Trial Outcomes & Findings for A Study to Assess the Effects of Talazoparib on Cardiac Repolarization in Patients With Advanced Solid Tumors (NCT NCT03042910)
NCT ID: NCT03042910
Last Updated: 2019-12-17
Results Overview
QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole.
COMPLETED
PHASE1
38 participants
Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22
2019-12-17
Participant Flow
Study was conducted in 4 countries from 07-Nov-2016 to 18 Dec 2017.
Participant milestones
| Measure |
Talazoparib 1 mg QD
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Overall Study
STARTED
|
38
|
|
Overall Study
Treated
|
37
|
|
Overall Study
COMPLETED
|
31
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Talazoparib 1 mg QD
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Disease Progression
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Enrolled but not treated
|
1
|
Baseline Characteristics
A Study to Assess the Effects of Talazoparib on Cardiac Repolarization in Patients With Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Age, Continuous
Mean Age
|
64.1 YEARS
STANDARD_DEVIATION 12.82 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
31 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22Population: Electrocardiographic analysis population: all enrolled participants who received at least 1 dose of talazoparib, and had at least 1 available baseline and 1 on-treatment electrocardiogram (ECG) data.
QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 1, 6 hours
|
-0.3 millisecond (msec)
Interval -4.0 to 3.4
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 1, 1 hour
|
3.9 millisecond (msec)
Interval -0.6 to 8.4
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 1, 2 hours
|
3.5 millisecond (msec)
Interval -0.7 to 7.8
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 1, 4 hours
|
1.6 millisecond (msec)
Interval -1.3 to 4.5
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 2, pre-dose
|
-3.5 millisecond (msec)
Interval -8.0 to 1.1
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 22, pre-dose
|
-1.3 millisecond (msec)
Interval -6.1 to 3.6
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 22, 1 hour
|
6.9 millisecond (msec)
Interval 2.2 to 11.5
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 22, 2 hours
|
4.7 millisecond (msec)
Interval -0.2 to 9.5
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 22, 4 hours
|
3.0 millisecond (msec)
Interval -1.4 to 7.3
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Day 22, 6 hours
|
0.5 millisecond (msec)
Interval -4.1 to 5.0
|
PRIMARY outcome
Timeframe: Baseline (Day -1) to Day 22Population: Pharmacokinetic-Pharmacodynamic analysis population: participants who received at least 1 dose of talazoparib, had at least 1 available baseline and 1 on-treatment ECG data, had at least 1 time-matched pair of plasma concentration and ECG measurement obtained at the same nominal time point and met the additional requirements for PK-PD analysis.
A linear mixed effects modeling approach was used to examine the relationship between the change from baseline in QTcF and the plasma concentration of talazoparib. The model included plasma concentration, time (categorical), and treatment with random participant effects on plasma concentration and the intercept. Equation used for modeling was: Y\_lkt= μ\_l+ p\_t+ θ × C\_lkt + W\_k + D\_k × C\_kt + ε\_lkt, where the dependent variable Y\_lkt was for the l (treatment), k (participants) and t (time point). Parameter were: μ\_l was the treatment specific intercept, θ was the slope, C was the concentration, W\_k was the random patient effect on the intercept, D\_k was the random patient effect on the slope, p\_t was the time effect on the intercept and ε\_lkt was the residual error.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Intercept of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22
|
4.6 msec
Interval -3.2 to 12.5
|
PRIMARY outcome
Timeframe: Baseline (Day -1) to Day 22Population: Pharmacokinetic-Pharmacodynamic analysis population: participants who received at least 1 dose of talazoparib, had at least 1 available baseline and 1 on-treatment ECG data, had at least 1 time-matched pair of plasma concentration and ECG measurement obtained at the same nominal time point and met the additional requirements for PK-PD analysis.
A linear mixed effects modeling approach was used to examine the relationship between the change from baseline in QTcF and the plasma concentration of talazoparib. The model included plasma concentration, time (categorical), and treatment with random participant effects on plasma concentration and the intercept. Equation used for modeling was: Y\_lkt= μ\_l+ p\_t+ θ × C\_lkt+ W\_k+ D\_k × C\_kt+ ε\_lkt, where the dependent variable Y\_lkt was for the l (treatment), k (participants) and t (time point). Parameter were: μ\_l was the treatment specific intercept, θ was the slope, C was the concentration, W\_k was the random patient effect on the intercept, D\_k was the random patient effect on the slope, p\_t was the time effect on the intercept and ε\_lkt was the residual error.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Concentration Slope of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22
|
-0.14 msec/nanogram/milliliter (msec/ng/mL)
Interval -0.78 to 0.5
|
SECONDARY outcome
Timeframe: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22Population: Electrocardiographic analysis population: all enrolled participants who received at least 1 dose of talazoparib, and had at least 1 available baseline and 1 on-treatment electrocardiogram (ECG) data.
QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 1, 1 hour
|
0.6 msec
Interval -3.2 to 4.4
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 1, 2 hours
|
4.7 msec
Interval 0.4 to 9.0
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 1, 4 hours
|
2.9 msec
Interval -0.6 to 6.4
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 1, 6 hours
|
-0.4 msec
Interval -4.3 to 3.5
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 2, pre-dose
|
-1.7 msec
Interval -6.2 to 2.8
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 22, pre-dose
|
-2.4 msec
Interval -7.0 to 2.3
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 22, 1 hour
|
1.1 msec
Interval -3.8 to 6.0
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 22, 2 hours
|
2.2 msec
Interval -3.0 to 7.4
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 22, 4 hours
|
1.6 msec
Interval -3.3 to 6.6
|
|
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Day 22, 6 hours
|
0.0 msec
Interval -4.7 to 4.7
|
SECONDARY outcome
Timeframe: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22Population: Electrocardiographic analysis population: all enrolled participants who received at least 1 dose of talazoparib, and had at least 1 available baseline and 1 on-treatment electrocardiogram (ECG) data.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 1, 1 hour
|
-3.0 beats per minute (bpm)
Interval -6.0 to 0.1
|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 1, 2 hours
|
1.4 beats per minute (bpm)
Interval -1.2 to 4.0
|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 1, 4 hours
|
1.4 beats per minute (bpm)
Interval -0.8 to 3.7
|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 1, 6 hours
|
0.1 beats per minute (bpm)
Interval -1.5 to 1.8
|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 2, pre-dose
|
2.3 beats per minute (bpm)
Interval -0.3 to 4.9
|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 22, pre-dose
|
-1.1 beats per minute (bpm)
Interval -5.1 to 2.8
|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 22, 1 hour
|
-6.0 beats per minute (bpm)
Interval -9.3 to -2.6
|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 22, 2 hours
|
-2.8 beats per minute (bpm)
Interval -5.5 to -0.1
|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 22, 4 hours
|
-1.4 beats per minute (bpm)
Interval -4.7 to 1.8
|
|
Time-matched Mean Change From Baseline in Heart Rate
Day 22, 6 hours
|
-0.1 beats per minute (bpm)
Interval -3.3 to 3.0
|
SECONDARY outcome
Timeframe: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22Population: Electrocardiographic analysis population: all enrolled participants who received at least 1 dose of talazoparib, and had at least 1 available baseline and 1 on-treatment electrocardiogram (ECG) data.
PR interval is the time between the beginning of the P wave and the start of the QRS interval, corresponding to the end of atrial depolarization and onset of ventricular depolarization.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Time-matched Mean Change From Baseline in PR Interval
Day 1, 1 hour
|
-2.3 msec
Interval -4.3 to -0.3
|
|
Time-matched Mean Change From Baseline in PR Interval
Day 1, 2 hours
|
-2.2 msec
Interval -4.3 to -0.2
|
|
Time-matched Mean Change From Baseline in PR Interval
Day 1, 4 hours
|
-3.2 msec
Interval -5.7 to -0.7
|
|
Time-matched Mean Change From Baseline in PR Interval
Day 1, 6 hours
|
-1.1 msec
Interval -4.0 to 1.8
|
|
Time-matched Mean Change From Baseline in PR Interval
Day 2, pre-dose
|
-4.5 msec
Interval -7.1 to -1.9
|
|
Time-matched Mean Change From Baseline in PR Interval
Day 22, pre-dose
|
-1.0 msec
Interval -4.6 to 2.5
|
|
Time-matched Mean Change From Baseline in PR Interval
Day 22, 1 hour
|
0.5 msec
Interval -3.3 to 4.3
|
|
Time-matched Mean Change From Baseline in PR Interval
Day 22, 2 hours
|
-0.1 msec
Interval -4.0 to 3.9
|
|
Time-matched Mean Change From Baseline in PR Interval
Day 22, 4 hours
|
-0.1 msec
Interval -3.1 to 3.0
|
|
Time-matched Mean Change From Baseline in PR Interval
Day 22, 6 hours
|
-2.4 msec
Interval -5.4 to 0.6
|
SECONDARY outcome
Timeframe: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22Population: Electrocardiographic analysis population: all enrolled participants who received at least 1 dose of talazoparib, and had at least 1 available baseline and 1 on-treatment electrocardiogram (ECG) data.
QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 1, 1 hour
|
2.9 msec
Interval 0.7 to 5.2
|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 1, 2 hours
|
2.0 msec
Interval -0.6 to 4.6
|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 1, 4 hours
|
1.1 msec
Interval -0.8 to 3.1
|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 1, 6 hours
|
0.9 msec
Interval -1.7 to 3.6
|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 2, pre-dose
|
2.6 msec
Interval 0.3 to 4.8
|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 22, pre-dose
|
0.7 msec
Interval -2.4 to 3.9
|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 22, 1 hour
|
2.6 msec
Interval -0.2 to 5.4
|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 22, 2 hours
|
1.3 msec
Interval -1.8 to 4.4
|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 22, 4 hours
|
1.7 msec
Interval -1.1 to 4.4
|
|
Time-matched Mean Change From Baseline in QRS Interval
Day 22, 6 hours
|
0.7 msec
Interval -2.5 to 3.9
|
SECONDARY outcome
Timeframe: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22Population: Electrocardiographic analysis population: all enrolled participants who received at least 1 dose of talazoparib, and had at least 1 available baseline and 1 on-treatment electrocardiogram (ECG) data.
QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Time-matched Mean Change From Baseline in QT Interval
Day 1, 1 hour
|
10.2 msec
Interval 1.9 to 18.4
|
|
Time-matched Mean Change From Baseline in QT Interval
Day 1, 2 hours
|
1.8 msec
Interval -4.9 to 8.4
|
|
Time-matched Mean Change From Baseline in QT Interval
Day 1, 4 hours
|
-0.9 msec
Interval -5.4 to 3.6
|
|
Time-matched Mean Change From Baseline in QT Interval
Day 1, 6 hours
|
0.0 msec
Interval -4.8 to 4.8
|
|
Time-matched Mean Change From Baseline in QT Interval
Day 2, pre-dose
|
-6.5 msec
Interval -13.7 to 0.8
|
|
Time-matched Mean Change From Baseline in QT Interval
Day 22, pre-dose
|
0.8 msec
Interval -8.6 to 10.1
|
|
Time-matched Mean Change From Baseline in QT Interval
Day 22, 1 hour
|
17.6 msec
Interval 9.1 to 26.0
|
|
Time-matched Mean Change From Baseline in QT Interval
Day 22, 2 hours
|
9.1 msec
Interval 1.4 to 16.7
|
|
Time-matched Mean Change From Baseline in QT Interval
Day 22, 4 hours
|
5.2 msec
Interval -1.6 to 12.0
|
|
Time-matched Mean Change From Baseline in QT Interval
Day 22, 6 hours
|
1.2 msec
Interval -6.6 to 9.0
|
SECONDARY outcome
Timeframe: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22Population: Electrocardiographic analysis population: all enrolled participants who received at least 1 dose of talazoparib, and had at least 1 available baseline and 1 on-treatment electrocardiogram (ECG) data.
RR interval is the time elapsing between two consecutive R waves in the electrocardiogram.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Time-matched Mean Change From Baseline in RR Interval
Day 22, 1 hour
|
69.8 msec
Interval 29.3 to 110.3
|
|
Time-matched Mean Change From Baseline in RR Interval
Day 1, 1 hour
|
42.9 msec
Interval 10.7 to 75.0
|
|
Time-matched Mean Change From Baseline in RR Interval
Day 1, 2 hours
|
-7.8 msec
Interval -34.9 to 19.3
|
|
Time-matched Mean Change From Baseline in RR Interval
Day 1, 4 hours
|
-15.1 msec
Interval -37.7 to 7.6
|
|
Time-matched Mean Change From Baseline in RR Interval
Day 1, 6 hours
|
2.1 msec
Interval -16.4 to 20.6
|
|
Time-matched Mean Change From Baseline in RR Interval
Day 2, pre-dose
|
-17.9 msec
Interval -47.4 to 11.7
|
|
Time-matched Mean Change From Baseline in RR Interval
Day 22, pre-dose
|
16.0 msec
Interval -25.7 to 57.8
|
|
Time-matched Mean Change From Baseline in RR Interval
Day 22, 2 hours
|
30.5 msec
Interval -4.3 to 65.3
|
|
Time-matched Mean Change From Baseline in RR Interval
Day 22, 4 hours
|
15.6 msec
Interval -16.2 to 47.4
|
|
Time-matched Mean Change From Baseline in RR Interval
Day 22, 6 hours
|
4.1 msec
Interval -30.9 to 39.1
|
SECONDARY outcome
Timeframe: Baseline to Day 22Population: Electrocardiographic analysis population: all enrolled participants who received at least 1 dose of talazoparib, and had at least 1 available baseline and 1 on-treatment electrocardiogram (ECG) data.
Morphological analyses were performed with regard to the ECG waveform interpretation as defined by the central ECG laboratory's cardiologist. Numbers of participants with new onsets for the following variables were counted: atrial fibrillation or flutter, second-degree heart block, third degree heart block, complete right bundle branch block, complete left bundle branch block, ST segment depression, ST segment elevation, T-wave abnormalities (negative T waves only), myocardial infarction pattern, and any new abnormal U waves. "New" was defined as "not present on any baseline ECG but present on any on-treatment ECG". Number of participants with abnormality in any of the variables were reported.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Number of Participants With Treatment-emergent Abnormalities in 12-lead Electrocardiogram (ECG) Morphpology
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (mean of all ECGs on Day -1 and pre-dose on Day 1) to Day 22Population: Electrocardiographic analysis population: all enrolled participants who received at least 1 dose of talazoparib, and had at least 1 available baseline and 1 on-treatment electrocardiogram (ECG) data.
Criteria for clinically significant: Maximum QTcF \>450 msec, Maximum QTcF \>480 msec, Maximum QTcF \>500 msec, Maximum QTcB \>450 msec, Maximum QTcB \>480 msec, Maximum QTcB \>500 msec, Maximum QT Interval \>500 msec, Maximum QTcF Increase \<=30 msec, Maximum QTcF Increase 30 to \<=60 msec, Maximum QTcF Increase \<=60 msec, Maximum PR interval increase \>200 msec and \>=25%, Maximum QRS interval increase \>100 msec and \>=25%, Maximum heart rate increase \>100 bpm and \>25% and Maximum heart rate decrease \<50 bpm and \>25%.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum heart rate increase >100 bpm and >25%
|
1 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcF >450 msec
|
5 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcF >480 msec
|
1 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcF >500 msec
|
0 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcB >450 msec
|
13 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcB >480 msec
|
2 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcB >500 msec
|
0 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QT Interval >500 msec
|
0 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcF increase <=30 msec
|
33 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcF increase: 30 to <=60 msec
|
4 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcF increase >60 msec
|
0 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcB increase <=30 msec
|
34 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcB increase: 30 to <=60 msec
|
3 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QTcB increase >60 msec
|
0 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum PR interval increase >200 msec and >=25%
|
0 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum QRS interval increase >100 msec and >=25%
|
1 Participants
|
|
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Maximum heart rate decrease <50 bpm and >25%
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)Population: Safety population: all participants who received any amount of talazoparib.
An adverse event(AE)was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not related to the study drug. A serious adverse event(SAE)was an AE that resulted in: death; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect; was life-threatening (immediate risk of death); hospitalization or prolongation of existing hospitalization; or considered to be an important medical event. Treatment-emergent AEs (TEAEs) are AEs occurred on or after the administration of study drug. AEs related to study drug was any AE with at least a possible relationship to the study drug as assessed by the investigator. AEs of special interest were diagnosis of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and abnormal liver test results that met predefined criteria.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
AEs
|
28 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
AEs related to study drug
|
17 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
SAEs
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
SAEs related to study drug
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
Discontinuations due to AEs
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
Deaths
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
AEs of special interest
|
0 Participants
|
SECONDARY outcome
Timeframe: Screening (Day -29 to Day -2) to follow-up (30 days post last dose on Day 22)Population: Safety population: all participants who received any amount of talazoparib.
Clinically notable changes included: High systolic blood pressure (SBP):\>=155 millimeters of mercury (mmHg) with increase \>=30 mmHg, low SBP \<=90 mmHg with decrease \>=20 mmHg, Both high and low SBP (i.e high SBP \>=155 mmHg with increase \>=30 mmHg and low SBP \<=90 mmHg with decrease \>=20 mmHg), High diastolic blood pressure (DBP):\>=100 mmHg with increase \>=15 mmHg), Low DBP (\<=50 mmHg with decrease \>=15 mmHg), Both high and low DBP, Heart rate \>=100 bpm with increase \>=30 bpm, Heart rate \<=50 bpm with decrease \>=15 bpm, Respiratory rate \>=25 bpm, Respiratory rate \<10 bpm, Oral body temperature \>39 degree and Oral body temperature \<=35 degree.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Respiratory rate <10 bpm
|
0 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
High SBP (>=155 mmHg with increase >=30 mmHg)
|
0 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Low SBP (<=90 mmHg with decrease >=20 mmHg)
|
2 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Both high and low SBP
|
0 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
High DBP (>=100 mmHg with increase >=15 mmHg)
|
1 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Low DBP (<=50 mmHg with decrease >=15 mmHg)
|
1 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Both high and low DBP
|
0 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Heart rate >=100 bpm with increase >=30 bpm
|
0 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Heart rate <=50 bpm with decrease >=15 bpm
|
0 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Respiratory rate >=25 bpm
|
0 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Oral body temperature >39 degree
|
0 Participants
|
|
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Oral body temperature <=35 degree
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to follow-up (30 days post last dose on Day 22, i.e. up to Day 52)Population: Safety population: all participants who received any amount of talazoparib.
Laboratory test included: hematology (hematocrit, hemoglobin, mean corpuscular volum, red blood cell count, platelet count, white blood cell count with differential \[total neutrophils, eosinophils, monocytes, basophils, and lymphocytes\]),chemistry (albumin, total protein, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, blood urea nitrogen, creatinine, non-fasting glucose, carbon dioxide, calcium, chloride, magnesium, phosphate, potassium, sodium and lactate dehydrogenase), and additional tests (urine or serum pregnancy tests for women of childbearing potential). Clinically significant laboratory abnormality was determined by the investigator.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Number of Participants With Clinically Significant Laboratory Test Abnormalities
|
3 Participants
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22Population: Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter. Here, number analyzed signifies participants with available date for the specified time point.
Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours After Dosing (AUC24) of Plasma Talazoparib on Day 1 and Day 22
Day 1
|
54200 picogram*hour/milliliter (pg*hr/mL)
Geometric Coefficient of Variation 42
|
|
Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours After Dosing (AUC24) of Plasma Talazoparib on Day 1 and Day 22
Day 22
|
209000 picogram*hour/milliliter (pg*hr/mL)
Geometric Coefficient of Variation 36
|
|
Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours After Dosing (AUC24) of Plasma Talazoparib on Day 1 and Day 22
Day 22 Subpopulation
|
208000 picogram*hour/milliliter (pg*hr/mL)
Geometric Coefficient of Variation 37
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22Population: Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter. Here, number analyzed signifies participants with available date for the specified time point.
Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Maximum Plasma Concentration (Cmax) of Plasma Talazoparib on Day 1 and Day 22
Day 22 Subpopulation
|
16400 picogram/milliliter (pg/mL)
Geometric Coefficient of Variation 32
|
|
Maximum Plasma Concentration (Cmax) of Plasma Talazoparib on Day 1 and Day 22
Day 1
|
4350 picogram/milliliter (pg/mL)
Geometric Coefficient of Variation 47
|
|
Maximum Plasma Concentration (Cmax) of Plasma Talazoparib on Day 1 and Day 22
Day 22
|
16300 picogram/milliliter (pg/mL)
Geometric Coefficient of Variation 32
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22Population: Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter.
Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22
Day 1
|
2.00 hour (hr)
Interval 0.92 to 6.0
|
|
Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22
Day 22
|
2.00 hour (hr)
Interval 0.97 to 6.0
|
|
Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22
Day 22 Subpopulation
|
2.00 hour (hr)
Interval 0.97 to 6.0
|
SECONDARY outcome
Timeframe: Pre-dose, Day 22Population: Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter.
Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Predose Concentration (Ctrough) of Plasma Talazoparib on Day 22
Day 22
|
4990 pg/mL
Geometric Coefficient of Variation 53
|
|
Predose Concentration (Ctrough) of Plasma Talazoparib on Day 22
Day 22 Subpopulation
|
4950 pg/mL
Geometric Coefficient of Variation 56
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22Population: Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter. Here, number analyzed signifies participants with available date for the specified time point.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed. Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Apparent Clearance After Oral Dose (CL/F) of Plasma Talazoparib on Day 22
Day 22
|
4.8 liter/hour (L/hr)
Geometric Coefficient of Variation 36
|
|
Apparent Clearance After Oral Dose (CL/F) of Plasma Talazoparib on Day 22
Day 22 Subpopulation
|
4.8 liter/hour (L/hr)
Geometric Coefficient of Variation 37
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22Population: Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter. Here, number analyzed signifies participants with available date for the specified time point.
Rac was calculated as, area under the curve from time zero to end of dosing interval on Day 22 (AUCtau) divided by area under the curve from time zero to end of dosing interval on Day 1 (AUCtau). Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 6 hours. Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.
Outcome measures
| Measure |
Talazoparib 1 mg QD
n=37 Participants
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Accumulation Ratio (Rac) of Plasma Talazoparib on Day 22
Day 22
|
3.96 ratio
Interval 1.89 to 14.4
|
|
Accumulation Ratio (Rac) of Plasma Talazoparib on Day 22
Day 22 Subpopulation
|
3.98 ratio
Interval 1.89 to 14.4
|
Adverse Events
Talazoparib 1 mg QD
Serious adverse events
| Measure |
Talazoparib 1 mg QD
n=37 participants at risk
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.7%
1/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Blood and lymphatic system disorders
Spontaneous Haemorrhage
|
2.7%
1/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
2.7%
1/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
2.7%
1/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Nervous system disorders
Syncope
|
2.7%
1/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
Other adverse events
| Measure |
Talazoparib 1 mg QD
n=37 participants at risk
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.8%
4/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
8.1%
3/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.1%
3/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Gastrointestinal disorders
Constipation
|
8.1%
3/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Gastrointestinal disorders
Diarrhoea
|
13.5%
5/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Gastrointestinal disorders
Nausea
|
21.6%
8/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Gastrointestinal disorders
Vomiting
|
10.8%
4/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
General disorders
Fatigue
|
24.3%
9/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Investigations
Platelet count decreased
|
8.1%
3/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.4%
2/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Nervous system disorders
Headache
|
8.1%
3/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.1%
3/37 • Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
|
Additional Information
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