Solid Tumor
Conditions
Brief summary
This study is designed to evaluate the effects of talazoparib on cardiac repolarization in patients with advanced solid tumors with no available standard treatment options.
Detailed description
For further talazoparib treatment, patients must enroll and initiate continued talazoparib treatment in a separate open label extension study within 30 days after the last dose of study drug.
Interventions
DRUGTalazoparib
Talazoparib 1 mg orally once daily.
Sponsors
Medivation, Inc.
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years of age and willing and able to provide informed consent. 2. Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the investigator. 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 4. Estimated life expectancy of ≥ 3 months. 5. Able to swallow the study drug, have no known intolerance to the study drug or excipients, and comply with study requirements. 6. Female patients of childbearing potential must have a negative pregnancy test at screening and must agree to use a highly effective birth control method from the time of the first dose of study drug through 45 days after last dose of study drug. 7. Male patients must use a condom when having sex with a pregnant woman or with a woman of childbearing potential from the time of the first dose of study drug through 105 days after last dose of study drug. Contraception should be considered for a nonpregnant female partner of childbearing potential. 8. Male and female patients must agree not to donate sperm or eggs, respectively, from the first dose of study drug through 105 days and 45 days after the last dose of study drug, respectively. 9. Female patients may not be breastfeeding at screening and must not breastfeed during study participation through 45 days after the last dose of study drug.
Exclusion criteria
1. Use of antineoplastic therapies within 21 days before day 1. 2. Use of any other investigational agent within 21 days before day 1. 3. Have not recovered (recovery is defined as National Cancer Institute Common Terminology Criteria for Adverse Events \[CTCAE\] grade ≤ 1) from the acute toxicities of previous therapy, except treatment related alopecia or laboratory abnormalities otherwise meeting eligibility requirements. 4. Electrolyte abnormality that has not responded to correction, including hypokalemia or hypocalcemia less than the lower limit of normal, or hyperkalemia or hypercalcemia greater than the upper limit of normal (ULN). 5. Major surgery within 14 days before day 1. 6. Diagnosis of myelodysplastic syndrome (MDS) or a hematologic malignancy. 7. Clinically significant cardiovascular disease. 8. Significant organ dysfunction. 9. Gastrointestinal disorder affecting absorption. 10. Current or anticipated use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP. 11. Any condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data, in the opinion of the investigator or medical monitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF) | 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 | QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. |
| Intercept of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22 | Baseline (Day -1) to Day 22 | 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. |
| Concentration Slope of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22 | Baseline (Day -1) to Day 22 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-matched Mean Change From Baseline in QRS Interval | 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 | QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization. |
| Time-matched Mean Change From Baseline in QT Interval | 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 | QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. |
| Time-matched Mean Change From Baseline in RR Interval | 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 | RR interval is the time elapsing between two consecutive R waves in the electrocardiogram. |
| Number of Participants With Treatment-emergent Abnormalities in 12-lead Electrocardiogram (ECG) Morphpology | Baseline to Day 22 | 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. |
| Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Baseline (mean of all ECGs on Day -1 and pre-dose on Day 1) to Day 22 | 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%. |
| Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths | Day 1 to follow-up (30 days post last dose, i.e. up to 52 days) | 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. |
| Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Screening (Day -29 to Day -2) to follow-up (30 days post last dose on Day 22) | 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. |
| Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB) | 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 | QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. |
| 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 | 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 22 | 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. |
| Maximum Plasma Concentration (Cmax) of Plasma Talazoparib on Day 1 and Day 22 | 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 22 | 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. |
| Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22 | 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 22 | 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. |
| Predose Concentration (Ctrough) of Plasma Talazoparib on Day 22 | Pre-dose, Day 22 | 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. |
| Apparent Clearance After Oral Dose (CL/F) of Plasma Talazoparib on Day 22 | Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22 | 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. |
| Accumulation Ratio (Rac) of Plasma Talazoparib on Day 22 | Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22 | 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. |
| Number of Participants With Clinically Significant Laboratory Test Abnormalities | Baseline to follow-up (30 days post last dose on Day 22, i.e. up to Day 52) | 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. |
| Time-matched Mean Change From Baseline in Heart Rate | 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 | — |
| Time-matched Mean Change From Baseline in PR Interval | 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 | 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. |
Countries
United States
Participant flow
Pre-assignment details
Study was conducted in 4 countries from 07-Nov-2016 to 18 Dec 2017.
Participants by arm
| Arm | Count |
|---|---|
| Talazoparib 1 mg QD Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Disease Progression | 2 |
| Overall Study | Enrolled but not treated | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Talazoparib 1 mg QD |
|---|---|
| Age, Continuous Mean Age | 64.1 YEARS STANDARD_DEVIATION 12.82 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 31 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 37 |
| other Total, other adverse events | 23 / 37 |
| serious Total, serious adverse events | 3 / 37 |
Outcome results
Primary
Concentration Slope of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22
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.
Time frame: Baseline (Day -1) to Day 22
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talazoparib 1 mg QD | 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) |
Primary
Intercept of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22
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.
Time frame: Baseline (Day -1) to Day 22
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talazoparib 1 mg QD | Intercept of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22 | 4.6 msec |
Primary
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Talazoparib 1 mg QD | 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) |
| Talazoparib 1 mg QD | 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) |
| Talazoparib 1 mg QD | 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) |
| Talazoparib 1 mg QD | 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) |
| Talazoparib 1 mg QD | 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) |
| Talazoparib 1 mg QD | 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) |
| Talazoparib 1 mg QD | 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) |
| Talazoparib 1 mg QD | 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) |
| Talazoparib 1 mg QD | 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) |
| Talazoparib 1 mg QD | 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) |
Secondary
Accumulation Ratio (Rac) of Plasma Talazoparib on Day 22
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.
Time frame: Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Talazoparib 1 mg QD | Accumulation Ratio (Rac) of Plasma Talazoparib on Day 22 | Day 22 | 3.96 ratio |
| Talazoparib 1 mg QD | Accumulation Ratio (Rac) of Plasma Talazoparib on Day 22 | Day 22 Subpopulation | 3.98 ratio |
Secondary
Apparent Clearance After Oral Dose (CL/F) of Plasma Talazoparib on Day 22
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.
Time frame: Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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
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: 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.
Time frame: 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 22
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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
Maximum Plasma Concentration (Cmax) of Plasma Talazoparib on Day 1 and Day 22
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.
Time frame: 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 22
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
Secondary
Number of Participants With Clinically Notable Changes in Vital Signs Measurements
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | High SBP (>=155 mmHg with increase >=30 mmHg) | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Low SBP (<=90 mmHg with decrease >=20 mmHg) | 2 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Both high and low SBP | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | High DBP (>=100 mmHg with increase >=15 mmHg) | 1 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Low DBP (<=50 mmHg with decrease >=15 mmHg) | 1 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Both high and low DBP | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Heart rate >=100 bpm with increase >=30 bpm | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Heart rate <=50 bpm with decrease >=15 bpm | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Respiratory rate >=25 bpm | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Respiratory rate <10 bpm | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Oral body temperature >39 degree | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Notable Changes in Vital Signs Measurements | Oral body temperature <=35 degree | 0 Participants |
Secondary
Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
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%.
Time frame: Baseline (mean of all ECGs on Day -1 and pre-dose on Day 1) to Day 22
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcF >450 msec | 5 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcF >480 msec | 1 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcF >500 msec | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcB >450 msec | 13 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcB >480 msec | 2 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcB >500 msec | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QT Interval >500 msec | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcF increase <=30 msec | 33 Participants |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcF increase >60 msec | 0 Participants |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcB increase <=30 msec | 34 Participants |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria | Maximum QTcB increase >60 msec | 0 Participants |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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
Number of Participants With Clinically Significant Laboratory Test Abnormalities
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib 1 mg QD | Number of Participants With Clinically Significant Laboratory Test Abnormalities | 3 Participants |
Secondary
Number of Participants With Treatment-emergent Abnormalities in 12-lead Electrocardiogram (ECG) Morphpology
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.
Time frame: Baseline to Day 22
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib 1 mg QD | Number of Participants With Treatment-emergent Abnormalities in 12-lead Electrocardiogram (ECG) Morphpology | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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
Predose Concentration (Ctrough) of Plasma Talazoparib on Day 22
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.
Time frame: Pre-dose, Day 22
Population: Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Talazoparib 1 mg QD | Predose Concentration (Ctrough) of Plasma Talazoparib on Day 22 | Day 22 | 4990 pg/mL | Geometric Coefficient of Variation 53 |
| Talazoparib 1 mg QD | Predose Concentration (Ctrough) of Plasma Talazoparib on Day 22 | Day 22 Subpopulation | 4950 pg/mL | Geometric Coefficient of Variation 56 |
Secondary
Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22
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.
Time frame: 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 22
Population: Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Talazoparib 1 mg QD | Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22 | Day 1 | 2.00 hour (hr) |
| Talazoparib 1 mg QD | Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22 | Day 22 | 2.00 hour (hr) |
| Talazoparib 1 mg QD | Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22 | Day 22 Subpopulation | 2.00 hour (hr) |
Secondary
Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
| Talazoparib 1 mg QD | 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 |
Secondary
Time-matched Mean Change From Baseline in Heart Rate
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 1, 2 hours | 1.4 beats per minute (bpm) |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 1, 4 hours | 1.4 beats per minute (bpm) |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 1, 6 hours | 0.1 beats per minute (bpm) |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 2, pre-dose | 2.3 beats per minute (bpm) |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 22, pre-dose | -1.1 beats per minute (bpm) |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 22, 1 hour | -6.0 beats per minute (bpm) |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 22, 2 hours | -2.8 beats per minute (bpm) |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 22, 4 hours | -1.4 beats per minute (bpm) |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 22, 6 hours | -0.1 beats per minute (bpm) |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in Heart Rate | Day 1, 1 hour | -3.0 beats per minute (bpm) |
Secondary
Time-matched Mean Change From Baseline in PR Interval
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 1, 1 hour | -2.3 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 1, 2 hours | -2.2 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 1, 4 hours | -3.2 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 1, 6 hours | -1.1 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 2, pre-dose | -4.5 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 22, pre-dose | -1.0 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 22, 1 hour | 0.5 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 22, 2 hours | -0.1 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 22, 4 hours | -0.1 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in PR Interval | Day 22, 6 hours | -2.4 msec |
Secondary
Time-matched Mean Change From Baseline in QRS Interval
QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 1, 1 hour | 2.9 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 1, 2 hours | 2.0 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 1, 4 hours | 1.1 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 1, 6 hours | 0.9 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 2, pre-dose | 2.6 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 22, pre-dose | 0.7 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 22, 1 hour | 2.6 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 22, 2 hours | 1.3 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 22, 4 hours | 1.7 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QRS Interval | Day 22, 6 hours | 0.7 msec |
Secondary
Time-matched Mean Change From Baseline in QT Interval
QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 1, 1 hour | 10.2 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 1, 2 hours | 1.8 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 1, 4 hours | -0.9 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 1, 6 hours | 0.0 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 2, pre-dose | -6.5 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 22, pre-dose | 0.8 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 22, 1 hour | 17.6 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 22, 2 hours | 9.1 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 22, 4 hours | 5.2 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in QT Interval | Day 22, 6 hours | 1.2 msec |
Secondary
Time-matched Mean Change From Baseline in RR Interval
RR interval is the time elapsing between two consecutive R waves in the electrocardiogram.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 1, 1 hour | 42.9 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 1, 2 hours | -7.8 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 1, 4 hours | -15.1 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 1, 6 hours | 2.1 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 2, pre-dose | -17.9 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 22, pre-dose | 16.0 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 22, 1 hour | 69.8 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 22, 2 hours | 30.5 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 22, 4 hours | 15.6 msec |
| Talazoparib 1 mg QD | Time-matched Mean Change From Baseline in RR Interval | Day 22, 6 hours | 4.1 msec |