title Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 8 4 8
    Geometric Mean (Geometric Coefficient of Variation) [percentage of dose]
    7.638
    (79)
    7.070
    (71)
    8.582
    (85)
    4.641
    (107)
    19. Secondary Outcome
    Title Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    PK evaluable analysis population was analyzed. Here, "Overall Number of Participants Analyzed" =participants evaluable for this outcome measure.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 5 3 2
    Geometric Mean (Geometric Coefficient of Variation) [milligram]
    0.2229
    (30)
    0.1819
    (34)
    0.1867
    (32)
    NA
    (NA)
    20. Secondary Outcome
    Title Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    PK evaluable analysis population was analyzed. Here, "Overall Number of Participants Analyzed" =participants evaluable for this outcome measure.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 5 3 2
    Geometric Mean (Geometric Coefficient of Variation) [percentage of dose]
    44.58
    (30)
    36.36
    (34)
    37.40
    (31)
    NA
    (NA)
    21. Secondary Outcome
    Title Renal Clearance (CLr) of Talazoparib on Day 22
    Description 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

    Outcome Measure Data

    Analysis Population Description
    PK evaluable analysis population was analyzed. Here, "Overall Number of Participants Analyzed" =participants evaluable for this outcome measure.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 6 5 3 2
    Geometric Mean (Geometric Coefficient of Variation) [liters per hour]
    1.993
    (57)
    1.449
    (92)
    1.510
    (39)
    NA
    (NA)
    22. Other Pre-specified Outcome
    Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    TEAEs
    6
    85.7%
    8
    80%
    3
    60%
    14
    87.5%
    SAEs
    1
    14.3%
    3
    30%
    2
    40%
    13
    81.3%
    23. Other Pre-specified Outcome
    Title Number of Participants With TEAEs Leading to Study Drug Discontinuation
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    Count of Participants [Participants]
    0
    0%
    2
    20%
    2
    40%
    12
    75%
    24. Other Pre-specified Outcome
    Title Number of Participants With TEAEs Resulting in Death
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    Count of Participants [Participants]
    0
    0%
    0
    0%
    1
    20%
    7
    43.8%
    25. Other Pre-specified Outcome
    Title Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    AEs
    4
    57.1%
    3
    30%
    0
    0%
    2
    12.5%
    SAEs
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    26. Secondary Outcome
    Title Number of Participants With Clinically Significant Laboratory Abnormalities
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    3
    18.8%
    27. Secondary Outcome
    Title Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    Systolic Blood Pressure: Baseline
    128.1
    (19.22)
    110.3
    (11.84)
    121.8
    (23.15)
    115.8
    (13.57)
    Systolic Blood Pressure: Change at Day 2
    -12.3
    (17.72)
    -1.1
    (12.86)
    -12.5
    (14.48)
    2.2
    (10.43)
    Systolic Blood Pressure: Change at Day 8
    -2.0
    (20.22)
    -2.8
    (9.85)
    -5.6
    (11.97)
    -5.3
    (10.80)
    Systolic Blood Pressure: Change at Day 15
    -8.4
    (8.64)
    0.3
    (12.08)
    -6.0
    (23.47)
    -2.3
    (13.91)
    Systolic Blood Pressure: Change at Day 22
    -7.5
    (15.10)
    -4.3
    (14.30)
    -10.7
    (32.56)
    -7.8
    (17.20)
    Systolic Blood Pressure: Change at end of study (Day 52)
    -0.8
    (18.36)
    0.7
    (14.22)
    -26.0
    Diastolic Blood Pressure: Baseline
    75.9
    (12.52)
    65.9
    (10.77)
    68.4
    (5.59)
    73.9
    (10.60)
    Diastolic Blood Pressure: Change at Day 2
    -5.0
    (6.76)
    4.1
    (7.69)
    -4.5
    (6.19)
    -0.8
    (7.03)
    Diastolic Blood Pressure: Change at Day 8
    -1.0
    (12.04)
    4.1
    (6.66)
    -0.8
    (9.12)
    -4.1
    (9.91)
    Diastolic Blood Pressure: Change at Day 15
    -1.4
    (6.92)
    0.9
    (9.00)
    0.8
    (10.84)
    -2.1
    (4.97)
    Diastolic Blood Pressure: Change at Day 22
    -3.5
    (9.14)
    -3.0
    (7.82)
    -3.3
    (15.53)
    -6.0
    (11.17)
    Diastolic Blood Pressure: Change at end of study (Day 52)
    -0.3
    (8.26)
    1.9
    (7.52)
    -17.0
    28. Secondary Outcome
    Title Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study
    Description Heart rate was measured in beats per minute.
    Time Frame Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    Baseline
    75.9
    (7.67)
    89.2
    (19.34)
    87.4
    (22.13)
    92.3
    (16.76)
    Change at Day 2
    3.0
    (7.64)
    4.7
    (10.01)
    1.0
    (6.16)
    1.4
    (11.01)
    Change at Day 8
    1.7
    (7.78)
    3.5
    (16.10)
    1.6
    (4.67)
    -2.7
    (8.79)
    Change at Day 15
    5.1
    (9.82)
    -6.0
    (12.76)
    2.5
    (7.05)
    3.8
    (15.52)
    Change at Day 22
    2.2
    (9.81)
    -9.9
    (20.38)
    -2.0
    (1.00)
    2.3
    (19.16)
    Change at end of study (Day 52)
    8.5
    (11.90)
    3.1
    (15.56)
    23.0
    29. Secondary Outcome
    Title Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study
    Description Respiratory rate was measured in terms of breaths per minute.
    Time Frame Baseline, Day 8, 15, 22 and End of Study (Day 52)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    Baseline
    18.3
    (2.63)
    17.1
    (1.20)
    16.8
    (0.84)
    17.4
    (1.63)
    Change at Day 8
    -0.3
    (2.06)
    0.6
    (1.77)
    1.2
    (2.39)
    -0.1
    (2.19)
    Change at Day 15
    -1.6
    (3.15)
    -0.4
    (1.51)
    0.3
    (1.53)
    0.4
    (1.51)
    Change at Day 22
    -0.2
    (0.98)
    -0.6
    (1.41)
    1.3
    (0.58)
    1.1
    (1.17)
    Change at end of study (Day 52)
    -0.5
    (1.00)
    0.1
    (1.46)
    2.0
    30. Secondary Outcome
    Title Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study
    Description
    Time Frame Baseline, Day 8, 15, 22 and End of Study (Day 52)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    Baseline
    82.01
    (15.749)
    63.07
    (11.493)
    77.78
    (17.070)
    66.98
    (12.979)
    Change at Day 8
    -0.04
    (0.943)
    -0.10
    (1.865)
    -2.02
    (1.656)
    -1.50
    (3.728)
    Change at Day 15
    -0.36
    (0.621)
    -0.09
    (2.119)
    -1.78
    (0.900)
    -1.29
    (5.025)
    Change at Day 22
    -0.78
    (0.546)
    0.28
    (1.647)
    -1.57
    (0.462)
    -2.06
    (5.416)
    Change at end of study (Day 52)
    0.48
    (1.839)
    1.81
    (1.577)
    0.90
    31. Secondary Outcome
    Title Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    QTCF: >=450 - <480 milliseconds
    2
    28.6%
    2
    20%
    1
    20%
    4
    25%
    QTCF: >=480 - <500 milliseconds
    0
    0%
    0
    0%
    0
    0%
    1
    6.3%
    QTCF: >=500 milliseconds
    0
    0%
    0
    0%
    0
    0%
    1
    6.3%
    QTCF: Increase from baseline >=30 - <60 milliseconds
    2
    28.6%
    0
    0%
    0
    0%
    3
    18.8%
    QTCF: Increase from baseline >=60 milliseconds
    0
    0%
    1
    10%
    0
    0%
    1
    6.3%
    PR Interval: >=300 milliseconds
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    PR Interval: Increase from baseline >=25%
    1
    14.3%
    0
    0%
    0
    0%
    2
    12.5%
    QRS Duration: >=140 milliseconds
    0
    0%
    0
    0%
    0
    0%
    1
    6.3%
    QRS Duration: Increase from baseline >=50%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    QT Interval: >=500 milliseconds
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    32. Secondary Outcome
    Title Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    Measure Participants 7 10 5 16
    ECOG Performance Status: 0
    3
    42.9%
    1
    10%
    1
    20%
    0
    0%
    ECOG Performance Status: 1
    4
    57.1%
    8
    80%
    2
    40%
    12
    75%
    ECOG Performance Status: 2
    0
    0%
    1
    10%
    2
    40%
    4
    25%
    ECOG Performance Status: 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    ECOG Performance Status: 4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    ECOG Performance Status: 0
    2
    28.6%
    0
    0%
    0
    0%
    0
    0%
    ECOG Performance Status: 1
    5
    71.4%
    9
    90%
    2
    40%
    11
    68.8%
    ECOG Performance Status: 2
    0
    0%
    1
    10%
    2
    40%
    4
    25%
    ECOG Performance Status: 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    ECOG Performance Status: 4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    ECOG Performance Status: 0
    2
    28.6%
    1
    10%
    0
    0%
    0
    0%
    ECOG Performance Status: 1
    2
    28.6%
    4
    40%
    0
    0%
    1
    6.3%
    ECOG Performance Status: 2
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    ECOG Performance Status: 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    ECOG Performance Status: 4
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame Baseline up to 30 days after last dose of study drug (up to 52 days)
    Adverse Event Reporting Description Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
    Arm/Group Title Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Arm/Group Description Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days. 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. 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. 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.
    All Cause Mortality
    Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/7 (0%) 0/10 (0%) 1/5 (20%) 7/16 (43.8%)
    Serious Adverse Events
    Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/7 (14.3%) 3/10 (30%) 2/5 (40%) 13/16 (81.3%)
    Blood and lymphatic system disorders
    Leukocytosis 0/7 (0%) 1/10 (10%) 0/5 (0%) 1/16 (6.3%)
    Cardiac disorders
    Cardio-respiratory arrest 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Coronary artery occlusion 0/7 (0%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/7 (0%) 1/10 (10%) 0/5 (0%) 2/16 (12.5%)
    Ascites 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Intestinal obstruction 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Nausea 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    General disorders
    Disease progression 0/7 (0%) 0/10 (0%) 0/5 (0%) 4/16 (25%)
    Pyrexia 0/7 (0%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/7 (0%) 0/10 (0%) 1/5 (20%) 2/16 (12.5%)
    Cholangitis 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Metabolism and nutrition disorders
    Hyponatraemia 0/7 (0%) 0/10 (0%) 0/5 (0%) 3/16 (18.8%)
    Hyperkalaemia 0/7 (0%) 0/10 (0%) 0/5 (0%) 2/16 (12.5%)
    Hypercalcaemia 0/7 (0%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression 0/7 (0%) 0/10 (0%) 1/5 (20%) 2/16 (12.5%)
    Malignant pleural effusion 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Nervous system disorders
    Hepatic encephalopathy 0/7 (0%) 0/10 (0%) 0/5 (0%) 2/16 (12.5%)
    Facial paralysis 0/7 (0%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Other (Not Including Serious) Adverse Events
    Talazoparib: Normal Hepatic Function Talazoparib: Mild Hepatic Impairment Talazoparib: Moderate Hepatic Impairment Talazoparib: Severe Hepatic Impairment
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/7 (85.7%) 7/10 (70%) 3/5 (60%) 10/16 (62.5%)
    Blood and lymphatic system disorders
    Thrombocytopenia 0/7 (0%) 2/10 (20%) 0/5 (0%) 3/16 (18.8%)
    Anaemia 0/7 (0%) 1/10 (10%) 0/5 (0%) 2/16 (12.5%)
    Coagulopathy 0/7 (0%) 0/10 (0%) 0/5 (0%) 2/16 (12.5%)
    Ear and labyrinth disorders
    Ear pain 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Gastrointestinal disorders
    Nausea 2/7 (28.6%) 1/10 (10%) 0/5 (0%) 1/16 (6.3%)
    Abdominal pain 0/7 (0%) 0/10 (0%) 0/5 (0%) 2/16 (12.5%)
    Diarrhoea 2/7 (28.6%) 1/10 (10%) 0/5 (0%) 1/16 (6.3%)
    Vomiting 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 2/16 (12.5%)
    Ascites 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Constipation 2/7 (28.6%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Toothache 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Oesophagitis 0/7 (0%) 0/10 (0%) 1/5 (20%) 0/16 (0%)
    Colitis 0/7 (0%) 0/10 (0%) 1/5 (20%) 0/16 (0%)
    Gastrooesophageal reflux disease 0/7 (0%) 0/10 (0%) 1/5 (20%) 0/16 (0%)
    Abdominal distension 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Haematochezia 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Abdominal pain upper 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    General disorders
    Fatigue 4/7 (57.1%) 1/10 (10%) 0/5 (0%) 1/16 (6.3%)
    Oedema peripheral 0/7 (0%) 0/10 (0%) 0/5 (0%) 2/16 (12.5%)
    Chills 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Pyrexia 0/7 (0%) 1/10 (10%) 0/5 (0%) 1/16 (6.3%)
    Generalised oedema 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/7 (0%) 0/10 (0%) 0/5 (0%) 2/16 (12.5%)
    Cholangitis 0/7 (0%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Hepatosplenomegaly 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Infections and infestations
    Sepsis 0/7 (0%) 0/10 (0%) 0/5 (0%) 2/16 (12.5%)
    Urinary tract infection 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Upper respiratory tract infection 0/7 (0%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Device related infection 0/7 (0%) 0/10 (0%) 1/5 (20%) 0/16 (0%)
    Investigations
    Ammonia increased 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Metabolism and nutrition disorders
    Hyponatraemia 0/7 (0%) 0/10 (0%) 1/5 (20%) 1/16 (6.3%)
    Decreased appetite 1/7 (14.3%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Hypokalaemia 0/7 (0%) 1/10 (10%) 0/5 (0%) 1/16 (6.3%)
    Hypoalbuminaemia 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Nervous system disorders
    Hepatic encephalopathy 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Headache 0/7 (0%) 0/10 (0%) 0/5 (0%) 2/16 (12.5%)
    Dizziness 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Product Issues
    Device occlusion 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Reproductive system and breast disorders
    Breast pain 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Pelvic pain 0/7 (0%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Dyspnoea 0/7 (0%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Pleural effusion 0/7 (0%) 1/10 (10%) 0/5 (0%) 0/16 (0%)
    Hypoxia 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Skin and subcutaneous tissue disorders
    Dry skin 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Pruritus 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Petechiae 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)
    Night sweats 1/7 (14.3%) 0/10 (0%) 0/5 (0%) 0/16 (0%)
    Vascular disorders
    Haematoma 0/7 (0%) 0/10 (0%) 0/5 (0%) 1/16 (6.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT02997176
    Other Study ID Numbers:
    • MDV3800-02
    • C3441002
    First Posted:
    Dec 19, 2016
    Last Update Posted:
    Feb 25, 2021
    Last Verified:
    Feb 1, 2021