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A Study to Assess the Effects of Talazoparib on Cardiac Repolarization in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03042910
Recruitment Status : Completed
First Posted : February 3, 2017
Results First Posted : December 17, 2019
Last Update Posted : December 17, 2019
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Tumor
Intervention Drug: Talazoparib
Enrollment 38
Recruitment Details  
Pre-assignment Details Study was conducted in 4 countries from 07-Nov-2016 to 18 Dec 2017.
Arm/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Period Title: Overall Study
Started 38
Treated 37
Completed 31
Not Completed 7
Reason Not Completed
Adverse Event             1
Disease Progression             2
Withdrawal by Subject             3
Enrolled but not treated             1
Arm/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Baseline Participants 37
Hide Baseline Analysis Population Description
Safety population: all participants who received any amount of talazoparib.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  YEARS
Mean Age Number Analyzed 37 participants
64.1  (12.82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
23
  62.2%
Male
14
  37.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 37 participants
American Indian or Alaska Native 1
Black or African American 2
Native Hawaiian or other Pacific Islander 1
Other 2
White 31
1.Primary Outcome
Title Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Mean (90% Confidence Interval)
Unit of Measure: millisecond (msec)
Day 1, 1 hour Number Analyzed 36 participants
3.9
(-0.6 to 8.4)
Day 1, 2 hours Number Analyzed 33 participants
3.5
(-0.7 to 7.8)
Day 1, 4 hours Number Analyzed 35 participants
1.6
(-1.3 to 4.5)
Day 1, 6 hours Number Analyzed 29 participants
-0.3
(-4.0 to 3.4)
Day 2, pre-dose Number Analyzed 32 participants
-3.5
(-8.0 to 1.1)
Day 22, pre-dose Number Analyzed 27 participants
-1.3
(-6.1 to 3.6)
Day 22, 1 hour Number Analyzed 30 participants
6.9
(2.2 to 11.5)
Day 22, 2 hours Number Analyzed 28 participants
4.7
(-0.2 to 9.5)
Day 22, 4 hours Number Analyzed 30 participants
3.0
(-1.4 to 7.3)
Day 22, 6 hours Number Analyzed 25 participants
0.5
(-4.1 to 5.0)
2.Primary Outcome
Title Intercept of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: msec
4.6
(-3.2 to 12.5)
3.Primary Outcome
Title Concentration Slope of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: msec/nanogram/milliliter (msec/ng/mL)
-0.14
(-0.78 to 0.50)
4.Secondary Outcome
Title Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Mean (90% Confidence Interval)
Unit of Measure: msec
Day 1, 1 hour Number Analyzed 36 participants
0.6
(-3.2 to 4.4)
Day 1, 2 hours Number Analyzed 33 participants
4.7
(0.4 to 9.0)
Day 1, 4 hours Number Analyzed 35 participants
2.9
(-0.6 to 6.4)
Day 1, 6 hours Number Analyzed 29 participants
-0.4
(-4.3 to 3.5)
Day 2, pre-dose Number Analyzed 32 participants
-1.7
(-6.2 to 2.8)
Day 22, pre-dose Number Analyzed 27 participants
-2.4
(-7.0 to 2.3)
Day 22, 1 hour Number Analyzed 30 participants
1.1
(-3.8 to 6.0)
Day 22, 2 hours Number Analyzed 28 participants
2.2
(-3.0 to 7.4)
Day 22, 4 hours Number Analyzed 30 participants
1.6
(-3.3 to 6.6)
Day 22, 6 hours Number Analyzed 25 participants
0.0
(-4.7 to 4.7)
5.Secondary Outcome
Title Time-matched Mean Change From Baseline in Heart Rate
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Mean (90% Confidence Interval)
Unit of Measure: beats per minute (bpm)
Day 1, 1 hour Number Analyzed 36 participants
-3.0
(-6.0 to 0.1)
Day 1, 2 hours Number Analyzed 33 participants
1.4
(-1.2 to 4.0)
Day 1, 4 hours Number Analyzed 35 participants
1.4
(-0.8 to 3.7)
Day 1, 6 hours Number Analyzed 29 participants
0.1
(-1.5 to 1.8)
Day 2, pre-dose Number Analyzed 32 participants
2.3
(-0.3 to 4.9)
Day 22, pre-dose Number Analyzed 27 participants
-1.1
(-5.1 to 2.8)
Day 22, 1 hour Number Analyzed 30 participants
-6.0
(-9.3 to -2.6)
Day 22, 2 hours Number Analyzed 28 participants
-2.8
(-5.5 to -0.1)
Day 22, 4 hours Number Analyzed 30 participants
-1.4
(-4.7 to 1.8)
Day 22, 6 hours Number Analyzed 25 participants
-0.1
(-3.3 to 3.0)
6.Secondary Outcome
Title Time-matched Mean Change From Baseline in PR Interval
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Mean (90% Confidence Interval)
Unit of Measure: msec
Day 1, 1 hour Number Analyzed 36 participants
-2.3
(-4.3 to -0.3)
Day 1, 2 hours Number Analyzed 33 participants
-2.2
(-4.3 to -0.2)
Day 1, 4 hours Number Analyzed 35 participants
-3.2
(-5.7 to -0.7)
Day 1, 6 hours Number Analyzed 29 participants
-1.1
(-4.0 to 1.8)
Day 2, pre-dose Number Analyzed 32 participants
-4.5
(-7.1 to -1.9)
Day 22, pre-dose Number Analyzed 27 participants
-1.0
(-4.6 to 2.5)
Day 22, 1 hour Number Analyzed 30 participants
0.5
(-3.3 to 4.3)
Day 22, 2 hours Number Analyzed 28 participants
-0.1
(-4.0 to 3.9)
Day 22, 4 hours Number Analyzed 30 participants
-0.1
(-3.1 to 3.0)
Day 22, 6 hours Number Analyzed 25 participants
-2.4
(-5.4 to 0.6)
7.Secondary Outcome
Title Time-matched Mean Change From Baseline in QRS Interval
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Mean (90% Confidence Interval)
Unit of Measure: msec
Day 1, 1 hour Number Analyzed 36 participants
2.9
(0.7 to 5.2)
Day 1, 2 hours Number Analyzed 33 participants
2.0
(-0.6 to 4.6)
Day 1, 4 hours Number Analyzed 35 participants
1.1
(-0.8 to 3.1)
Day 1, 6 hours Number Analyzed 29 participants
0.9
(-1.7 to 3.6)
Day 2, pre-dose Number Analyzed 32 participants
2.6
(0.3 to 4.8)
Day 22, pre-dose Number Analyzed 27 participants
0.7
(-2.4 to 3.9)
Day 22, 1 hour Number Analyzed 30 participants
2.6
(-0.2 to 5.4)
Day 22, 2 hours Number Analyzed 28 participants
1.3
(-1.8 to 4.4)
Day 22, 4 hours Number Analyzed 30 participants
1.7
(-1.1 to 4.4)
Day 22, 6 hours Number Analyzed 25 participants
0.7
(-2.5 to 3.9)
8.Secondary Outcome
Title Time-matched Mean Change From Baseline in QT Interval
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Mean (90% Confidence Interval)
Unit of Measure: msec
Day 1, 1 hour Number Analyzed 36 participants
10.2
(1.9 to 18.4)
Day 1, 2 hours Number Analyzed 33 participants
1.8
(-4.9 to 8.4)
Day 1, 4 hours Number Analyzed 35 participants
-0.9
(-5.4 to 3.6)
Day 1, 6 hours Number Analyzed 29 participants
0.0
(-4.8 to 4.8)
Day 2, pre-dose Number Analyzed 32 participants
-6.5
(-13.7 to 0.8)
Day 22, pre-dose Number Analyzed 27 participants
0.8
(-8.6 to 10.1)
Day 22, 1 hour Number Analyzed 30 participants
17.6
(9.1 to 26.0)
Day 22, 2 hours Number Analyzed 28 participants
9.1
(1.4 to 16.7)
Day 22, 4 hours Number Analyzed 30 participants
5.2
(-1.6 to 12.0)
Day 22, 6 hours Number Analyzed 25 participants
1.2
(-6.6 to 9.0)
9.Secondary Outcome
Title Time-matched Mean Change From Baseline in RR Interval
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Mean (90% Confidence Interval)
Unit of Measure: msec
Day 1, 1 hour Number Analyzed 36 participants
42.9
(10.7 to 75.0)
Day 1, 2 hours Number Analyzed 33 participants
-7.8
(-34.9 to 19.3)
Day 1, 4 hours Number Analyzed 35 participants
-15.1
(-37.7 to 7.6)
Day 1, 6 hours Number Analyzed 29 participants
2.1
(-16.4 to 20.6)
Day 2, pre-dose Number Analyzed 32 participants
-17.9
(-47.4 to 11.7)
Day 22, pre-dose Number Analyzed 27 participants
16.0
(-25.7 to 57.8)
Day 22, 1 hour Number Analyzed 30 participants
69.8
(29.3 to 110.3)
Day 22, 2 hours Number Analyzed 28 participants
30.5
(-4.3 to 65.3)
Day 22, 4 hours Number Analyzed 30 participants
15.6
(-16.2 to 47.4)
Day 22, 6 hours Number Analyzed 25 participants
4.1
(-30.9 to 39.1)
10.Secondary Outcome
Title Number of Participants With Treatment-emergent Abnormalities in 12-lead Electrocardiogram (ECG) Morphpology
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
11.Secondary Outcome
Title Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
Maximum QTcF >450 msec
5
  13.5%
Maximum QTcF >480 msec
1
   2.7%
Maximum QTcF >500 msec
0
   0.0%
Maximum QTcB >450 msec
13
  35.1%
Maximum QTcB >480 msec
2
   5.4%
Maximum QTcB >500 msec
0
   0.0%
Maximum QT Interval >500 msec
0
   0.0%
Maximum QTcF increase <=30 msec
33
  89.2%
Maximum QTcF increase: 30 to <=60 msec
4
  10.8%
Maximum QTcF increase >60 msec
0
   0.0%
Maximum QTcB increase <=30 msec
34
  91.9%
Maximum QTcB increase: 30 to <=60 msec
3
   8.1%
Maximum QTcB increase >60 msec
0
   0.0%
Maximum PR interval increase >200 msec and >=25%
0
   0.0%
Maximum QRS interval increase >100 msec and >=25%
1
   2.7%
Maximum heart rate increase >100 bpm and >25%
1
   2.7%
Maximum heart rate decrease <50 bpm and >25%
0
   0.0%
12.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all participants who received any amount of talazoparib.
Arm/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
28
  75.7%
AEs related to study drug
17
  45.9%
SAEs
3
   8.1%
SAEs related to study drug
1
   2.7%
Discontinuations due to AEs
0
   0.0%
Deaths
0
   0.0%
AEs of special interest
0
   0.0%
13.Secondary Outcome
Title Number of Participants With Clinically Notable Changes in Vital Signs Measurements
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all participants who received any amount of talazoparib.
Arm/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
High SBP (>=155 mmHg with increase >=30 mmHg)
0
   0.0%
Low SBP (<=90 mmHg with decrease >=20 mmHg)
2
   5.4%
Both high and low SBP
0
   0.0%
High DBP (>=100 mmHg with increase >=15 mmHg)
1
   2.7%
Low DBP (<=50 mmHg with decrease >=15 mmHg)
1
   2.7%
Both high and low DBP
0
   0.0%
Heart rate >=100 bpm with increase >=30 bpm
0
   0.0%
Heart rate <=50 bpm with decrease >=15 bpm
0
   0.0%
Respiratory rate >=25 bpm
0
   0.0%
Respiratory rate <10 bpm
0
   0.0%
Oral body temperature >39 degree
0
   0.0%
Oral body temperature <=35 degree
0
   0.0%
14.Secondary Outcome
Title Number of Participants With Clinically Significant Laboratory Test Abnormalities
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all participants who received any amount of talazoparib.
Arm/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
3
   8.1%
15.Secondary Outcome
Title 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
Hide Description 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
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Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: picogram*hour/milliliter (pg*hr/mL)
Day 1 Number Analyzed 37 participants
54200
(42%)
Day 22 Number Analyzed 30 participants
209000
(36%)
Day 22 Subpopulation Number Analyzed 27 participants
208000
(37%)
16.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Plasma Talazoparib on Day 1 and Day 22
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: picogram/milliliter (pg/mL)
Day 1 Number Analyzed 37 participants
4350
(47%)
Day 22 Number Analyzed 30 participants
16300
(32%)
Day 22 Subpopulation Number Analyzed 27 participants
16400
(32%)
17.Secondary Outcome
Title Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter.
Arm/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Median (Full Range)
Unit of Measure: hour (hr)
Day 1 Number Analyzed 37 participants
2.00
(0.92 to 6.00)
Day 22 Number Analyzed 30 participants
2.00
(0.97 to 6.00)
Day 22 Subpopulation Number Analyzed 27 participants
2.00
(0.97 to 6.00)
18.Secondary Outcome
Title Predose Concentration (Ctrough) of Plasma Talazoparib on Day 22
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis population: all participants who had sufficient concentration data to derive at least 1 PK parameter.
Arm/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: pg/mL
Day 22 Number Analyzed 30 participants
4990
(53%)
Day 22 Subpopulation Number Analyzed 27 participants
4950
(56%)
19.Secondary Outcome
Title Apparent Clearance After Oral Dose (CL/F) of Plasma Talazoparib on Day 22
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liter/hour (L/hr)
Day 22 Number Analyzed 30 participants
4.8
(36%)
Day 22 Subpopulation Number Analyzed 27 participants
4.8
(37%)
20.Secondary Outcome
Title Accumulation Ratio (Rac) of Plasma Talazoparib on Day 22
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description:
Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
Overall Number of Participants Analyzed 37
Median (Full Range)
Unit of Measure: ratio
Day 22 Number Analyzed 30 participants
3.96
(1.89 to 14.4)
Day 22 Subpopulation Number Analyzed 27 participants
3.98
(1.89 to 14.4)
Time Frame Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Talazoparib 1 mg QD
Hide Arm/Group Description Talazoparib capsule was administered orally at 1 mg once daily (QD) for up to 22 days.
All-Cause Mortality
Talazoparib 1 mg QD
Affected / at Risk (%)
Total   0/37 (0.00%) 
Hide Serious Adverse Events
Talazoparib 1 mg QD
Affected / at Risk (%)
Total   3/37 (8.11%) 
Blood and lymphatic system disorders   
Anaemia * 1  1/37 (2.70%) 
Spontaneous Haemorrhage * 1  1/37 (2.70%) 
Gastrointestinal disorders   
Large intestinal obstruction * 1  1/37 (2.70%) 
Injury, poisoning and procedural complications   
Toxicity to various agents * 1  1/37 (2.70%) 
Nervous system disorders   
Syncope * 1  1/37 (2.70%) 
1
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Talazoparib 1 mg QD
Affected / at Risk (%)
Total   23/37 (62.16%) 
Blood and lymphatic system disorders   
Anaemia * 1  4/37 (10.81%) 
Thrombocytopenia * 1  3/37 (8.11%) 
Gastrointestinal disorders   
Abdominal pain upper * 1  3/37 (8.11%) 
Constipation * 1  3/37 (8.11%) 
Diarrhoea * 1  5/37 (13.51%) 
Nausea * 1  8/37 (21.62%) 
Vomiting * 1  4/37 (10.81%) 
General disorders   
Fatigue * 1  9/37 (24.32%) 
Investigations   
Platelet count decreased * 1  3/37 (8.11%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  2/37 (5.41%) 
Nervous system disorders   
Headache * 1  3/37 (8.11%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  3/37 (8.11%) 
1
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03042910    
Other Study ID Numbers: MDV3800-14
C3441005 ( Other Identifier: Alias Study Number )
First Submitted: December 22, 2016
First Posted: February 3, 2017
Results First Submitted: May 24, 2018
Results First Posted: December 17, 2019
Last Update Posted: December 17, 2019