An Open-Label Pharmacokinetics and Safety Study of Talazo... | NCT02997176 | Trialant
NCT02997176
Sponsor
Pfizer
Status
Completed
Last Update Posted
Feb 25, 2021Actual
Enrollment
38Actual
Phase
Phase 1
Conditions
Advanced Solid Tumors
Interventions
Talazoparib
Countries
United States
Protocol Section
Identification Module
NCT ID
Results Section
Participant Flow Module
Pre-assignment Details
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Derived Section
Miscellaneous Info Module
Version Holder
NCT02997176
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
MDV3800-02
Secondary IDs
ID
Type
Description
Link
C3441002
Other Identifier
Alias Study Number
Brief Title
An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800)
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
Acronym
Not provided
Organization
PfizerINDUSTRY
Status Module
Record Verification Date
Feb 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Sep 30, 2016Actual
Primary Completion Date
Feb 12, 2020Actual
Completion Date
Feb 12, 2020Actual
First Submitted Date
Dec 15, 2016
First Submission Date that Met QC Criteria
Dec 15, 2016
First Posted Date
Dec 19, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Feb 5, 2021
Results First Submitted that Met QC Criteria
Feb 5, 2021
Results First Posted Date
Feb 25, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 5, 2021
Last Update Posted Date
Feb 25, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
PfizerINDUSTRY
Collaborators
Name
Class
Medivation, Inc.
INDUSTRY
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
This is a trial to investigate the pharmacokinetics (PK) and the safety of talazoparib in patients with advanced solid tumors and impaired hepatic function.
Detailed Description
At the end of the study, patients with no clinically significant toxicities, no contraindications to continue treatment with talazoparib, and no disease progression (underlying cancer progression) may be eligible to continue talazoparib treatment in a separate open-label extension study. The decision to allow the patient to continue dosing with talazoparib in an open-label extension (OLE) study will be based on potential overall benefit-risk and patient meeting eligibility criteria for OLE.
Conditions Module
Conditions
Advanced Solid Tumors
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
38Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Group A (control, normal hepatic function)
Experimental
Drug: Talazoparib
Group B (mild hepatic dysfunction)
Experimental
Drug: Talazoparib
Group C (moderate hepatic dysfunction)
Experimental
Drug: Talazoparib
Group D (severe hepatic dysfunction)
Experimental
Drug: Talazoparib
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Talazoparib
Drug
Daily oral doses of talazoparib 0.5 mg
Group A (control, normal hepatic function)
Group B (mild hepatic dysfunction)
Group C (moderate hepatic dysfunction)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
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
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22
Cmax was defined as the maximum observed plasma concentration of talazoparib.
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
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22
AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu*AUC0-24. fu= Fraction of Unbound (fu) Plasma.
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
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu*Cmax.
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
Secondary Outcomes
Measure
Description
Time Frame
Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
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
Other Outcomes
Measure
Description
Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. TEAEs were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs.
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Signed and dated Informed Consent Form (by the patient or a legally acceptable representative as per the local regulations).
Female or male at least 18 years of age.
Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator
Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
Expected life expectancy of ≥ 3 months.
Able to swallow the study drug (no contraindication to oral agents).
Hepatic function at screening and enrollment as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria.
Adequate other organ function at screening and enrollment.
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.
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.
Female patients must not be breastfeeding at screening nor during the study participation until 7 months after the last dose of the study drug.
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Exclusion Criteria:
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
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.
Major surgery within 28 days prior to enrollment.
Serious accompanying cardiac disorder
Active known or suspected brain metastasis or active leptomeningeal disease needing treatment
Symptomatic or impending spinal cord compression or cauda equine syndrome
Has undergone a liver transplant, kidney transplant or nephrectomy.
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.
Known myelodysplastic syndrome
Seropositive for human immunodeficiency virus (HIV).
Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
Gastrointestinal disorder affecting absorption.
Known or suspected hypersensitivity to any of the talazoparib capsule components.
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
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Pfizer Pfizer CT.gov Call Center
Pfizer
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
UCLA Hematology/Oncology - Alhambra
Alhambra
California
91801
United States
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
References Module
Citations
Not provided
See Also Links
Label
URL
To obtain contact information for a study center near you, click here.
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
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.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Talazoparib: Normal Hepatic Function
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.
FG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
FG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
FG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
FG0007 subjects
FG00110 subjects
FG0025 subjects
FG00316 subjects
COMPLETED
FG0006 subjects
FG0018 subjects
FG0023 subjects
FG0035 subjects
NOT COMPLETED
FG0001 subjects
FG0012 subjects
FG0022 subjects
FG00311 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Baseline Characteristics Module
Baseline Analysis Population Description
Safety analysis set included all participants who received any amount of talazoparib.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
BG001
Talazoparib: Mild Hepatic Impairment
Denominators
Units
Counts
Participants
BG000
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Outcome Measures Module
Outcome Measures
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hour per milliliter
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
ID
Title
Description
OG000
Adverse Events Module
Frequency Threshold
0
Time Frame
Baseline up to 30 days after last dose of study drug (up to 52 days)
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.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1
Cmax was defined as the maximum observed plasma concentration of talazoparib.
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
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
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 (fu) Plasma Talazoparib on Day 1
Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%).
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
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1
AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu*AUC0-24.
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
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu*Cmax
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
Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22
Ctrough was defined as plasma trough (pre-dose) concentration of talazoparib. Acceptance criteria for Ctrough on Day 15 and Day 22: received 10 consecutive days of dosing immediately before PK sampling day; Sample drawn within 24 +/-2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day. Ctrough on Day 8: received 7 consecutive days of dosing immediately before PK sampling day; sample drawn within 24 +/- 2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day.
Pre-dose on Day 8, 15 and 22
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
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 (fu) Plasma Talazoparib on Day 22
Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%).
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
Accumulation Ratio (Rac) of Plasma Talazoparib
Accumulation ratio for AUC0-24 was calculated as area under the curve from time zero to 24 hours on Day 22 divided by area under the curve from time zero to 24 hours on Day 1.
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
Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22
Talazoparib clearance is a measure of the rate at which talazoparib is metabolized or eliminated by normal biological processes.
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
Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22
Clearance of unbound talazoparib is a measure of the rate at which unbound talazoparib is metabolized or eliminated by normal biological processes.
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
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1
Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose.
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
Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1
Ae0-24% was defined as the amount of talazoparib excreted in urine from time 0 to 24 hours expressed as percentage of administered dose.
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
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22
Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose.
Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 22
Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22
Ae 0-24% was defined as the amount of talazoparib excreted in urine from time 0 to 24 hours expressed as percentage of administered dose.
Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours (hrs) on Day 22
Renal Clearance (CLr) of Talazoparib on Day 22
Renal clearance was calculated as cumulative amount of drug excreted in urine during the 24 hours dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to 24 hours post dose (AUC0-24).
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
Number of Participants With Clinically Significant Laboratory Abnormalities
Clinically significant laboratory abnormalities included aspartate transaminase (AST) or alanine aminotransferase (ALT) >=3 times ULN (>5 *ULN if baseline ALT/AST is >3 *ULN) and total bilirubin (TBL) >2 times ULN or INR >1.5, AST or ALT >=3 times ULN with signs and symptoms consistent with hepatitis and/or eosinophilia (>=500 eosinophils/microliter).
Baseline up to 30 days after last dose of study drug (up to 52 days)
Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study
Systolic blood pressure and diastolic blood pressure were evaluated for examination of vital signs.
Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study
Heart rate was measured in beats per minute.
Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study
Respiratory rate was measured in terms of breaths per minute.
Baseline, Day 8, 15, 22 and End of Study (Day 52)
Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study
Baseline, Day 8, 15, 22 and End of Study (Day 52)
Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria
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.
Baseline up to 30 days after last dose of study drug (up to 52 days)
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
As per ECOG, participant's performance status was measured as: 0=fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature, e.g., light housework, office work; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair.
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)
Baseline up to 30 days after last dose of study drug (up to 52 days)
Number of Participants With TEAEs Leading to Study Drug Discontinuation
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs leading to study drug discontinuation are reported.
Baseline up to 30 days after last dose of study drug (up to 52 days)
Number of Participants With TEAEs Resulting in Death
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs resulting in death are reported.
Baseline up to 30 days after last dose of study drug (up to 52 days)
Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs
A treatment-related adverse event was any untoward medical occurrence attributed to talazoparib in a participant who received talazoparib. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; Congenital anomaly. Relatedness to talazoparib was assessed by the investigator.
Baseline up to 30 days after last dose of study drug (up to 52 days)
Bakersfield
California
93309
United States
St. Joseph Heritage Healthcare
Fullerton
California
92835
United States
St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
Fullerton
California
92835
United States
UCLA Hematology/Oncology
Los Angeles
California
90095
United States
UCLA Hematology/Oncology - Porter Ranch
Porter Ranch
California
91326
United States
UCLA Hematology/Oncology - Santa Monica
Santa Monica
California
90404
United States
UCLA Torrance Oncology
Torrance
California
90505
United States
UCLA Hematology/Oncology - Santa Clarita
Valencia
California
91355
United States
Orlando Health, Inc.
Orlando
Florida
32806
United States
The University of Texas MD Anderson Cancer Center
Houston
Texas
77030
United States
8 subjects
Progressive Disease
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
Death
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
Withdrawal by Subject
FG0000 subjects
FG0012 subjects
FG0020 subjects
FG0031 subjects
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.
BG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
BG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
BG004
Total
Total of all reporting groups
7
BG00110
BG0025
BG00316
BG00438
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00060.3± 7.61
BG00156.6± 17.08
BG00260.4± 6.31
BG00352.7± 11.98
BG00456.1± 12.40
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0005
BG0017
BG0025
BG0039
BG00426
Male
BG0002
BG0013
BG0020
BG0037
BG004
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0012
BG0022
BG0031
BG0046
Not Hispanic or Latino
BG0004
BG0017
BG0023
BG00314
BG004
Unknown or Not Reported
BG0002
BG0011
BG0020
BG0031
BG004
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Asian
BG0001
BG0012
BG0020
BG0031
BG0044
White
BG0005
BG0018
BG0025
BG00313
BG004
Other
BG0001
BG0010
BG0020
BG0032
BG004
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0016
OG0023
OG0032
Title
Denominators
Categories
Title
Measurements
OG000111.8± 30
OG001159.0± 99
OG002123.6± 30
OG003NA± NAData is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
AUC0-24 was natural log-transformed and analyzed using an analysis of variance (ANOVA) model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
142.19
2-Sided
90
79.92
252.98
Other
Bioequivalence
OG000
OG002
AUC0-24 was natural log-transformed and analyzed using an analysis of variance (ANOVA) model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
110.54
2-Sided
90
54.58
223.85
Other
Bioequivalence
Primary
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22
Cmax was defined as the maximum observed plasma concentration of talazoparib.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0016
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG00010.30± 23
OG00111.30± 65
OG00213.56± 23
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
109.76
2-Sided
90
70.93
169.84
Other
Bioequivalence
OG000
OG002
Primary
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22
AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu*AUC0-24. fu= Fraction of Unbound (fu) Plasma.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hour per milliliter
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0016
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG00030.17± 11
OG00145.08± 84
OG00233.50± 35
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
AUC0-24u was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
149.39
2-Sided
90
91.49
243.93
Other
Bioequivalence
OG000
OG002
Primary
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu*Cmax.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0016
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0002.778± 27
OG0013.204± 56
OG0023.675± 28
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
115.32
2-Sided
90
77.95
170.6
Other
Bioequivalence
OG000
OG002
Secondary
Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hour per milliliter
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG0018
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG00022.21± 41
OG00127.63± 38
OG00225.20± 7
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
124.40
2-Sided
90
85.19
181.66
Other
Bioequivalence
OG000
OG002
Secondary
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1
Cmax was defined as the maximum observed plasma concentration of talazoparib.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG0018
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG0003.068± 66
OG0013.047± 32
OG0022.959± 44
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
99.31
2-Sided
90
57.74
170.80
Other
Bioequivalence
OG000
OG002
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
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.
Posted
Median
Full Range
hour
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG0018
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.00(0.50 to 1.02)
OG0011.51(0.50 to 2.05)
OG0020.55(0.48 to 1.02)
OG003
Secondary
Fraction of Unbound (fu) Plasma Talazoparib on Day 1
Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%).
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
percentage of drug concentration
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG0019
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG00028.76± 20
OG00128.11± 14
OG00227.47± 15
OG003
Secondary
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1
AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu*AUC0-24.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hour per milliliter
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG0018
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG0006.388± 42
OG0017.569± 35
OG0026.922± 14
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
118.47
2-Sided
90
83.81
167.47
Other
Bioequivalence
OG000
OG002
Secondary
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu*Cmax
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG0018
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.8823± 76
OG0010.8345± 35
OG0020.8131± 40
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
94.58
2-Sided
90
56.74
157.64
Other
Bioequivalence
OG000
OG002
Secondary
Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22
Ctrough was defined as plasma trough (pre-dose) concentration of talazoparib. Acceptance criteria for Ctrough on Day 15 and Day 22: received 10 consecutive days of dosing immediately before PK sampling day; Sample drawn within 24 +/-2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day. Ctrough on Day 8: received 7 consecutive days of dosing immediately before PK sampling day; sample drawn within 24 +/- 2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter
Pre-dose on Day 8, 15 and 22
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0016
OG0025
OG003
Title
Denominators
Categories
Day 8
ParticipantsOG0005
ParticipantsOG0016
ParticipantsOG0025
ParticipantsOG003
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
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.
Posted
Median
Full Range
hour
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0016
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.50(0.50 to 2.13)
OG0012.13(1.05 to 4.00)
OG0021.05(1.00 to 2.75)
OG003
Secondary
Fraction of Unbound (fu) Plasma Talazoparib on Day 22
Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%).
Analysis population included participants with available data.
Posted
Geometric Mean
Geometric Coefficient of Variation
percentage of drug concentration
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0018
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG00026.98± 23
OG00127.71± 18
OG00227.10± 9
OG003
Secondary
Accumulation Ratio (Rac) of Plasma Talazoparib
Accumulation ratio for AUC0-24 was calculated as area under the curve from time zero to 24 hours on Day 22 divided by area under the curve from time zero to 24 hours on Day 1.
PK evaluable analysis population was analyzed. Here, "Overall Number of Participants Analyzed" =participants evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ratio
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0015
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0005.070± 24
OG0015.134± 68
OG0024.771± 31
OG003
Secondary
Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22
Talazoparib clearance is a measure of the rate at which talazoparib is metabolized or eliminated by normal biological processes.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
liter per hour
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0016
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0005.070± 24
OG0015.134± 68
OG0024.771± 31
OG003
Secondary
Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22
Clearance of unbound talazoparib is a measure of the rate at which unbound talazoparib is metabolized or eliminated by normal biological processes.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
liter per hour
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0016
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG00016.57± 11
OG00111.09± 84
OG00214.92± 35
OG003
Secondary
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1
Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
milligram
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG0018
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.03816± 79
OG0010.03534± 71
OG0020.04292± 85
OG003
Secondary
Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1
Ae0-24% was defined as the amount of talazoparib excreted in urine from time 0 to 24 hours expressed as percentage of administered dose.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
percentage of dose
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG0018
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG0007.638± 79
OG0017.070± 71
OG0028.582± 85
OG003
Secondary
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22
Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose.
PK evaluable analysis population was analyzed. Here, "Overall Number of Participants Analyzed" =participants evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
milligram
Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 22
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0015
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.2229± 30
OG0010.1819± 34
OG0020.1867± 32
OG003
Secondary
Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22
Ae 0-24% was defined as the amount of talazoparib excreted in urine from time 0 to 24 hours expressed as percentage of administered dose.
PK evaluable analysis population was analyzed. Here, "Overall Number of Participants Analyzed" =participants evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
percentage of dose
Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours (hrs) on Day 22
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0015
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG00044.58± 30
OG00136.36± 34
OG00237.40± 31
OG003
Secondary
Renal Clearance (CLr) of Talazoparib on Day 22
Renal clearance was calculated as cumulative amount of drug excreted in urine during the 24 hours dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to 24 hours post dose (AUC0-24).
PK evaluable analysis population was analyzed. Here, "Overall Number of Participants Analyzed" =participants evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
liters per hour
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
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0006
OG0015
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.993± 57
OG0011.449± 92
OG0021.510± 39
OG003
Other Pre-specified
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. TEAEs were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs.
Safety analysis set included all participants who received any amount of talazoparib.
Posted
Count of Participants
Participants
Baseline up to 30 days after last dose of study drug (up to 52 days)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
TEAEs
Title
Measurements
OG0006
OG0018
OG0023
OG003
Other Pre-specified
Number of Participants With TEAEs Leading to Study Drug Discontinuation
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs leading to study drug discontinuation are reported.
Safety analysis set included all participants who received any amount of talazoparib.
Posted
Count of Participants
Participants
Baseline up to 30 days after last dose of study drug (up to 52 days)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0012
OG0022
OG003
Other Pre-specified
Number of Participants With TEAEs Resulting in Death
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs resulting in death are reported.
Safety analysis set included all participants who received any amount of talazoparib.
Posted
Count of Participants
Participants
Baseline up to 30 days after last dose of study drug (up to 52 days)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0021
OG003
Other Pre-specified
Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs
A treatment-related adverse event was any untoward medical occurrence attributed to talazoparib in a participant who received talazoparib. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; Congenital anomaly. Relatedness to talazoparib was assessed by the investigator.
Safety analysis set included all participants who received any amount of talazoparib.
Posted
Count of Participants
Participants
Baseline up to 30 days after last dose of study drug (up to 52 days)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
AEs
Title
Measurements
OG0004
OG0013
OG0020
OG003
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities
Clinically significant laboratory abnormalities included aspartate transaminase (AST) or alanine aminotransferase (ALT) >=3 times ULN (>5 *ULN if baseline ALT/AST is >3 *ULN) and total bilirubin (TBL) >2 times ULN or INR >1.5, AST or ALT >=3 times ULN with signs and symptoms consistent with hepatitis and/or eosinophilia (>=500 eosinophils/microliter).
Safety analysis set included all participants who received any amount of talazoparib.
Posted
Count of Participants
Participants
Baseline up to 30 days after last dose of study drug (up to 52 days)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Secondary
Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study
Systolic blood pressure and diastolic blood pressure were evaluated for examination of vital signs.
Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
Posted
Mean
Standard Deviation
millimeter of mercury (mmHg)
Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
Systolic Blood Pressure: Baseline
ParticipantsOG0007
ParticipantsOG00110
ParticipantsOG0025
ParticipantsOG003
Secondary
Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study
Heart rate was measured in beats per minute.
Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
Posted
Mean
Standard Deviation
beats per minute
Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
Baseline
ParticipantsOG0007
ParticipantsOG00110
ParticipantsOG0025
ParticipantsOG003
Secondary
Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study
Respiratory rate was measured in terms of breaths per minute.
Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
Posted
Mean
Standard Deviation
breaths per minute
Baseline, Day 8, 15, 22 and End of Study (Day 52)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
Baseline
ParticipantsOG0007
ParticipantsOG00110
ParticipantsOG0025
ParticipantsOG003
Secondary
Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study
Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
Posted
Mean
Standard Deviation
kilogram
Baseline, Day 8, 15, 22 and End of Study (Day 52)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
Baseline
ParticipantsOG0007
ParticipantsOG00110
ParticipantsOG0025
ParticipantsOG003
Secondary
Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria
Pre-specified 12-Lead electrocardiogram (ECG) Criteria: QTCF (Fridericia's correction formula) : >=450 to <480 milliseconds, >=480 to <500 milliseconds, >=500 milliseconds, increase from baseline >=30 - <60, increase from baseline >=60, PR interval: >=300 milliseconds, increase from baseline >=25%; QRS duration: >=140 milliseconds, increase from baseline >=50%; QT interval: >=500 milliseconds; QT Interval: >= 500 milliseconds.
Safety analysis set included all participants who received any amount of talazoparib.
Posted
Count of Participants
Participants
Baseline up to 30 days after last dose of study drug (up to 52 days)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
QTCF: >=450 - <480 milliseconds
Title
Measurements
OG0002
OG0012
OG0021
OG003
Secondary
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
As per ECOG, participant's performance status was measured as: 0=fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature, e.g., light housework, office work; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair.
Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.
Posted
Count of Participants
Participants
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)
ID
Title
Description
OG000
Talazoparib: Normal Hepatic Function
Participants with TB and AST <=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
OG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
OG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
Units
Counts
Participants
OG0007
OG00110
OG0025
OG003
Title
Denominators
Categories
Screening
ParticipantsOG0007
ParticipantsOG00110
ParticipantsOG0025
ParticipantsOG003
0
7
1
7
6
7
EG001
Talazoparib: Mild Hepatic Impairment
Participants with TB <=ULN and AST greater than (>) ULN or TB >1.0 to 1.5* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
0
10
3
10
7
10
EG002
Talazoparib: Moderate Hepatic Impairment
Participants with TB >1.5 to 3.0 *ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
1
5
2
5
3
5
EG003
Talazoparib: Severe Hepatic Impairment
Participants with TB >3*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.
7
16
13
16
10
16
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0034 affected16 at risk
Pyrexia
General disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0021 affected5 at risk
EG0032 affected16 at risk
Cholangitis
Hepatobiliary disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0033 affected16 at risk
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Neoplasm progression
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0021 affected5 at risk
EG0032 affected16 at risk
Malignant pleural effusion
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Abdominal pain
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Ascites
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Intestinal obstruction
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Nausea
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Hepatic encephalopathy
Nervous system disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Facial paralysis
Nervous system disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Leukocytosis
Blood and lymphatic system disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Cardio-respiratory arrest
Cardiac disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Coronary artery occlusion
Cardiac disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
EG0004 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0021 affected5 at risk
EG0031 affected16 at risk
Nausea
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0002 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0012 affected10 at risk
EG0020 affected5 at risk
EG0033 affected16 at risk
Abdominal pain
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Diarrhoea
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0002 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Anaemia
Blood and lymphatic system disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Hepatic encephalopathy
Nervous system disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Vomiting
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Ascites
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Coagulopathy
Blood and lymphatic system disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Constipation
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0002 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Headache
Nervous system disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Oedema peripheral
General disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Sepsis
Infections and infestations
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0032 affected16 at risk
Breast pain
Reproductive system and breast disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Chills
General disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Decreased appetite
Metabolism and nutrition disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Dizziness
Nervous system disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Ear pain
Ear and labyrinth disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Toothache
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Urinary tract infection
Infections and infestations
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Pelvic pain
Reproductive system and breast disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Pyrexia
General disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Upper respiratory tract infection
Infections and infestations
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Oesophagitis
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0021 affected5 at risk
EG0030 affected16 at risk
Device related infection
Infections and infestations
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0021 affected5 at risk
EG0030 affected16 at risk
Colitis
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0021 affected5 at risk
EG0030 affected16 at risk
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0021 affected5 at risk
EG0030 affected16 at risk
Abdominal distension
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Ammonia increased
Investigations
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Cholangitis
Hepatobiliary disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Device occlusion
Product Issues
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Generalised oedema
General disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Haematochezia
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Haematoma
Vascular disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Hepatosplenomegaly
Hepatobiliary disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Petechiae
Skin and subcutaneous tissue disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
Night sweats
Skin and subcutaneous tissue disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0030 affected16 at risk
Abdominal pain upper
Gastrointestinal disorders
MedDRA (v23.0)
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected10 at risk
EG0020 affected5 at risk
EG0031 affected16 at risk
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
12
28
4
31
3
2
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
131.67
2-Sided
90
77.14
224.74
Other
Bioequivalence
2
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
AUC0-24u was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
111.04
2-Sided
90
60.91
202.43
Other
Bioequivalence
2
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
132.26
2-Sided
90
81.87
213.67
Other
Bioequivalence
13
21.26
± 58
AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
113.42
2-Sided
90
73.90
174.07
Other
Bioequivalence
OG000
OG003
AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
95.68
2-Sided
90
67.90
134.83
Other
Bioequivalence
15
1.965
± 90
Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
96.45
2-Sided
90
52.22
178.14
Other
Bioequivalence
OG000
OG003
Cmax was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
64.05
2-Sided
90
39.65
103.46
Other
Bioequivalence
15
1.00
(0.50 to 24.62)
14
34.66
± 17
11
7.528
± 51
AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
108.36
2-Sided
90
73.25
160.30
Other
Bioequivalence
OG000
OG003
AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
117.84
2-Sided
90
85.29
162.83
Other
Bioequivalence
13
0.7448
± 78
Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
92.15
2-Sided
90
51.69
164.26
Other
Bioequivalence
OG000
OG003
Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.
Percent Ratio of Geometric Means
84.42
2-Sided
90
53.14
134.10
Other
Bioequivalence
4
4
Title
Measurements
OG0002.244± 22
OG0014.807± 93
OG0023.788± 80
OG0033.329± 57
Day 15
ParticipantsOG0006
ParticipantsOG0012
ParticipantsOG0023
ParticipantsOG0034
Title
Measurements
OG0002.857± 39
OG001NA± NAData is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
OG0022.909± 3
OG003
Day 22
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG0023
ParticipantsOG0032
Title
Measurements
OG0002.624± 28
OG0013.699± 197
OG0023.553± 8
OG003
2
NA
(NA to NA)
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
5
33.92
± 25
1
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
2
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
2
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
8
0.02319
± 107
8
4.641
± 107
2
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
2
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
2
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.
16
14
SAEs
Title
Measurements
OG0001
OG0013
OG0022
OG00313
16
12
16
7
16
2
SAEs
Title
Measurements
OG0000
OG0010
OG0020
OG0030
16
3
16
16
Title
Measurements
OG000128.1± 19.22
OG001110.3± 11.84
OG002121.8± 23.15
OG003115.8± 13.57
Systolic Blood Pressure: Change at Day 2
ParticipantsOG0007
ParticipantsOG0017
ParticipantsOG0024
ParticipantsOG00313
Title
Measurements
OG000-12.3± 17.72
OG001-1.1± 12.86
OG002-12.5± 14.48
OG003
Systolic Blood Pressure: Change at Day 8
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0025
ParticipantsOG00312
Title
Measurements
OG000-2.0± 20.22
OG001-2.8± 9.85
OG002-5.6± 11.97
OG003
Systolic Blood Pressure: Change at Day 15
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0024
ParticipantsOG0038
Title
Measurements
OG000-8.4± 8.64
OG0010.3± 12.08
OG002-6.0± 23.47
OG003
Systolic Blood Pressure: Change at Day 22
ParticipantsOG0006
ParticipantsOG0018
ParticipantsOG0023
ParticipantsOG0039
Title
Measurements
OG000-7.5± 15.10
OG001-4.3± 14.30
OG002-10.7± 32.56
OG003
Systolic Blood Pressure: Change at end of study (Day 52)
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0020
ParticipantsOG0031
Title
Measurements
OG000-0.8± 18.36
OG0010.7± 14.22
OG003-26.0
Diastolic Blood Pressure: Baseline
ParticipantsOG0007
ParticipantsOG00110
ParticipantsOG0025
ParticipantsOG00316
Title
Measurements
OG00075.9± 12.52
OG00165.9± 10.77
OG00268.4± 5.59
OG003
Diastolic Blood Pressure: Change at Day 2
ParticipantsOG0007
ParticipantsOG0017
ParticipantsOG0024
ParticipantsOG00313
Title
Measurements
OG000-5.0± 6.76
OG0014.1± 7.69
OG002-4.5± 6.19
OG003
Diastolic Blood Pressure: Change at Day 8
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0025
ParticipantsOG00312
Title
Measurements
OG000-1.0± 12.04
OG0014.1± 6.66
OG002-0.8± 9.12
OG003
Diastolic Blood Pressure: Change at Day 15
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0024
ParticipantsOG0038
Title
Measurements
OG000-1.4± 6.92
OG0010.9± 9.00
OG0020.8± 10.84
OG003
Diastolic Blood Pressure: Change at Day 22
ParticipantsOG0006
ParticipantsOG0018
ParticipantsOG0023
ParticipantsOG0039
Title
Measurements
OG000-3.5± 9.14
OG001-3.0± 7.82
OG002-3.3± 15.53
OG003
Diastolic Blood Pressure: Change at end of study (Day 52)
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0020
ParticipantsOG0031
Title
Measurements
OG000-0.3± 8.26
OG0011.9± 7.52
OG003-17.0
16
16
Title
Measurements
OG00075.9± 7.67
OG00189.2± 19.34
OG00287.4± 22.13
OG00392.3± 16.76
Change at Day 2
ParticipantsOG0007
ParticipantsOG0017
ParticipantsOG0024
ParticipantsOG00313
Title
Measurements
OG0003.0± 7.64
OG0014.7± 10.01
OG0021.0± 6.16
OG003
Change at Day 8
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0025
ParticipantsOG00312
Title
Measurements
OG0001.7± 7.78
OG0013.5± 16.10
OG0021.6± 4.67
OG003
Change at Day 15
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0024
ParticipantsOG0038
Title
Measurements
OG0005.1± 9.82
OG001-6.0± 12.76
OG0022.5± 7.05
OG003
Change at Day 22
ParticipantsOG0006
ParticipantsOG0018
ParticipantsOG0023
ParticipantsOG0039
Title
Measurements
OG0002.2± 9.81
OG001-9.9± 20.38
OG002-2.0± 1.00
OG003
Change at end of study (Day 52)
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0020
ParticipantsOG0031
Title
Measurements
OG0008.5± 11.90
OG0013.1± 15.56
OG00323.0
16
16
Title
Measurements
OG00018.3± 2.63
OG00117.1± 1.20
OG00216.8± 0.84
OG00317.4± 1.63
Change at Day 8
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0025
ParticipantsOG00312
Title
Measurements
OG000-0.3± 2.06
OG0010.6± 1.77
OG0021.2± 2.39
OG003
Change at Day 15
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0023
ParticipantsOG0038
Title
Measurements
OG000-1.6± 3.15
OG001-0.4± 1.51
OG0020.3± 1.53
OG003
Change at Day 22
ParticipantsOG0006
ParticipantsOG0018
ParticipantsOG0023
ParticipantsOG0039
Title
Measurements
OG000-0.2± 0.98
OG001-0.6± 1.41
OG0021.3± 0.58
OG003
Change at end of study (Day 52)
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0020
ParticipantsOG0031
Title
Measurements
OG000-0.5± 1.00
OG0010.1± 1.46
OG0032.0
16
16
Title
Measurements
OG00082.01± 15.749
OG00163.07± 11.493
OG00277.78± 17.070
OG00366.98± 12.979
Change at Day 8
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0025
ParticipantsOG00312
Title
Measurements
OG000-0.04± 0.943
OG001-0.10± 1.865
OG002-2.02± 1.656
OG003
Change at Day 15
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG0024
ParticipantsOG0038
Title
Measurements
OG000-0.36± 0.621
OG001-0.09± 2.119
OG002-1.78± 0.900
OG003
Change at Day 22
ParticipantsOG0006
ParticipantsOG0018
ParticipantsOG0023
ParticipantsOG0039
Title
Measurements
OG000-0.78± 0.546
OG0010.28± 1.647
OG002-1.57± 0.462
OG003
Change at end of study (Day 52)
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0020
ParticipantsOG0031
Title
Measurements
OG0000.48± 1.839
OG0011.81± 1.577
OG0030.90
16
4
QTCF: >=480 - <500 milliseconds
Title
Measurements
OG0000
OG0010
OG0020
OG0031
QTCF: >=500 milliseconds
Title
Measurements
OG0000
OG0010
OG0020
OG0031
QTCF: Increase from baseline >=30 - <60 milliseconds
Title
Measurements
OG0002
OG0010
OG0020
OG0033
QTCF: Increase from baseline >=60 milliseconds
Title
Measurements
OG0000
OG0011
OG0020
OG0031
PR Interval: >=300 milliseconds
Title
Measurements
OG0001
OG0010
OG0020
OG0030
PR Interval: Increase from baseline >=25%
Title
Measurements
OG0001
OG0010
OG0020
OG0032
QRS Duration: >=140 milliseconds
Title
Measurements
OG0000
OG0010
OG0020
OG0031
QRS Duration: Increase from baseline >=50%
Title
Measurements
OG0000
OG0010
OG0020
OG0030
QT Interval: >=500 milliseconds
Title
Measurements
OG0000
OG0010
OG0021
OG0030
16
16
Title
Measurements
ECOG Performance Status: 0
OG0003
OG0011
OG0021
OG0030
ECOG Performance Status: 1
OG0004
OG0018
OG0022
OG00312
ECOG Performance Status: 2
OG0000
OG0011
OG0022
OG0034
ECOG Performance Status: 3
OG0000
OG0010
OG0020
OG0030
ECOG Performance Status: 4
OG0000
OG0010
OG0020
OG0030
Day -1
ParticipantsOG0007
ParticipantsOG00110
ParticipantsOG0024
ParticipantsOG00315
Title
Measurements
ECOG Performance Status: 0
OG0002
OG0010
OG0020
OG003
Safety follow up
ParticipantsOG0004
ParticipantsOG0016
ParticipantsOG0020
ParticipantsOG0031
Title
Measurements
ECOG Performance Status: 0
OG0002
OG0011
OG0020
OG003
4.208
± 86
NA
± NA
Data is not reported, as it was planned to report statistics when there were \>=3 evaluable participants.