Trial Outcomes & Findings for An Open-Label Pharmacokinetics and Safety Study of Talazoparib (NCT NCT02997163)

NCT ID: NCT02997163

Last Updated: 2021-01-05

Results Overview

AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

34 participants

Primary outcome timeframe

Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

Results posted on

2021-01-05

Participant Flow

Participant milestones

Participant milestones
Measure	Normal Renal Function Participants with normal renal function (estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 90 milliliter per minute per 1.73 square meter \[mL/min/1.73m\^2\]) received 0.5 milligrams (mg) (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment Participants with mild renal function (eGFR \>= 60 and less than or equal to \[\<=\] 89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Overall Study STARTED	9	9	8	8
Overall Study COMPLETED	8	9	8	7
Overall Study NOT COMPLETED	1	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Normal Renal Function Participants with normal renal function (estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 90 milliliter per minute per 1.73 square meter \[mL/min/1.73m\^2\]) received 0.5 milligrams (mg) (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment Participants with mild renal function (eGFR \>= 60 and less than or equal to \[\<=\] 89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Overall Study Adverse Event	1	0	0	1

Baseline Characteristics

An Open-Label Pharmacokinetics and Safety Study of Talazoparib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Total n=34 Participants Total of all reporting groups
Age, Continuous	59.1 years STANDARD_DEVIATION 6.99 • n=5 Participants	65.4 years STANDARD_DEVIATION 9.13 • n=7 Participants	65.3 years STANDARD_DEVIATION 6.45 • n=5 Participants	72.8 years STANDARD_DEVIATION 13.60 • n=4 Participants	65.4 years STANDARD_DEVIATION 10.20 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	22 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	9 Participants n=7 Participants	7 Participants n=5 Participants	8 Participants n=4 Participants	33 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants	29 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

Population: Pharmacokinetic (PK) analysis population included all participants who had at least 1 reportable talazoparib concentration.

AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib	94.88 nanogram*hour per milliliter Geometric Coefficient of Variation 27	106.5 nanogram*hour per milliliter Geometric Coefficient of Variation 40	135.7 nanogram*hour per milliliter Geometric Coefficient of Variation 45	249.8 nanogram*hour per milliliter Geometric Coefficient of Variation 30

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

Cmax was defined as the maximum observed plasma concentration of talazoparib.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib	8.609 nanogram per milliliter Geometric Coefficient of Variation 35	9.568 nanogram per milliliter Geometric Coefficient of Variation 58	11.33 nanogram per milliliter Geometric Coefficient of Variation 45	16.30 nanogram per milliliter Geometric Coefficient of Variation 34

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib	28.33 nanogram*hour per milliliter Geometric Coefficient of Variation 32	33.59 nanogram*hour per milliliter Geometric Coefficient of Variation 31	39.47 nanogram*hour per milliliter Geometric Coefficient of Variation 47	81.17 nanogram*hour per milliliter Geometric Coefficient of Variation 36

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib	2.570 nanogram per milliliter Geometric Coefficient of Variation 42	3.019 nanogram per milliliter Geometric Coefficient of Variation 47	3.295 nanogram per milliliter Geometric Coefficient of Variation 48	5.296 nanogram per milliliter Geometric Coefficient of Variation 30

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=7 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib	17.51 nanogram*hour per milliliter Geometric Coefficient of Variation 59	23.60 nanogram*hour per milliliter Geometric Coefficient of Variation 47	21.96 nanogram*hour per milliliter Geometric Coefficient of Variation 40	29.98 nanogram*hour per milliliter Geometric Coefficient of Variation 25

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

Cmax was defined as the maximum observed plasma concentration of talazoparib.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib	2.133 nanogram per milliliter Geometric Coefficient of Variation 56	2.422 nanogram per milliliter Geometric Coefficient of Variation 29	2.862 nanogram per milliliter Geometric Coefficient of Variation 75	2.624 nanogram per milliliter Geometric Coefficient of Variation 66

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib	1.515 hours Interval 0.5 to 2.0	1.000 hours Interval 0.97 to 2.12	0.9900 hours Interval 0.48 to 2.0	1.830 hours Interval 0.5 to 8.0

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=6 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib	31.74 ratio Geometric Coefficient of Variation 22	33.71 ratio Geometric Coefficient of Variation 14	28.77 ratio Geometric Coefficient of Variation 7	33.91 ratio Geometric Coefficient of Variation 19

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours for unbound talazoparib.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=7 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=6 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib	5.555 nanogram*hour per milliliter Geometric Coefficient of Variation 81	7.956 nanogram*hour per milliliter Geometric Coefficient of Variation 35	6.262 nanogram*hour per milliliter Geometric Coefficient of Variation 39	10.95 nanogram*hour per milliliter Geometric Coefficient of Variation 28

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1

Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=6 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib	0.6772 nanogram per milliliter Geometric Coefficient of Variation 67	0.8168 nanogram per milliliter Geometric Coefficient of Variation 62	0.8229 nanogram per milliliter Geometric Coefficient of Variation 70	1.031 nanogram per milliliter Geometric Coefficient of Variation 43

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib	1.500 hours Interval 0.97 to 4.0	2.000 hours Interval 0.5 to 4.0	1.490 hours Interval 0.47 to 4.02	3.880 hours Interval 0.5 to 8.0

SECONDARY outcome

Timeframe: Predose on Day 22

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

Ctrough was defined as plasma trough (predose) concentration of talazoparib.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib	2.172 nanogram per milliliter Geometric Coefficient of Variation 34	2.680 nanogram per milliliter Geometric Coefficient of Variation 52	3.893 nanogram per milliliter Geometric Coefficient of Variation 45	7.917 nanogram per milliliter Geometric Coefficient of Variation 44

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

Drug clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib	5.270 liters per hour Geometric Coefficient of Variation 27	4.698 liters per hour Geometric Coefficient of Variation 40	3.687 liters per hour Geometric Coefficient of Variation 45	2.000 liters per hour Geometric Coefficient of Variation 30

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 and Day 22

Accumulation ratio for AUC0-24 was calculated as area under the curve from time zero to 24 hours on Day 22 divided by area under the curve from time zero to 24 hours on Day 1.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=7 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24)	5.418 ratio Geometric Coefficient of Variation 59	4.510 ratio Geometric Coefficient of Variation 42	6.239 ratio Geometric Coefficient of Variation 38	8.330 ratio Geometric Coefficient of Variation 36

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib	29.85 ratio Geometric Coefficient of Variation 24	31.54 ratio Geometric Coefficient of Variation 10	29.09 ratio Geometric Coefficient of Variation 9	32.49 ratio Geometric Coefficient of Variation 30

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22

Population: PK analysis population included all participants who had at least 1 reportable talazoparib concentration.

Clearance of unbound drug is a measure of the rate at which unbound drug is metabolized or eliminated by normal biological processes.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib	17.66 liters per hour Geometric Coefficient of Variation 32	14.89 liters per hour Geometric Coefficient of Variation 31	12.68 liters per hour Geometric Coefficient of Variation 47	6.614 liters per hour Geometric Coefficient of Variation 36

SECONDARY outcome

Timeframe: 0 to 24 hours on Day 1

Ae 0-24 is the amount of drug excreted unchanged in urine from time 0 to 24 hours postdose.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=6 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24)	0.05452 milligram Geometric Coefficient of Variation 51	0.05430 milligram Geometric Coefficient of Variation 38	0.02765 milligram Geometric Coefficient of Variation 59	0.01901 milligram Geometric Coefficient of Variation 78

SECONDARY outcome

Timeframe: 0 to 24 hours on Day 1

Ae0-24% was defined as the amount of drug excreted in urine from time 0 to 24 hours expressed as percentage of administered dose.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=6 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1	10.91 percentage of dose Geometric Coefficient of Variation 51	10.85 percentage of dose Geometric Coefficient of Variation 38	5.532 percentage of dose Geometric Coefficient of Variation 59	3.795 percentage of dose Geometric Coefficient of Variation 78

SECONDARY outcome

Timeframe: 0 to 24 hours on Day 22

Ae 0-24 is the amount of drug excreted unchanged in urine from time 0 to 24 hours postdose.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=5 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=7 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%)	0.2584 milligram Geometric Coefficient of Variation 23	0.2321 milligram Geometric Coefficient of Variation 20	0.1637 milligram Geometric Coefficient of Variation 54	0.2005 milligram Geometric Coefficient of Variation 34

SECONDARY outcome

Timeframe: 0 to 24 hours on Day 22

Ae 0-24% was defined as the amount of drug excreted in urine from time 0 to 24 hours, expressed as percentage of administered dose.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=5 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=7 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=7 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22	51.66 percentage of dose Geometric Coefficient of Variation 23	46.40 percentage of dose Geometric Coefficient of Variation 20	32.78 percentage of dose Geometric Coefficient of Variation 54	40.07 percentage of dose Geometric Coefficient of Variation 34

SECONDARY outcome

Timeframe: 0 to 24 hours 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 postdose.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=5 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=7 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=7 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=5 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22	2.738 liters per hour Geometric Coefficient of Variation 37	2.180 liters per hour Geometric Coefficient of Variation 57	1.330 liters per hour Geometric Coefficient of Variation 97	0.7094 liters per hour Geometric Coefficient of Variation 35

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (up to 52 days)

Population: Safety analysis included all participants who received any amount of talazoparib.

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 investigational product and up to 30 days after the last dose of investigational product (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	7 Participants	8 Participants	8 Participants	7 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	1 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (up to 52 days)

Population: Safety analysis included all participants who received any amount of talazoparib.

Physical examination included examination of the general appearance, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Findings were considered to be abnormal based on investigator's decision.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Number of Participants With Abnormalities in Physical Examination	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)

Population: Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Change From Baseline in Systolic Blood Pressure (SBP) of Participants Baseline	115.4 millimeters of mercury (mmHg) Standard Deviation 13.19	124.3 millimeters of mercury (mmHg) Standard Deviation 11.55	123.8 millimeters of mercury (mmHg) Standard Deviation 11.63	133.6 millimeters of mercury (mmHg) Standard Deviation 17.25
Change From Baseline in Systolic Blood Pressure (SBP) of Participants Change at Day 8	9.0 millimeters of mercury (mmHg) Standard Deviation 17.29	-6.7 millimeters of mercury (mmHg) Standard Deviation 18.28	-2.5 millimeters of mercury (mmHg) Standard Deviation 8.50	-7.3 millimeters of mercury (mmHg) Standard Deviation 11.29
Change From Baseline in Systolic Blood Pressure (SBP) of Participants Change at Day 15	1.9 millimeters of mercury (mmHg) Standard Deviation 13.48	-6.8 millimeters of mercury (mmHg) Standard Deviation 7.03	-5.6 millimeters of mercury (mmHg) Standard Deviation 4.87	-2.9 millimeters of mercury (mmHg) Standard Deviation 18.05
Change From Baseline in Systolic Blood Pressure (SBP) of Participants Change at Day 22	7.3 millimeters of mercury (mmHg) Standard Deviation 15.72	-7.3 millimeters of mercury (mmHg) Standard Deviation 12.66	0.1 millimeters of mercury (mmHg) Standard Deviation 7.90	1.0 millimeters of mercury (mmHg) Standard Deviation 12.02
Change From Baseline in Systolic Blood Pressure (SBP) of Participants Change at Day 52	-3.0 millimeters of mercury (mmHg) Standard Deviation NA Standard deviation was not estimable due to 1 participant with SBP.	-42.0 millimeters of mercury (mmHg) Standard Deviation NA Standard deviation was not estimable due to 1 participant with SBP.	4.3 millimeters of mercury (mmHg) Standard Deviation 9.02	-10.8 millimeters of mercury (mmHg) Standard Deviation 18.75

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)

Population: Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Change From Baseline in Diastolic Blood Pressure (DBP) of Participants Baseline	69.8 mmHg Standard Deviation 7.69	78.3 mmHg Standard Deviation 8.38	69.8 mmHg Standard Deviation 5.65	74.8 mmHg Standard Deviation 14.10
Change From Baseline in Diastolic Blood Pressure (DBP) of Participants Change at Day 8	5.4 mmHg Standard Deviation 4.48	-4.6 mmHg Standard Deviation 10.48	2.8 mmHg Standard Deviation 8.15	-3.4 mmHg Standard Deviation 9.96
Change From Baseline in Diastolic Blood Pressure (DBP) of Participants Change at Day 15	-0.2 mmHg Standard Deviation 6.02	-5.9 mmHg Standard Deviation 6.62	0.4 mmHg Standard Deviation 8.86	-1.1 mmHg Standard Deviation 11.37
Change From Baseline in Diastolic Blood Pressure (DBP) of Participants Change at Day 22	3.4 mmHg Standard Deviation 10.50	-4.6 mmHg Standard Deviation 6.13	5.5 mmHg Standard Deviation 11.95	-4.0 mmHg Standard Deviation 8.18
Change From Baseline in Diastolic Blood Pressure (DBP) of Participants Change at Day 52	4.0 mmHg Standard Deviation NA Standard deviation was not estimable due to 1 participant with DBP.	-18.0 mmHg Standard Deviation NA Standard deviation was not estimable due to 1 participant with DBP.	1.0 mmHg Standard Deviation 6.00	-1.0 mmHg Standard Deviation 20.98

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)

Population: Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows.

Heart rate was measured in terms of beats per minute.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Change From Baseline in Heart Rate of Participants Baseline	85.2 beats per minute Standard Deviation 11.23	81.6 beats per minute Standard Deviation 21.86	80.1 beats per minute Standard Deviation 11.54	77.4 beats per minute Standard Deviation 23.34
Change From Baseline in Heart Rate of Participants Change at Day 8	3.3 beats per minute Standard Deviation 9.18	-0.2 beats per minute Standard Deviation 8.74	2.1 beats per minute Standard Deviation 12.22	-4.6 beats per minute Standard Deviation 23.40
Change From Baseline in Heart Rate of Participants Change at Day 15	3.7 beats per minute Standard Deviation 8.60	-4.3 beats per minute Standard Deviation 10.56	-1.8 beats per minute Standard Deviation 11.11	-1.9 beats per minute Standard Deviation 16.07
Change From Baseline in Heart Rate of Participants Change at Day 22	-1.7 beats per minute Standard Deviation 11.86	-8.0 beats per minute Standard Deviation 5.85	-0.9 beats per minute Standard Deviation 10.38	-7.4 beats per minute Standard Deviation 20.56
Change From Baseline in Heart Rate of Participants Change at Day 52	-10.0 beats per minute Standard Deviation NA Standard deviation was not estimable due to 1 participant with change in heart rate.	-15.0 beats per minute Standard Deviation NA Standard deviation was not estimable due to 1 participant with change in heart rate.	1.7 beats per minute Standard Deviation 2.52	-0.8 beats per minute Standard Deviation 8.04

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)

Population: Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows.

Respiratory rate was measured in terms of breaths per minute.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Change From Baseline in Respiratory Rate of Participants Baseline	17.6 breaths per minute Standard Deviation 0.88	18.4 breaths per minute Standard Deviation 0.88	18.3 breaths per minute Standard Deviation 1.67	17.8 breaths per minute Standard Deviation 4.71
Change From Baseline in Respiratory Rate of Participants Change at Day 8	0.2 breaths per minute Standard Deviation 0.67	-0.3 breaths per minute Standard Deviation 1.58	0.5 breaths per minute Standard Deviation 2.07	-0.8 breaths per minute Standard Deviation 4.40
Change From Baseline in Respiratory Rate of Participants Change at Day 15	0.9 breaths per minute Standard Deviation 1.05	-0.8 breaths per minute Standard Deviation 1.72	0.0 breaths per minute Standard Deviation 2.14	-1.0 breaths per minute Standard Deviation 4.00
Change From Baseline in Respiratory Rate of Participants Change at Day 22	0.2 breaths per minute Standard Deviation 0.67	-1.1 breaths per minute Standard Deviation 1.36	0.6 breaths per minute Standard Deviation 2.45	-1.0 breaths per minute Standard Deviation 4.00
Change From Baseline in Respiratory Rate of Participants Change at Day 52	0.0 breaths per minute Standard Deviation NA Standard deviation was not estimable due to 1 participant with change in respiratory rate.	1.0 breaths per minute Standard Deviation NA Standard deviation was not estimable due to 1 participant with change in respiratory rate.	1.3 breaths per minute Standard Deviation 2.31	-1.4 breaths per minute Standard Deviation 6.31

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)

Population: Safety analysis included all participants who received any amount of talazoparib. Here, "number analyzed" signifies participants evaluable for specific rows.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Change From Baseline in Body Weight of Participants Change at Day 8	0.16 kilograms Standard Deviation 1.030	-0.62 kilograms Standard Deviation 0.424	-0.26 kilograms Standard Deviation 0.912	-0.26 kilograms Standard Deviation 1.834
Change From Baseline in Body Weight of Participants Baseline	68.60 kilograms Standard Deviation 14.651	69.12 kilograms Standard Deviation 14.914	85.84 kilograms Standard Deviation 20.221	66.79 kilograms Standard Deviation 13.277
Change From Baseline in Body Weight of Participants Change at Day 15	-0.17 kilograms Standard Deviation 1.707	-0.38 kilograms Standard Deviation 1.045	0.05 kilograms Standard Deviation 1.590	-0.23 kilograms Standard Deviation 2.371
Change From Baseline in Body Weight of Participants Change at Day 22	-0.43 kilograms Standard Deviation 2.366	-0.78 kilograms Standard Deviation 1.058	0.04 kilograms Standard Deviation 1.722	-0.75 kilograms Standard Deviation 3.189
Change From Baseline in Body Weight of Participants Change at Day 52	4.90 kilograms Standard Deviation NA Standard deviation was not estimable due to 1 participant with change in weight.	0.70 kilograms Standard Deviation NA Standard deviation was not estimable due to 1 participant with change in weight.	-0.67 kilograms Standard Deviation 2.122	2.88 kilograms Standard Deviation 14.597

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (up to 52 days)

Population: Safety analysis included all participants who received any amount of talazoparib.

ECG parameters included pulse rate (PR) interval, QRS duration, QT interval and corrected QT interval using Fridericia's formula (QTcF). Abnormality criteria: 1) PR interval: greater than equal to (\>=) 25 percent (%) increase when baseline \>= 300 msec; 2) QRS duration: \>=50% increase when baseline \>=140 msec; 3) QT interval: \>= 500 msec: 4) QTCF interval: QTc interval using Fridericia's formula (QTcF interval) \>= 500 msec when baseline \>= 60. IFB stands for increase from baseline.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Number of Participants With Electrocardiogram (ECG) Abnormalities	2 Participants	1 Participants	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (up to 52 days)

Population: Safety analysis included all participants who received any amount of talazoparib.

Laboratory parameters: erythrocytes, hematocrit, hemoglobin, white blood cells, absolute neutrophil count, lymphocytes, platelets ; albumin, alkaline phosphatase, alanine aminotransferase, aspartate transaminase , bilirubin, bicarbonate, blood urea nitrogen , calcium, chloride, creatinine, gamma -glutamyl transferase, glucose, lactate dehydrogenase, sodium, phosphate, potassium, total protein, uric acid, follicle-stimulating hormone; international normalized ratio / prothrombin time \[activated\] partial thromboplastin time; Urinalysis (pH, specific gravity, protein, glucose, ketones, bilirubin, blood, leukocyte esterase); Serum pregnancy test; Serology for Human Immunodeficiency Virus (HIV). Number of participants with laboratory test abnormalities as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) version 4.03 were reported: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=9 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Number of Participants With Laboratory Abnormalities Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities Grade 1	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities Grade 2	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities Grade 4	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Safety follow up (Day 52)

Population: Safety analysis included all participants who received any amount of talazoparib. Here, "Number Analyzed" signifies participants who were evaluable at specific rows.

As per ECOG, participant's performance status was measured on 5 point scale: 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: 5: dead.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 Participants Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 Participants Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 Participants Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Baseline · ECOG: 0	3 Participants	2 Participants	1 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Baseline · ECOG: 1	4 Participants	7 Participants	5 Participants	4 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Baseline · ECOG: 2	2 Participants	0 Participants	2 Participants	3 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Baseline · ECOG: 3	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Baseline · ECOG: 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Day 52 · ECOG: 0	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Day 52 · ECOG: 1	1 Participants	0 Participants	3 Participants	2 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Day 52 · ECOG: 2	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Day 52 · ECOG: 3	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Day 52 · ECOG: 4	0 Participants	0 Participants	0 Participants	1 Participants

Adverse Events

Normal Renal Function

Serious events: 1 serious events

Other events: 7 other events

Deaths: 1 deaths

Mild Renal Impairment

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Moderate Renal Impairment

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Severe Renal Impairment

Serious events: 2 serious events

Other events: 7 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Normal Renal Function n=9 participants at risk Participants with normal renal function (eGFR \>= 90 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Mild Renal Impairment n=9 participants at risk Participants with mild renal function (eGFR \>= 60 and \>=89 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Moderate Renal Impairment n=8 participants at risk Participants with moderate renal function (eGFR \>= 30 and \<=59 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.	Severe Renal Impairment n=8 participants at risk Participants with severe renal function (eGFR \>= 15 and \<= 29 mL/min/1.73m\^2) received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.
General disorders CONDITION AGGRAVATED	11.1% 1/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.
Infections and infestations PNEUMONIA	0.00% 0/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	12.5% 1/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.
Metabolism and nutrition disorders DEHYDRATION	0.00% 0/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	12.5% 1/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.
Metabolism and nutrition disorders METABOLIC ACIDOSIS	0.00% 0/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	12.5% 1/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 0/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/9 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	0.00% 0/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.	12.5% 1/8 • Baseline up to 30 days after last dose of study drug (up to 52 days) 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.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER