Clinical trial NCT03042910
Conditions: Solid Tumor
Sponsor: Pfizer
Start date: 2016-10-13; Completion date: 2017-06-22
Enrollment: 38 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: Talazoparib 1 mg daily
Interventions: intervention 1: Talazoparib
Intervention descriptions: intervention 1: Talazoparib 1 mg orally once daily.

Protocol documents:
Prot_000.pdf: 
Medivation, Inc. 
CLINICAL RESEARCH PROTOCOL 
Study Title: 
A Phase 1, Open-Label Study to Assess the Effects of 
Talazoparib on Cardiac Repolarization in Patients With 
Advanced Solid Tumors 
Protocol Identifiers: 
MDV3800-14 
TRIO029 
Phase 
1 
Investigational Product: 
Talazoparib (also known as MDV3800, BMN 673) 
Indication: 
Solid Tumors 
Sponsor: 
Medivation, Inc. and its Subsidiaries 
525 Market Street, 36th Floor 
San Francisco, CA 94105 
Telephone: +1 (415) 543-3470 
Fax: 
+1 (415) 543-3411 
Reference Numbers: 
United States IND 108,708 
Sponsor Medical Monitor: 
. 
, MD 
Telephone: 
 
Mobile:  
 
Email: 
 
 
 
Original Protocol: 
v1.0 – 15 May 2016 
Amendment 1 
v2.0 – 19 Aug 2016 
 
 
 
 
 
 
 
 
 
 
 
 
This study will be conducted according to the principles of Good Clinical Practice as described in 
International Conference on Harmonisation guidelines, including the archiving of essential documents. 
 
 
 
 
 
 
 
 
PPD
PPD
PPD


Medivation, Inc. 
Talazoparib 
Protocol MDV3800-14/TRIO029 
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SYNOPSIS 
Title of Study:  A Phase 1, Open-Label Study to Assess the Effects of Talazoparib on Cardiac 
Repolarization in Patients With Advanced Solid Tumors 
Protocol Identifier:  MDV3800-14 
Phase of Development:  1 
Number of Patients:  At least 30 patients 
Study Centers:  Approximately 12 (United States) 
Study Objectives: 
Primary: 
• To evaluate the effect of talazoparib on cardiac repolarization in patients with advanced solid tumors 
by assessing the corrected QT interval (QTc) 
• To assess the relationship between plasma talazoparib concentrations and the QTc 
Secondary: 
• To evaluate the safety and tolerability of talazoparib 
• To evaluate the effect of talazoparib on non-QT interval electrocardiogram (ECG) parameters (heart 
rate, RR, PR, QRS intervals, and ECG morphology) 
• To evaluate the pharmacokinetics (PK) of talazoparib 
Methods:  This is a phase 1, open-label safety study of talazoparib (also known as MDV3800, BMN 673), 
a poly(ADP-ribose) polymerase (PARP) inhibitor in development for the treatment of a variety of human 
cancers.  This study is designed to evaluate the effects of talazoparib on cardiac repolarization in at least 
30 patients with advanced solid tumors with no available standard treatment options.  Eligible patients will 
have continuous 12-lead ECG recordings at baseline (day -1); time-matched PK samples and continuous 
ECG recordings will be obtained at days 1, 2, and 22.  Patients will fast for at least 6 hours before and 
2 hours after the dose on days 1 and 22.   
On day -1, patients will have continuous 12-lead ECG recording, starting at time 0 (baseline, corresponding 
to the dosing time on day 1) for 6 hours.  On day 1, continuous 12-lead ECG recording will start 45 minutes 
before administration of talazoparib 1 mg at time 0, and continue through 6 hours postdose.  Blood samples 
for PK will be collected predose and at 1, 2, 4, and 6 hours postdose.  On day 2, a 30-minute continuous 
12-lead ECG recording and a blood sample for PK will be obtained before the day 2 dose of talazoparib.   
On days 3 to 21, talazoparib at 1 mg/day every day will be self-administered orally.  On days 8 and 15, 
patients will return for general assessments.   
On day 22, patients will return for steady-state continuous 12-lead ECG recordings, starting 45 minutes 
before the dose of talazoparib, and continuing for 6 hours postdose.  PK samples will be collected predose 
and at 1, 2, 4, and 6 hours postdose.   
ECG data from continuous 12-lead ECG recordings will be submitted for independent central review.  After 
reviewing for data quality, triplicate 10-second ECGs will be extracted from a 5-minute extraction window at 
each planned time point, beginning 15 minutes before each PK collection time point.  ECG recordings will 
be analyzed for measurement of RR, PR, QRS, and QT intervals and evaluation of ECG morphology.   
Study periods include screening, baseline (day -1), a 22-day treatment period, and safety follow-up.  Safety 
follow-up will occur approximately 30 days after the last dose of study drug or before initiation of a new 
antineoplastic therapy, whichever occurs first.  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, and in this case, safety follow-up will be omitted and an ECG will be obtained at the time 
of enrollment in the open-label extension study.   


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Study Assessments:   
Continuous ECGs will be collected on days -1, 1, 2, and 22; single ECGs will be collected at screening and 
safety follow-up.  PK samples will be collected on days 1, 2, and 22.  Other general and laboratory 
assessments will be performed at screening; days -1, 1, 2, 8, 15, and 22; and safety follow-up according to 
the schedules of activities.  Safety will be assessed by adverse events, physical examinations, vital signs, 
ECGs, and clinical laboratory tests.   
No efficacy assessments will be performed for this study.  Disease assessments will be performed according 
to the standard of care at the study site.   
Study Schematic:   
  
[1] Safety follow-up will be omitted for patients who enroll and initiate continued talazoparib treatment within 30 days 
in the open-label extension study; an ECG will be obtained at the time of enrollment in the open-label extension 
study.   
Key Eligibility Criteria:   
Patients must have histologically confirmed advanced solid tumors with no available standard treatment 
options.  The Eastern Cooperative Oncology Group (ECOG) performance status score must be ≤ 2 and 
estimated life expectancy must be ≥ 3 months.   
Test Product, Dose, and Mode of Administration: 
Talazoparib is provided as the 4-methylbenzenesulfonate (tosylate) salt and has the chemical name (8S,9R) 
5-fluoro-8-(4-fluorophenyl)-2,7,8,9-tetrahydro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3H-
pyrido[4,3,2-de]phthalazin-3-one.   
The drug product is a capsule containing talazoparib tosylate and silicified microcrystalline cellulose.  The 
capsules for each dose strength will be provided in dose-specific colors.   
Talazoparib 1 mg will be self-administered orally once daily at approximately the same time each day.  
Talazoparib capsules will be swallowed whole with a glass of water.  Patients will fast for at least 6 hours 
before and 2 hours after the dose on days 1 and 22.  Patients may resume eating after the 2-hour postdose PK 
sample is collected.  On other days, talazoparib may be taken with or without food.   
Reference Therapy, Dose, and Mode of Administration: 
Not applicable.   
Duration of Treatment: 
Talazoparib treatment will continue through day 22 in this study.  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 talazoparib.  Dose modification guidelines must be followed for managing 
adverse events as described in Section 8.2.1.  Study drug treatment may be discontinued for disease 
progression based on investigator assessment.   
day -1
(baseline)
day 1
day 22
Talazoparib 1 mg daily 
days 1-22
Safety 
follow-up [1]
30 days after 
last dose
Screening
Patients with 
advanced solid tumors 
(N = 30)
Informed consent
Electrocardiograms 
↑           ↑            ↑                                                              ↑
day 2
Pharmacokinetics  
↑         
↑               
↑
day 15
day 8
Continue 
talazoparib in 
open-label 
extension study


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Protocol MDV3800-14/TRIO029 
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Statistical Methods: 
Safety Analyses:   
All safety analyses will be performed using the safety population, defined as all patients who receive any 
amount of talazoparib.  The safety of talazoparib will be evaluated by the analysis of incidence of serious and 
nonserious adverse events, severity of adverse events, incidence of dose modifications and of permanent 
treatment discontinuation due to adverse events, and incidence of new clinically significant changes in vital 
signs, ECGs, and clinical laboratory values.  Drug exposure will be summarized using descriptive statistics.   
Adverse events will be coded to preferred term and system organ class using the Medical Dictionary for 
Regulatory Activities (MedDRA) and classified by severity using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (CTCAE), version 4.  The number and percentage of patients with 
adverse events will be presented by MedDRA system organ class and preferred term, relationship to study 
treatment, severity, seriousness, and outcome (eg, leading to permanent treatment discontinuation).   
Treatment-emergent safety data will be collected from day 1 (the first dose of study drug) through 
approximately 30 days after the last dose of study drug, before initiation of a new antineoplastic therapy, or 
enrollment in the open-label extension study, whichever occurs first.   
Laboratory values will be classified by severity using the CTCAE.  Laboratory shift tables of baseline results 
to each subsequent visit will be produced as appropriate.   
ECG Analyses:  The primary endpoints are to evaluate the effects of talazoparib on Fridericia’s corrected QT 
interval (QTcF); and to evaluate the relationship between the plasma concentration of talazoparib and the 
change from baseline in QTc, corrected for heart rate based on Fridericia’s correction formula (ΔQTcF).  
Bazett’s correction formula (ΔQTcB) will also be evaluated.  Changes from time-matched baseline 
measurements will be calculated and data will be summarized in tabular and graphic formats for each study 
visit.  Assessments include absolute QTc prolongation with QTc > 450 msec, > 480 msec, and > 500 msec 
and change from baseline in QTc with QTc increase > 30 msec and > 60 msec.  The means of each 
measurement of RR, PR, QRS, and QT intervals will be utilized for statistical analyses.  Heart rate will be 
used to assess QTc endpoints.   
ECG morphology and changes from baseline for each planned postbaseline time point will be summarized 
for all patients.  The proportion of patients with any postbaseline change in ECG morphology and the 
proportion of patients with each type of abnormality will also be summarized.   
PK Analyses:   
Summary data of plasma talazoparib concentrations will be presented in tabular and graphic formats for each 
time point.  PK parameters such as time to maximum concentration (Tmax), maximum plasma concentration 
(Cmax), and area under the concentration-time curve (AUC) on days 1 and 22 will be calculated.  In addition, 
the PK data from this study will be combined with PK data from other studies to define a population PK 
model, which will be reported separately.   
PK-Pharmacodynamic Analyses: 
The correlation between changes in ECG interval measurements from time-matched baseline and the plasma 
talazoparib concentration will be investigated using a linear mixed-effects model.   
Efficacy Analyses:   
No efficacy analysis is planned in this study.   
Sample Size Considerations:   
A sample size of at least 30 evaluable patients will provide 80% power to reject the null hypothesis if the 
mean change from baseline in QTcF is ≥ 10 msec with a 95% one-sided alpha, assuming a standard deviation 
of 20 msec.  Patients will be enrolled until 30 patients complete day 22, miss ≤ 5 consecutive doses of study 
drug, have technically adequate ECG recordings, and have at least 80% of specified PK samples collected 
representing all 3 days of observation (days 1, 2, and 22).   
 


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TABLE OF CONTENTS 
SYNOPSIS ............................................................................................................................................................ 2 
LIST OF ABBREVIATIONS AND TERMS ..................................................................................................... 8 
1 INTRODUCTION .......................................................................................................................................... 9 
1.1 Background .............................................................................................................................................. 9 
1.2 Summary of Relevant Clinical Experience With Talazoparib ................................................................. 9 
1.2.1 Efficacy ......................................................................................................................................... 9 
1.2.2 Safety .......................................................................................................................................... 10 
1.2.3 Pharmacokinetics ........................................................................................................................ 10 
1.3 Summary of Relevant Nonclinical Experience With Talazoparib.......................................................... 11 
1.3.1 Nonclinical Pharmacology of Talazoparib ................................................................................. 11 
1.3.2 Nonclinical PK and Metabolism ................................................................................................. 12 
1.3.3 Nonclinical Toxicology .............................................................................................................. 13 
1.4 Cardiac Safety of Talazoparib ................................................................................................................ 14 
1.5 Talazoparib Benefits and Risks Assessment .......................................................................................... 15 
2 STUDY OBJECTIVES ................................................................................................................................ 15 
2.1 Primary Objectives ................................................................................................................................. 15 
2.2 Secondary Objectives ............................................................................................................................. 15 
3 INVESTIGATIONAL PLAN ...................................................................................................................... 15 
3.1 Overall Study Design and Plan:  Description ......................................................................................... 15 
3.2 Study Schematic ..................................................................................................................................... 16 
3.3 Blinding .................................................................................................................................................. 17 
3.4 Duration of Study ................................................................................................................................... 17 
3.5 Discussion of Study Design ................................................................................................................... 17 
4 SELECTION OF STUDY POPULATION ................................................................................................. 18 
4.1 Inclusion Criteria .................................................................................................................................... 18 
4.2 Exclusion Criteria ................................................................................................................................... 18 
5 ENROLLMENT AND STUDY PROCEDURES ....................................................................................... 20 
5.1 Screening Period .................................................................................................................................... 20 
5.1.1 Informed Consent ....................................................................................................................... 20 
5.1.2 Screening Identification Numbers .............................................................................................. 20 
5.1.3 Screening Procedures .................................................................................................................. 21 
5.2 Treatment Period .................................................................................................................................... 21 
5.2.1 Treatment Period Visit Windows................................................................................................ 21 
5.2.2 Treatment Period Procedures ...................................................................................................... 21 
5.2.2.1 Enrollment .................................................................................................................... 21 
5.2.2.2 Treatment Period Study Visit Procedures ..................................................................... 21 
5.2.3 Unscheduled Visit Procedures .................................................................................................... 22 
5.3 Permanent Treatment Discontinuation ................................................................................................... 22 
5.4 Safety Follow-Up ................................................................................................................................... 23 
5.5 Loss to Follow-Up .................................................................................................................................. 24 
6 INVESTIGATIONAL PRODUCT INFORMATION ............................................................................... 24 
6.1 General Information ............................................................................................................................... 24 
6.2 Talazoparib Product Characteristics ....................................................................................................... 24 
6.2.1 Packaging of Talazoparib ........................................................................................................... 24 
6.2.2 Storage of Talazoparib ................................................................................................................ 25 


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6.2.3 Directions for Administration of Talazoparib ............................................................................. 25 
6.3 Treatment Compliance ........................................................................................................................... 25 
7 PRIOR AND CONCOMITANT THERAPY ............................................................................................. 25 
7.1 Prior Medications ................................................................................................................................... 26 
7.2 Concomitant Therapy ............................................................................................................................. 26 
7.3 Potential Interactions Between Talazoparib and Concomitant Medications .......................................... 27 
8 SAFETY CONSIDERATIONS ................................................................................................................... 27 
8.1 Safety Monitoring .................................................................................................................................. 27 
8.2 Special Safety Considerations ................................................................................................................ 27 
8.2.1 Dose Modification Due to Adverse Events ................................................................................. 27 
8.2.1.1 Assessment of Abnormal Liver Tests ........................................................................... 29 
8.2.2 Overdose Management ............................................................................................................... 33 
8.2.3 Reproductive Considerations ...................................................................................................... 33 
8.3 Adverse Event Definitions and Reporting .............................................................................................. 34 
8.3.1 Adverse Event Definitions .......................................................................................................... 34 
8.3.2 Adverse Event Reporting ............................................................................................................ 36 
8.3.2.1 Adverse Event Reporting Periods ................................................................................. 36 
8.3.3 Assessment of Causal Relationship ............................................................................................ 37 
8.3.4 Assessment of Severity (Intensity) ............................................................................................. 38 
8.3.5 Adverse Events of Special Interest ............................................................................................. 38 
8.3.6 Serious Adverse Event Reporting ............................................................................................... 39 
8.3.7 Clarification in Reporting of Deaths ........................................................................................... 40 
8.3.8 Clarification in Reporting of Disease Progression as an Adverse Event Term ........................... 40 
8.3.9 Follow-Up of Serious and Nonserious Adverse Events .............................................................. 40 
8.3.10 Pregnancy Reporting Procedure ................................................................................................. 40 
8.4 Clinical Laboratory Tests ....................................................................................................................... 41 
8.5 Physical Examinations, Vital Signs, and ECGs ..................................................................................... 42 
9 ASSESSMENT OF SAFETY, PHARMACOKINETIC, AND EFFICACY ENDPOINTS.................... 42 
9.1 Assessment of Safety ............................................................................................................................. 42 
9.2 Assessment of QTc ................................................................................................................................ 42 
9.3 Assessment of PK .................................................................................................................................. 43 
9.4 ECOG Performance Status ..................................................................................................................... 43 
9.5 Assessment of Efficacy .......................................................................................................................... 43 
10 STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION ............................................... 43 
10.1 Statistical and Analytical Plans .............................................................................................................. 43 
10.2 Analysis Populations .............................................................................................................................. 43 
10.3 Safety Analyses ...................................................................................................................................... 44 
10.4 ECG Analyses ........................................................................................................................................ 44 
10.5 PK Analyses ........................................................................................................................................... 45 
10.6 PK-PD Analyses..................................................................................................................................... 45 
10.7 Efficacy Analyses ................................................................................................................................... 45 
10.8 Determination of Sample Size ................................................................................................................ 45 
11 STUDY COMMITTEES AND COMMUNICATIONS ............................................................................ 45 
12 LABORATORY REQUIREMENTS .......................................................................................................... 46 
13 INVESTIGATOR AND ADMINISTRATIVE REQUIREMENTS ......................................................... 46 
13.1 Ethics ...................................................................................................................................................... 46 
13.1.1 Ethics Committee ........................................................................................................................ 46 


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13.1.2 Ethical Conduct of the Study ...................................................................................................... 47 
13.1.3 Patient Information and Informed Consent ................................................................................. 47 
13.1.4 Maintaining Patient Confidentiality ............................................................................................ 47 
13.2 Data Quality Assurance .......................................................................................................................... 48 
13.2.1 Data Management ....................................................................................................................... 48 
13.2.2 Case Report Forms ..................................................................................................................... 48 
13.2.3 Study Monitoring ........................................................................................................................ 48 
13.2.4 Study Audits ............................................................................................................................... 49 
13.3 Investigational Product Accountability .................................................................................................. 49 
13.4 Compensation, Insurance, and Indemnity .............................................................................................. 50 
13.5 Retention of Records .............................................................................................................................. 50 
13.6 Study Termination .................................................................................................................................. 51 
14 USE OF STUDY INFORMATION AND PUBLICATION ...................................................................... 51 
15 REFERENCES ............................................................................................................................................. 53 
16 INVESTIGATOR SIGNATURE ................................................................................................................. 54 
 
LIST OF TABLES 
Table 1: 
Primary Reasons for Permanent Treatment Discontinuation ......................................................... 23 
Table 2: 
Prohibited Concomitant Therapies ................................................................................................ 26 
Table 3: 
Dose Modification of Study Drug Due to Adverse Events ............................................................ 28 
Table 4: 
Talazoparib Dose Reductions for Toxicity .................................................................................... 29 
Table 5: 
Criteria for Temporary Withholding of Study Drug in Association With Liver Test 
Abnormalities ................................................................................................................................ 30 
Table 6: 
Investigations of Alternative Causes for Abnormal Liver Tests .................................................... 31 
Table 7: 
Monitoring of Liver Tests for Potential Drug-Induced Liver Injury ............................................. 32 
Table 8: 
Criteria for Serious Adverse Events .............................................................................................. 35 
Table 9: 
Criteria for Determining Causal Relationship to Study Drug ........................................................ 37 
Table 10: 
Criteria for Determining the Severity (Intensity) of an Adverse Event for Terms Not Specified 
in CTCAE ...................................................................................................................................... 38 
Table 11: 
Central Laboratory Tests ............................................................................................................... 41 
Table 12: 
ECOG Performance Status ............................................................................................................ 43 
 
LIST OF FIGURES 
Figure 1: 
Study Schematic ............................................................................................................................ 16 
Figure 2: 
Adverse Event Reporting Periods .................................................................................................. 37 
 
LIST OF APPENDICES 
Appendix 1: Study Schedule of Activities:  Screening ...................................................................................... 55 
Appendix 2: Study Schedule of Activities:  Treatment ...................................................................................... 56 
Appendix 3: Time Points for ECG, Blood Pressure, and PK Assessments ........................................................ 58 
 


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LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Definition 
ALT 
Alanine aminotransferase 
AML 
Acute myeloid leukemia 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
BRCA 
Breast cancer susceptibility gene 
BCRP 
Breast cancer resistance protein 
CFR 
Code of Federal Regulations 
CL/F 
Apparent oral clearance 
Cmax 
Maximum plasma concentration 
Cmin 
Plasma trough concentration 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP450 
Cytochrome P450 
EC 
Ethics committee (global term including institutional review boards, independent 
ethics committees, research ethics committees, and the like) 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
IC50 
Half-maximal inhibitory concentration 
ICH 
International Conference on Harmonisation 
ID 
Identification 
INR 
International normalized ratio 
MDS 
Myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
PARP 
Poly(ADP-ribose) polymerase 
P-gp 
P-glycoprotein 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
QTc 
Corrected QT interval 
QTcB 
Bazett’s corrected QT interval 
QTcF 
Fridericia’s corrected QT interval 
SUSAR 
Suspected unexpected serious adverse reaction 
Tmax 
Time to maximum plasma concentration 
ULN 
Upper limit of normal 
US 
United States 
 


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1 INTRODUCTION 
1.1 
Background 
Talazoparib (also known as MDV3800, BMN 673) is a potent, orally bioavailable, small 
molecule poly(ADP-ribose) polymerase (PARP) inhibitor in development for the treatment 
of a variety of human cancers.  PARP inhibitors including talazoparib exert cytotoxic effects 
by 2 mechanisms:  inhibition of PARP1 and PARP2 enzyme activity, and PARP trapping, 
a process in which PARP protein bound to a PARP inhibitor does not readily dissociate from 
DNA, preventing DNA repair, replication, and transcription (Murai et al, 2012).  
Single-agent talazoparib has demonstrated potent antitumor effects in human cancer cell lines 
harboring gene mutations that compromise DNA repair, as well as in mouse tumor xenograft 
models (Murai et al, 2014; Shen et al, 2013; Cardnell et al, 2013).  Antitumor effects have 
also been observed in phase 1 studies of talazoparib monotherapy in patients with cancer.   
This cardiac safety study will evaluate the effects of talazoparib on cardiac 
electrophysiology, in particular cardiac repolarization as assessed by the corrected QT 
interval (QTc).   
1.2 
Summary of Relevant Clinical Experience With Talazoparib 
Approximately 319 patients have received talazoparib in company-sponsored studies as of 
30 Nov 2015, including 3 studies in solid tumors and 1 in hematologic malignancies.  Studies 
include a phase 1 study (PRP-001) in advanced solid tumors, a phase 2 study (673-201, 
ABRAZO) in advanced breast cancer, and a phase 3 study (673-301, EMBRACA) in locally 
advanced and/or metastatic breast cancer.   
1.2.1 
Efficacy 
PRP-001 is a phase 1, open-label, safety, pharmacokinetics (PK), and dose-escalation 
(0.025-1.1 mg/day) and expansion (1 mg/day) study of talazoparib monotherapy 
in 110 patients with advanced or recurrent solid tumors with DNA repair deficiencies.  As of 
30 Nov 2015, objective responses (complete response, partial response) per Response 
Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) were observed in patients 
with breast (8 of 18 [44.4%]), ovarian/primary peritoneal (12 of 25 [48%]), and pancreatic 
(2 of 13 [15.4%]) cancers with deleterious germline breast cancer susceptibility gene 
(BRCA) mutations.  Clinical benefit (complete response, partial response, or stable disease 
≥ 24 weeks) was observed in 13 of 18 patients (72.2%), 19 of 25 patients (76%), and 4 of 
13 patients (30.8%), respectively.  In patients with small cell lung cancer, objective responses 
were observed in 2 of 23 patients (8.7%) and clinical benefit reported in 6 of 23 patients 
(26.1%).   
Additional information on the clinical efficacy of talazoparib is provided in the talazoparib 
investigator brochure.   


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1.2.2 
Safety 
The safety of talazoparib is based on phase 1 and 2 studies in patients with advanced cancer.   
Aggregate safety data from 3 of the 5 company-sponsored clinical studies (phase 1 studies 
PRP-001 and PRP-002, and phase 2 study 673-201; 214 patients total; data as of 
30 Nov 2015) provide the basis for the most common treatment-emergent adverse events.  
The most common adverse events associated with talazoparib (> 20%) were 
myelosuppression (anemia, thrombocytopenia, neutropenia), gastrointestinal toxicity (nausea, 
diarrhea, vomiting), and fatigue.  The most common grade 3 or higher adverse events and 
serious adverse events were associated with myelosuppression.  A total of 25 of 214 patients 
had an adverse event that led to death (12 associated with malignancies, 3 disease 
progression, 2 each lung infection and pneumonia, and 1 each cardiorespiratory arrest, 
neutropenic sepsis, renal impairment, dyspnea, hypoxia, and respiratory failure).  Of these 
events, none was assessed as related to study drug.  Eight of 214 patients discontinued study 
drug due to an adverse event.   
In the ongoing phase 3 study 673-301, an adverse event of veno-occlusive disease of the liver 
leading to death was assessed as related to talazoparib by the investigator.   
Additional information on the clinical safety of talazoparib is provided in the talazoparib 
investigator brochure.   
1.2.3 
Pharmacokinetics 
The PK of talazoparib as a single agent was evaluated in 142 adult patients with cancer, 
including 109 patients with solid tumors (PRP-001) and 33 with hematologic malignancies 
(PRP-002).  Doses of 0.025 mg to 2 mg were administered orally as a single dose or as 
once daily doses.  This dose range bracketed the 1 mg/day dose used in ongoing safety and 
efficacy studies, and provided a framework for assessing dose linearity.  As the PK of 
talazoparib was similar in patients with solid tumors and hematologic malignancies, and no 
differences were apparent between males and females, the results are summarized 
collectively.   
Oral absorption of talazoparib was rapid and independent of dose after administration of 
single or once-daily doses.  Peak talazoparib concentrations were generally reached 
approximately 1 to 8 hours postdose.  Exposure increased approximately dose-proportionally 
with increasing doses.  At 1 mg/day, the mean half-life was approximately 2 days; the mean 
apparent volume of distribution was 415 L, indicating extensive extravascular distribution.  
Steady state was reached in approximately 2 to 3 weeks with daily administration.   
Apparent oral clearance (CL/F) of talazoparib appeared to be dose linear, with a mean CL/F 
across doses of approximately 5 L/h.  Renal excretion was a major elimination pathway for 
unchanged parent talazoparib.  Following oral administration, 44% to 90.6% of the dose was 
recovered in urine as unchanged parent drug over 24 hours at steady state for doses up to 
1 mg/day.  Mean renal clearance ranged from 1.38 L/h to 4.96 L/h, independent of dose, 
suggesting linear urinary elimination kinetics.   


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Following repeated administration at 1 mg/day, talazoparib accumulated approximately 
2.4-fold relative to a single dose.  At steady state, the mean maximum plasma concentration 
(Cmax) was 21.0 ng/mL, the mean plasma trough concentration (Cmin) was 3.72 ng/mL, and 
the mean area under the concentration-time curve (AUC) was 202 ng●h/mL.   
PK data from a food-effect study showed that food had no effect on the extent of absorption 
of talazoparib (AUC), but decreased the rate of absorption (Cmax was 46% lower and time to 
Cmax [Tmax] was 2.63 hours later); however this reduction in the rate of absorption following 
a single dose is not clinically relevant because talazoparib accumulates 2.4-fold at steady 
state after 1 mg once-daily dosing.  Furthermore, in nonclinical pharmacology studies, AUC 
or Cmin appeared to drive efficacy, not Cmax; therefore, talazoparib can be taken with or 
without food.  Talazoparib is being administered without regard to food in ongoing safety 
and efficacy studies.   
A preliminary population PK analysis using data from patients in studies PRP-001 and 
PRP-002 assessed the effects of renal function on the PK of talazoparib.  In patients with 
moderate renal impairment (creatinine clearance [CLCR] 30-59 mL/min), the talazoparib 
CL/F was decreased by 44% from normal, resulting in higher talazoparib exposure.   
The effects of hepatic impairment on talazoparib PK have not been studied.   
The potential for talazoparib to affect the PK of other drugs was assessed through in vitro 
experiments and is described in Section 1.3.2.  Additional information on the PK of 
talazoparib is provided in the investigator brochure.   
1.3 
Summary of Relevant Nonclinical Experience With Talazoparib 
1.3.1 
Nonclinical Pharmacology of Talazoparib 
The cytotoxic activity of talazoparib was demonstrated in cell culture, and antitumor effects 
were demonstrated in mouse xenograft models.   
In cell-free enzyme assays, talazoparib inhibited PARP1 and PARP2 catalytic activity 
(Wang et al, 2016).  Talazoparib was approximately 3.4- to 8.3-fold more potent than other 
PARP inhibitors in clinical development (veliparib, rucaparib, olaparib) in inhibiting PARP1 
catalytic activity (Shen et al, 2013).  In addition, talazoparib was approximately 40-fold more 
potent than olaparib in stimulating the formation of stable PARP1-DNA complexes 
(Murai et al, 2014).   
In tissue culture studies, talazoparib was cytotoxic to cancer cell lines harboring gene 
mutations that compromise DNA repair pathways, including MX-1 (BRCA1-mutant) and 
MDA-MB-468 (PTEN-mutant) mammary cancer cells, LNCaP (PTEN- and ATM-mutant) 
and PC-3 (PTEN-mutant) prostate cancer cells, and HCT-116 (MLH-1-mutant) colorectal 
tumor cells.  The half-maximal inhibitory concentration (IC50) values of talazoparib in these 
cancer cell lines were in the single-digit nanomolar or subnanomolar range; in contrast, the 
IC50 values of talazoparib in MRC-5 normal human primary lung cancer cells and other 
tumor cell lines without reported DNA repair-related mutations were higher (250 nM to 


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> 1000 nM).  The talazoparib IC50 for growth inhibition of Capan-1 human pancreatic cancer 
cells (BRCA2-deficient) was 50- to over 2000-fold lower than the other PARP inhibitors 
tested (Shen et al, 2013).  The higher potency of talazoparib relative to the other PARP 
inhibitors is thought to be due to the more potent PARP trapping activity seen with 
talazoparib as opposed to inhibition of PARP catalytic activity (Shen et al, 2015).   
Consistent with its antitumor effects in tissue culture, talazoparib demonstrated potent 
antitumor activity in mouse xenograft models of small cell lung cancer and breast cancer 
(Cardnell et al, 2013; Shen et al, 2013).   
Additional information on the nonclinical pharmacology of talazoparib is provided in the 
talazoparib investigator brochure.   
1.3.2 
Nonclinical PK and Metabolism 
PK studies in rats and dogs show that talazoparib oral bioavailability was > 43% in rats and 
> 51% in dogs.  A Good Laboratory Practice (GLP) study in dogs demonstrated that the 
capsule formulation used in clinical studies is approximately 2-fold more bioavailable than 
the suspension formulation used in nonclinical studies.  In general, talazoparib displays 
greater than or approximately dose-proportional increases in exposure in rats and dogs with 
no evidence of sex differences.   
Studies of [14C]-talazoparib in rats and dogs indicate rapid absorption, wide distribution 
(greater than total body water), and nearly complete elimination of drug substance (> 90%) 
by 7 days.  Fecal elimination was the main route of elimination in both species, and renal 
excretion was moderate (21-26%).  In a study in rats, [14C]-talazoparib was widely 
distributed, reaching maximum levels 1 to 4 hours postdose.  Excluding the gastrointestinal 
tract, the highest radioactivity levels were observed in liver and kidney (and the eye uveal 
tract in albino rats).  Tissue radioactivity levels were greater than blood levels in the target 
organs of talazoparib toxicity (bone marrow, spleen, and thymus) through 7 days.  Metabolic 
profiling of plasma, urine, and feces samples indicated that [14C]-talazoparib is largely 
cleared via excretion of unchanged parent drug and metabolized to a minor extent via 
oxidation and dehydrogenation.   
In vitro metabolism studies in rat, dog, and human hepatic microsomes demonstrated that 
[14C]-talazoparib has high metabolic stability (> 90%) over 2 hours.  A minimal extent or 
a lack of metabolism for [14C]-talazoparib was observed in the presence of freshly isolated 
mouse, rat, dog, and human hepatocytes or cryopreserved human hepatocytes.  Talazoparib 
does not appear to be a substrate of any major cytochrome P450 (CYP450) metabolizing 
enzyme.   
Mean binding to human plasma proteins is 78.7%; therefore, it is unlikely that talazoparib 
will demonstrate clinically significant drug-drug interactions related to displacement from 
plasma protein binding sites.  At therapeutic exposures, talazoparib does not markedly induce 
or inhibit CYP450 enzymes.  Therefore, it is unlikely that talazoparib will demonstrate 
clinically significant CYP450 inhibition- or induction-based drug-drug interactions when 
coadministered with corresponding substrates.  At therapeutic exposures, talazoparib does 


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not markedly induce or inhibit any transporters.  Therefore, it is unlikely that talazoparib will 
demonstrate clinically significant drug transporter inhibition-based drug–drug interactions 
when coadministered with corresponding substrates.   
Because talazoparib is a substrate for P-glycoprotein (P-gp) and breast cancer resistance 
protein (BCRP), plasma talazoparib concentrations may increase or decrease when 
coadministered with P-gp or BCRP inhibitors or inducers, respectively.  Guidelines for 
concomitant use of talazoparib inhibitors or inducers of P-gp or inhibitors of BCRP are 
provided in Section 7.3.   
Additional information on the nonclinical PK and drug metabolism of talazoparib is provided 
in the investigator brochure.   
1.3.3 
Nonclinical Toxicology 
Safety pharmacology, single- and repeat-dose toxicity, genotoxicity, embryo-fetal 
development, and in vitro phototoxicity studies were conducted to evaluate the nonclinical 
toxicology profile of talazoparib.  Repeat-dose toxicity/toxicokinetic studies were conducted 
with talazoparib utilizing the intended oral route of administration in mice, rats, and dogs.  A 
repeat-dose study with talazoparib was conducted in BALB/c nude mice to select doses and 
exposures for the mouse xenograft studies.   
Five-day, 28-day, and 13-week repeat-dose GLP toxicity and toxicokinetic studies with 
28-day recovery periods were conducted in the rat and dog.  The major findings are as 
follows:   
• 
Dose-dependent pancytopenia with bone marrow hypocellularity and depletion of 
lymphoid tissue in multiple organs was observed and considered possibly due to 
exaggerated pharmacology of talazoparib based on the higher (relative to baseline) 
poly(ADP-ribose) (index of PARP1/2 activity) tissue levels in these organs.  The 
hematologic findings were partially reversible and may be readily monitored in the 
clinic.  The toxicities that resulted in mortality in dogs (0.1 mg/kg/day) and some rats 
(1 mg/kg/day) occurred at AUC0-24 exposures that were > 0.8- and 4-fold higher, 
respectively, than the exposure at the recommended human dose of 1 mg/day.  The 
toxicities were mainly due to septicemia that resulted from the severe bone marrow 
and lymphoid depletion.   
• 
A dose-dependent increased incidence of gastrointestinal tract findings of 
apoptosis/necrosis in the stomach and duodenum was observed.  Additional findings 
at higher doses included reversible villous atrophy and increased apoptosis 
throughout the gastrointestinal tract, most notably in the small intestine.  
Gastrointestinal tract toxicities of enteropathy and villous atrophy caused mortality in 
rats at 3.0 mg/kg/day.  Exposures at 3.0 mg/kg/day are significantly higher than the 
exposures at the recommended human dose.   


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• 
Additional findings at the high dose (≥ 1 mg/kg/day) in the 5-day GLP study in rats 
included focal necrotic changes in the ovarian follicular atresia and hepatocyte 
necrosis of the liver.  These findings were not observed in the 28-day or 13-week 
repeat-dose studies in rats.   
• 
Atrophy and/or degenerative changes in testes and epididymis and effects on the 
seminiferous tubules were observed in rats and dogs; the severity correlated with both 
dose and duration of treatment.   
There were no talazoparib-related effects on respiratory or central nervous system parameters 
after a single oral administration to rats (safety pharmacology studies), or on cardiovascular 
parameters and electrocardiogram (ECG) evaluations after a repeat-dose oral administration 
in dogs (repeat-dose toxicity studies).  Talazoparib had no effect on ophthalmologic end 
points in rats or dogs in repeat-dose toxicity studies.  Talazoparib was not mutagenic in a 
bacterial reverse mutation assay, but consistent with the genomic instability of its primary 
pharmacology, was clastogenic in an in vitro chromosomal aberration assay and in an in vivo 
micronucleus assay, indicating the potential for genotoxicity in humans.  Talazoparib caused 
fetal malformations, structural variations, and death in an embryo-fetal development study in 
rats.  Based on an in vitro 3T3 neutral red uptake assay, which results in a high incidence of 
false positives, talazoparib is potentially phototoxic in humans.  In conclusion, the main 
nonclinical toxicologic findings were early hematologic changes, and subsequent bone 
marrow and lymphoid organ depletion; focal atrophy and degeneration of testes, epididymis, 
and seminiferous tubules; and dose-dependent apoptosis/necrosis in the gastrointestinal tract 
and liver after repeat-dose talazoparib.  These findings are consistent with the exaggerated 
pharmacology of talazoparib and its tissue exposure pattern.  Additional information on the 
toxicology of talazoparib is provided in the talazoparib investigator brochure.   
1.4 
Cardiac Safety of Talazoparib 
In vitro, talazoparib has an estimated IC50 for inhibition of hERG channels of > 100 μM 
whereas in humans taking 1 mg once daily the mean Cmax at steady state is 0.055 μM (free 
Cmax of 0.0117 μM), indicating low potential for significant inhibition.  In vivo, ECG 
evaluations were conducted in 28-day and 13-week toxicity studies in beagle dogs over a 
range of doses.  No talazoparib-related changes in PR, QRS, QT, QTc, or RR intervals, or 
heart rate were observed on days 3 or 24 of the dosing phase (28-day study) or day 90 of the 
dosing phase or day 26 of the recovery phase (13-week study).  No rhythm abnormalities or 
qualitative ECG changes were observed during qualitative assessment of the ECGs in either 
study.   
In phase 1 study PRP-001 (110 patients), ECGs were recorded at baseline, at 3 to 4 hours 
postdose on days 1 and 35 (dose-escalation phase) or at day 1 of cycle 2 (dose-expansion 
phase), and at the end of treatment (< 10 days after the last dose of talazoparib), if clinically 
indicated.  ECG interval data were collected retrospectively from these recordings.  Of the 
96 patients with ECG recordings at baseline and postbaseline based on draft data, 1 patient 
had a postbaseline QTcF (Fridericia’s corrected QT interval) > 500 msec; 1 had a 
postbaseline QTcF > 480 msec to ≤ 500 msec; and 9 (9.4%) had a postbaseline 


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QTcF > 450 msec to ≤ 480 msec.  One patient had an increase in QTcF from baseline 
> 60 msec and 6 (6.3%) had an increase in QTcF from baseline > 30 msec to ≤ 60 msec.   
These observations indicate that talazoparib has a low risk of QT prolongation or 
proarrhythmic effects.  This study will further assess the effects of talazoparib on cardiac 
electrophysiology.   
1.5 
Talazoparib Benefits and Risks Assessment 
The dose of talazoparib in this study, 1 mg/day, is supported by nonclinical studies and 
phase 1 studies in patients with advanced malignancies.  Antitumor activity has been 
observed, and warrants further exploration in a larger patient population.  The expected 
adverse events with talazoparib include myelosuppression, gastrointestinal toxicity, fatigue, 
and alopecia.  Hepatotoxicity, febrile neutropenia, and neutropenic sepsis are potential risks 
per the investigator brochure Section 7.  The activity of talazoparib is being evaluated in 
multiple indications.  The benefit-risk profile of talazoparib is not yet well characterized.   
2 STUDY OBJECTIVES 
2.1 
Primary Objectives 
• 
To evaluate the effect of talazoparib on cardiac repolarization in patients with 
advanced solid tumors by assessing the QTc 
• 
To assess the relationship between plasma talazoparib concentrations and the QTc 
2.2 
Secondary Objectives 
• 
To evaluate the safety and tolerability of talazoparib 
• 
To evaluate the effect of talazoparib on non-QT interval ECG parameters (heart rate, 
RR, PR, QRS intervals, and ECG morphology) 
• 
To evaluate the PK of talazoparib 
3 INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan:  Description 
This is a phase 1, open-label safety study of talazoparib, a PARP inhibitor in development for 
the treatment of a variety of human cancers.  This study is designed to evaluate the effects of 
talazoparib on cardiac repolarization in at least 30 patients with advanced solid tumors with 
no available standard treatment options.  Eligible patients will have continuous 12-lead ECG 
recordings at baseline (day -1); time-matched PK samples and continuous ECG recordings 
will be obtained at days 1, 2, and 22.  Patients will fast for at least 6 hours before and 2 hours 
after the dose on days 1 and 22.   
On day -1, patients will have continuous 12-lead ECG recording, starting at time 0 (baseline, 
corresponding to the dosing time on day 1) for 6 hours.  On day 1, continuous 12-lead ECG 


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recording will start 45 minutes before administration of talazoparib 1 mg at time 0, and 
continue through 6 hours postdose.  Blood samples for PK will be collected predose and at 1, 
2, 4, and 6 hours postdose.  On day 2, a 30-minute continuous 12-lead ECG recording and a 
blood sample for PK will be obtained before the day 2 dose of talazoparib.   
On days 3 to 21, talazoparib at 1 mg/day every day will be self-administered orally.  On 
days 8 and 15, patients will return for general assessments.   
On day 22, patients will return for steady-state continuous 12-lead ECG recordings, starting 
45 minutes before the dose of talazoparib, and continuing for 6 hours postdose.  PK samples 
will be collected predose and at 1, 2, 4, and 6 hours postdose.   
ECG data from continuous 12-lead ECG recordings will be submitted for independent central 
review.  After reviewing for data quality, triplicate 10-second ECGs will be extracted from a 
5-minute extraction window at each planned time point, beginning 15 minutes before each 
PK collection time point.  ECG recordings will be analyzed for measurement of RR, PR, 
QRS, and QT intervals and evaluation of ECG morphology.   
Study periods include screening, baseline (day -1), a 22-day treatment period, and safety 
follow-up.  Safety follow-up will occur approximately 30 days after the last dose of study 
drug or before initiation of a new antineoplastic therapy, whichever occurs first.  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, and in 
this case, safety follow-up will be omitted and an ECG will be obtained at the time of 
enrollment in the open-label extension study.   
3.2 
Study Schematic 
The study schematic is provided in Figure 1.   
Figure 1: Study Schematic 
[1] Safety follow-up will be omitted for patients who enroll and initiate continued talazoparib treatment within 
30 days in the open-label extension study; an ECG will be obtained at the time of enrollment in the open-label 
extension study.   
 
day -1
(baseline)
day 1
day 22
Talazoparib 1 mg daily 
days 1-22
Safety 
follow-up [1]
30 days after 
last dose
Screening
Patients with 
advanced solid tumors 
(N = 30)
Informed consent
Electrocardiograms 
↑           ↑            ↑                                                              ↑
day 2
Pharmacokinetics  
↑         
↑               
↑
day 15
day 8
Continue 
talazoparib in 
open-label 
extension study


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3.3 
Blinding 
All treatments will be open label.  All patients, study site personnel (including investigators), 
and sponsor staff and its representatives will be unblinded to treatment identity.  Central 
reviewers for ECG data are blinded to patient identifiers, treatment, and visit.   
3.4 
Duration of Study 
The total duration of this study will be approximately 1 year.   
3.5 
Discussion of Study Design 
The maximum tolerated dose of talazoparib is 1 mg/day (de Bono et al, 2013) and is defined 
as the recommended human dose.  The talazoparib 1 mg/day dose is being used in this study 
and is currently being evaluated in ongoing studies in patients with breast cancer, as 
discussed in Section 1.  This study will assess the risk of QT prolongation with serial ECG 
recordings and time-matched PK measurements.  Supratherapeutic doses cannot be 
administered safely, so a traditional thorough QT study is not feasible.  Because talazoparib 
is clastogenic in vitro and in vivo, it is not possible to conduct the study in healthy 
volunteers.  Therefore, adult patients with advanced solid tumors, representative of the 
population being evaluated in current and planned phase 2 and 3 studies, will be enrolled.   
With chronic dosing at 1 mg/day, plasma talazoparib concentrations reach steady state in 
2 to 3 weeks, with about a 2.4-fold accumulation relative to a single dose.  Therefore, 
a 22-day dosing duration will allow most patients to reach steady-state concentrations of 
talazoparib.  ECG recordings will be obtained with time-matched PK samples over a wide 
range of plasma talazoparib concentrations, after both acute and chronic dosing.   
The primary endpoints are to evaluate the effects of talazoparib on QTcF and to evaluate the 
relationship between the plasma concentration of talazoparib and the change from baseline in 
QTc, corrected for heart rate based on the QTcF correction formula (∆QTcF).  Bazett’s 
correction formula (ΔQTcB) will also be evaluated.  Continuous ECG recordings will be 
obtained at baseline (day -1), and continuous ECG recordings and blood samples for PK will 
be obtained on days 1, 2, and 22 (steady state) to obtain ECG recordings over a range of 
plasma concentrations of talazoparib.  Patients will fast for at least 6 hours before and 
2 hours after the dose on days 1 and 22 to minimize the variability of Cmax.  For the PK-
pharmacodynamic (PD) analysis, a linear mixed effects modeling approach will be used to 
examine the relationship between the changes from baseline in QTc intervals (ΔQTcF and 
ΔQTcB) and plasma concentration of talazoparib.   
No tumor assessments or other efficacy measures will be collected in this study.  Disease 
assessments may be performed according to the standard of care at the study site.   


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4
SELECTION OF STUDY POPULATION 
The specific eligibility criteria for selection of patients are provided in Section 4.1 and 
Section 4.2.  The sponsor will not grant any eligibility waivers.   
4.1
Inclusion Criteria 
Each patient eligible to participate in this study must meet all of the following criteria: 
At least 18 years of age and willing and able to provide informed consent.   
Histologically or cytologically confirmed advanced solid tumor with no available 
standard treatment options in the opinion of the investigator.   
Eastern Cooperative Oncology Group (ECOG) SHUIRUPDQFHVWDWXV 2.   
(VWLPDWHGOLIHH[SHFWDQF\RI 3 months.   
Able to swallow the study drug, have no known intolerance to the study drug or 
excipients, and comply with study requirements.   
Female patients of childbearing potential (defined in Section 8.2.3) must have a negative 
pregnancy test at screening and must agree to use a highly effective birth control method 
(defined in Section 8.2.3) from the time of the first dose of study drug through 45 days 
after last dose of study drug.   
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.   
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.   
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.   
4.2
Exclusion Criteria 
Each patient eligible to participate in this study must NOT meet any of the following 
exclusion criteria: 
Use of antineoplastic therapies within 21 days before day -1.   
Use of any other investigational agent within 21 days before day -1.   
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.   
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).   


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Major surgery within 14 days before day -1.   
Diagnosis of myelodysplastic syndrome (MDS) or a hematologic malignancy.   
Clinically significant cardiovascular disease, including any of the following:   
x 
Myocardial infarction or symptomatic cardiac ischemia within 6 months before 
day -1 
x 
Heart failure, New York Heart Association class II to IV 
x 
History of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, 
ventricular fibrillation, torsade de pointes) 
x 
History of Mobitz II second degree or third degree heart block 
x 
Atrial arrhythmia (ie, chronic atrial fibrillation or paroxysmal supraventricular 
tachycardia) 
x 
Hypotension as indicated by systolic blood pressure < 100 mm Hg at screening or at 
day -1; a second measurement may be taken after hydration with oral fluids if the first 
measurement was < 90 mm Hg 
x 
Bradycardia as indicated by a heart rate of < 50 beats per minute or tachycardia as 
indicated by a heart rate of > 100 beats per minute on the screening ECG 
x 
Poorly controlled hypertension as indicated by systolic blood pressure > 170 mm Hg 
or diastolic blood pressure > 105 mm Hg at screening 
x 
6FUHHQLQJ47F) 450 msec 
x 
Ventricular pacing (implanted pacemaker or implantable cardioverter-defibrillator 
[ICD]) 
x 
QRS duration > 119 msec 
x 
PR interval > 220 msec 
Significant organ dysfunction as defined by any of the following laboratory abnormalities 
at screening:   
x 
Renal:  estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 by the 
MDRD equation (Modification of Diet in Renal Disease [available via 
www.mdrd.com]) 
x 
Hepatic:   
–
Total serum bilirubin > 1.5 times ULN (> 3 × ULN for patients with documented 
Gilbert syndrome or for whom indirect bilirubin concentrations suggest an 
extrahepatic source of elevation) 
–
$VSDUWDWHDPLQRWUDQVIHUDVH$67RUDODQLQHDPLQRWUDQVIHUDVH$/7 2.5 times 
ULN (if liver function abnormalities are due to hepatic metastasis, then AST and 
ALT > 5 × ULN) 
x 
Bone marrow reserve:  absolute neutrophil count < 1500/μL, platelets < 100,000/μL, 
or hemoglobin < 9 JG/EORRGVDPSOHVFROOHFWHGDIWHU 14 days without growth 
factor support or transfusion) 
Gastrointestinal disorder affecting absorption.   


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Current or anticipated use of a strong P-gp inhibitor (eg, dronedarone, quinidine, 
ranolazine, verapamil, itraconazole, ketoconazole), strong P-gp inducer (eg, rifampin, 
tipranavir, ritonavir), or strong inhibitor of BCRP (eg, elacridar [GF120918]).   
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.   
5
ENROLLMENT AND STUDY PROCEDURES 
Study enrollment and procedures are summarized in the following subsections.  The study 
periods will include screening, treatment (baseline on day -1 and 22 days of treatment), and 
safety follow-up.  The timing of all study procedures is provided in the schedules of activities 
(Appendix 1, Appendix 2).  Signed informed consent must be obtained before performing 
any study-specific procedures.  The study manual contains the information needed for 
registering patient status (eg, assigning screening and enrollment numbers, indicating screen 
failure, and end of treatment).   
5.1 
Screening Period 
The screening period will be from day -29 through day -2.  For the purposes of this study, 
there will be no day 0.   
5.1.1 
Informed Consent 
Study site personnel must explain to potential study participants all aspects of the study, 
including all scheduled visits and activities.  Study site personnel must obtain signed 
informed consent before any study-specific procedures are conducted unless the procedures 
are part of routine standard of care, and must document the informed consent process in the 
patient’s source documents.   
The informed consent form may be signed before the 28-day screening period.   
5.1.2 
Screening Identification Numbers 
After obtaining signed informed consent, study site personnel will assign a screening 
identification (ID) number for each potential study participant per the study manual.   
For patients who provide informed consent and subsequently do not meet eligibility criteria 
or withdraw consent, study site personnel will document the screen failure or consent 
withdrawal in the patient’s source documents.  The documentation will include demographics 
and medical history, the reason for screen failure, the eligibility criteria reviewed, and 
procedures performed.   


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5.1.3 
Screening Procedures 
Screening procedures are listed in the schedule of activities in Appendix 1.  All procedures 
must be completed within 28 days before day -1 except as noted.   
The investigator will assess the eligibility of each patient.  All screening procedure results 
and relevant medical history must be available before eligibility can be determined.  All 
inclusion criteria must be met and none of the exclusion criteria may apply.  No eligibility 
waivers will be granted.   
After a patient is screened and the investigator determines the patient is eligible for 
enrollment, study site personnel will request that the sponsor or designee approve the 
enrollment.   
5.2 
Treatment Period 
5.2.1 
Treatment Period Visit Windows 
All treatment period visits have a visit window of ±3 days (ie, 3 days before or after the 
given day), except for days -1, 1, and 2.   
5.2.2 
Treatment Period Procedures 
5.2.2.1 
Enrollment 
Study site personnel should receive enrollment approval from the sponsor or designee before 
proceeding with enrollment.  An enrollment ID number will be assigned per the study 
manual.  This number will be used to identify the patient for the remainder of the study.  
Patients must initiate study treatment within 3 business days after enrollment approval.   
5.2.2.2 
Treatment Period Study Visit Procedures 
Day -1 is the day of baseline, and day 1 is the day of the first dose of study drug.   
Specified study procedures will be performed at each clinic visit according to the schedule of 
activities (Appendix 2).  The ECG, blood pressure, and PK collection schedule is as follows 
(Appendix 3): 
• 
Continuous ECG recordings are obtained by attaching the Holter monitor at the start 
of the collection time point on days -1, 1, 2, and 22.  Blood pressure (after supine for 
5 minutes) will be obtained 15 to 20 minutes before each PK collection time point.  
After blood pressure is obtained, the patient should remain supine for 10 to 
15 minutes (for continuous ECG recording) before blood samples for PK are 
collected.   
• 
On day -1 (baseline), ECG recording will start at time 0 (corresponding to the dosing 
time on day 1) and continue for 6 hours.   


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• 
Patients will fast for at least 6 hours before and 2 hours after the day 1 dose.   
• 
On day 1 (within 72 hours of time 0 on day -1, corresponding to the clock time of the 
first baseline ECG measurement), ECG recording will start at least 45 minutes before 
the first dose of study drug at time 0, and continue for 6 hours postdose.  Blood 
samples for PK will be collected immediately before the first dose of study drug and 
at 1, 2, 4, and 6 hours postdose.  Patients may resume eating after the 2-hour postdose 
PK sample is collected.   
• 
On day 2, at 24 hours after the first dose of study drug, ECG recording will start at 
least 30 minutes before time 0 and continue until the day 2 dose.  The day 2 dose 
should be taken at approximately the same clock time (within 1 hour of time 0) as the 
day 1 dose.  Blood samples for PK will be collected before the dose.   
• 
Patients will fast for at least 6 hours before and 2 hours after the day 22 dose.   
• 
On day 22, ECG recording will start at least 45 minutes before administration of the 
day 22 dose at time 0, and continue for 6 hours postdose.  The day 22 dose should be 
taken at approximately the same clock time (within 1 hour of time 0) as the day 1 
dose.  Patients may resume eating after the 2-hour postdose PK sample is collected.  
Blood samples for PK will be collected immediately before the dose of talazoparib 
and at 1, 2, 4, and 6 hours postdose.   
5.2.3 
Unscheduled Visit Procedures 
Unscheduled visits may be performed anytime to assess or follow up adverse events or at the 
request of the patient or investigator.  The date and reason for the unscheduled visit must be 
recorded in the source documentation.   
A review of adverse events and changes to concomitant medications or treatments (including 
herbal therapies) occurring since the previous visit should be performed at unscheduled 
visits.   
Unscheduled visit procedures are listed in Appendix 2.  Other study procedures may be 
performed as clinically appropriate.   
5.3 
Permanent Treatment Discontinuation 
Permanent treatment discontinuation is defined as cessation of study drug treatment 
administration.  After permanent discontinuation, safety follow-up will be per Section 5.4, 
unless the patient withdraws consent for further follow-up.   
Temporary treatment interruption (eg, due to an adverse event) is not considered permanent 
discontinuation.   
The primary reasons for which patients permanently discontinue study treatment are listed in 
Table 1.   


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Table 1: Primary Reasons for Permanent Treatment Discontinuation 
Reason 
Comment 
Adverse event or intercurrent illness 
Any intolerable adverse event that cannot be ameliorated by 
the use of adequate medical intervention or that in the opinion 
of the investigator or sponsor would lead to undue risk if 
study treatment were continued (eg, severe drug-induced liver 
injury [Section 8.2.1.1.1] or MDS/AML [Table 3]).  Refer to 
Section 8.3.1.  May or may not be related to disease 
progression.   
Disease progression 
Study drug treatment may be discontinued for disease 
progression based on investigator assessment.   
Administration of prohibited 
concomitant therapy 
Refer to Section 7.2.   
Patient decision 
Patients may permanently discontinue treatment anytime for 
any reason.   
Investigator decision 
Protocol treatment may be discontinued if the investigator 
considers it is in the patient’s best interest.  This category 
should be selected if adverse event, disease progression, or 
administration of prohibited concomitant therapy do not apply 
and the patient preferred to continue treatment.   
Major noncompliance with protocol 
The medical monitor or investigator may request permanent 
treatment discontinuation in the event of a major protocol 
deviation, lack of cooperation, or noncompliance.   
Loss to follow-up 
Refer to Section 5.5.   
Sponsor discontinuation of study 
The sponsor reserves the right to terminate the study anytime 
for any reason as described in Section 13.6.  The sponsor will 
terminate this study following completion of the study 
objectives, or earlier if deemed necessary.   
AML, acute myeloid leukemia; MDS, myelodysplastic syndrome.   
 
5.4 
Safety Follow-Up 
Safety follow-up will occur approximately 30 days after the last dose of study drug or before 
initiation of a new antineoplastic therapy, whichever occurs first.  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, and in this case, 
the safety follow-up will be omitted and an ECG will be obtained at the time of enrollment in 
the open-label extension study.   
In the event that a new antineoplastic therapy is initiated before safety follow-up occurs 
(eg, a physician not associated with protocol MDV3800-14 initiates the treatment, and study 
site personnel are not aware of the treatment until afterward), safety follow-up should be 
scheduled as soon as possible.   
Safety follow-up procedures are listed in Appendix 2.   


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If treatment is discontinued due to an adverse event or serious adverse event, the event(s) 
must be followed up as described in Section 8.3.9.   
For patients who refuse to come to the clinic for safety follow-up, telephone contact must be 
attempted and documented to review for adverse events through approximately 30 days after 
the last study drug treatment, before initiation of a new antineoplastic therapy, or enrollment 
in the open-label extension study, whichever occurs first.  If the patient does not respond to 
telephone calls, the procedures for loss to follow-up in Section 5.5 should be followed.   
5.5 
Loss to Follow-Up 
Every reasonable effort must be made to contact any patient apparently lost to follow-up 
during the course of the study to complete study-related assessments and record outstanding 
data.  Following unsuccessful telephone contact, the following should occur:   
• 
An effort to contact the patient by mail using a method that provides proof of receipt 
should be attempted.   
• 
Alternate contacts are permissible if the patient is not reachable (eg, primary care 
providers, referring physician, relatives).  
• 
Such efforts should be documented in the patient’s source documents.   
If all efforts fail to establish contact, the patient will be considered lost to follow-up.   
Patients who withdraw consent will be considered lost to follow-up for analysis purposes.   
6 INVESTIGATIONAL PRODUCT INFORMATION 
6.1 
General Information 
The study drug is talazoparib.  The sponsor will provide talazoparib capsules.   
6.2 
Talazoparib Product Characteristics 
Talazoparib is provided as the 4-methylbenzenesulfonate (tosylate) salt and has the chemical 
name (8S,9R) 5-fluoro-8-(4-fluorophenyl)-2,7,8,9-tetrahydro-9-(1-methyl-1H-1,2,4-triazol-5-
yl)-3H-pyrido[4,3,2-de]phthalazin-3-one.  The drug product is a capsule containing 
talazoparib tosylate and silicified microcrystalline cellulose.  The capsules for each dose 
strength will be provided in dose-specific colors.  Additional details will be provided in the 
pharmacy binder.   
6.2.1 
Packaging of Talazoparib 
Talazoparib study drug is packaged in induction sealed, high-density polyethylene bottles 
with child-resistant caps.   


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The label will vary depending on individual country requirements.  At minimum, each label 
typically provides the study protocol number, contents, directions for use and storage, 
clinical trial statement, sponsor name, batch/lot number, and product retest or expiration date.   
6.2.2 
Storage of Talazoparib 
The drug product should be stored safely and properly in accordance with the study drug 
label.   
6.2.3 
Directions for Administration of Talazoparib 
The daily dose of talazoparib is 1 mg given orally.   
Talazoparib will be administered at the study site on days 1, 2, and 22.  Patients will fast for 
at least 6 hours before and 2 hours after the dose on days 1 and 22.  Patients may resume 
eating after the 2-hour postdose PK sample is collected.  On other days, talazoparib may be 
taken with or without food.  The days 2 and 22 doses should be taken at approximately the 
same clock time (within 1 hour of time 0) as the day 1 dose.  On days 3 to 21, patients should 
self-administer talazoparib orally once daily at approximately the same time each morning.  
The capsules should be swallowed whole with a glass of water without chewing, dissolving, 
or opening them.   
Patients should not make up missed or vomited doses; dosing should resume on the next 
calendar day unless otherwise instructed.   
Dose modifications due to adverse events are described in Section 8.2.1.   
Talazoparib is considered a cytotoxic and clastogenic agent; precautions regarding 
appropriate secure storage and handling must be used by healthcare professionals, including 
personal protective clothing, disposable gloves, and equipment (Goodin et al, 2011).  Patients 
should be advised that oral anticancer agents are toxic substances and that (other than the 
patient) caregivers should always use gloves when handling the capsules.   
6.3 
Treatment Compliance 
Accountability for the study drug capsules will be performed to document compliance with 
the dosing regimen.  Patients will be asked to bring all used and unused study drug bottles to 
study visits.  Study site personnel must make reasonable efforts to obtain used and unused 
study drug bottles from patients who do not routinely return them at study site visits.  
Unreturned capsules will be considered to have been taken.   
7 PRIOR AND CONCOMITANT THERAPY 
Prior and concomitant medications include all vitamins, herbal remedies, and 
over-the-counter and prescription medications.   


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7.1 
Prior Medications 
All prior cancer treatments, other medications taken within 30 days before day -1, and any 
medications prescribed for chronic or intermittent use during the study, or dose adjustments 
of these medications, must be recorded on the case report form and in the patient’s source 
documents.   
7.2 
Concomitant Therapy 
Concomitant therapy (noninvestigational products) includes any concomitant medications 
(Section 7), blood transfusions, or radiotherapy used between day -1 and the end of 
treatment.   
Patients will be instructed to consult with the investigator before taking any additional 
medications (including over-the-counter medications).  Supportive medications may be 
provided prophylactically or therapeutically per investigator discretion, with the exception 
that granulocyte-colony stimulating factor (G-CSF) is only allowed in the rescue setting.  
Palliative radiation is allowed but the combination of radiation therapy and talazoparib has 
not been studied.   
Concomitant therapies will be assessed at all clinic visits and must be recorded on the 
appropriate case report form.  If the use of any medication during the study is due to 
an adverse event, the adverse event must be recorded on the adverse event case report form 
and in the patient’s source documents.   
Prohibited medications are described in Table 2.  Deviation from these guidelines should 
occur only if absolutely necessary for the well-being of the patient, and the medical monitor 
is to be notified to determine whether continued treatment with study drug is permitted.   
Study drug must be permanently discontinued upon initiation of any other antineoplastic 
therapy.  Patients who discontinue treatment due to initiation of such therapy will complete 
safety follow-up per Section 5.4.   
Table 2: Prohibited Concomitant Therapies 
Medication or Treatment 
Comment on Use 
Any antineoplastic therapy (including 
biologic, radionuclide, or cytotoxic 
chemotherapy 
Within 21 days before day -1 through safety follow-up 
for commercially available or investigational agents.   
Other investigational agent (eg, biologic, 
vaccine, or other agents not approved for 
marketing) 
Within 21 days before day -1 through safety follow-up.   
Live bacterial and virus vaccines 
Anytime between day -1 and safety follow-up.   
 


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7.3 
Potential Interactions Between Talazoparib and Concomitant Medications 
Guidelines for concomitant use of talazoparib with inhibitors or inducers of P-gp or 
inhibitors of BCRP are as follows:  
• 
Use of strong P-gp inhibitors (eg, dronedarone, quinidine, ranolazine, verapamil, 
itraconazole, ketoconazole), P-gp inducers (eg, rifampin, tipranavir, ritonavir), or 
BCRP inhibitors (eg, elacridar [GF120918]) should be avoided.   
• 
Caution should be used for coadministration of other P-gp inhibitors (eg, amiodarone, 
azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, 
diltiazem, erythromycin, felodipine, lopinavir, quercetin), P-gp inducers 
(eg, avasimibe, carbamazepine, phenytoin, St John’s wort), or BCRP inhibitors 
(eg, cyclosporine, eltrombopag, gefitinib).   
• 
Refer to the following website for a complete list:  
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Dr
ugInteractionsLabeling/ucm093664.htm#inhibitors 
8 SAFETY CONSIDERATIONS 
Study assessments of safety include adverse events, physical examinations, vital signs, 
ECGs, and clinical laboratory tests.   
8.1 
Safety Monitoring 
The sponsor will periodically monitor safety data during the clinical study in addition to 
reviewing individual safety case reports, by examining the incidence and severity of adverse 
events and serious adverse events; changes in vital signs, ECG, and laboratory results; and 
other data (such as aggregate analysis of data from other talazoparib studies).  Any relevant 
safety concerns will be communicated to the investigators and regulatory agencies, as 
appropriate.   
8.2 
Special Safety Considerations 
8.2.1 
Dose Modification Due to Adverse Events 
Talazoparib dose modifications due to adverse events are described in Table 3.   


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Table 3: Dose Modification of Study Drug Due to Adverse Events 
Toxicity 
Management of Adverse Events 
Grade 1 or 2 
No requirement for dose interruption or dose reduction.   
Selected hematologic 
grade 3 or 4 events 
 
Anemia  
(hemoglobin 
< 8.0 g/dL) 
Hold talazoparib and monitor weekly until hemoglobin returns to baseline 
(day 1) grade or better.  Implement supportive care per local guidelines.   
• Talazoparib may be reduced by 1 dose level per Table 4.   
If anemia persists for > 4 weeks without recovery to baseline grade, refer to 
a hematologist for evaluation, including assessment for possible MDS/AML.   
Neutropenia  
(ANC < 1000/µL) 
Hold talazoparib and monitor weekly until ANC ≥ 1500/µL.  Implement 
supportive care per local guidelines.  Resume talazoparib based on the 
following recovery times: 
• ≤ 1 week:  No change.   
• > 1 week:  Reduce talazoparib by 1 dose level per Table 4.   
If neutropenia persists for > 4 weeks without recovery to ≥ 1500/µL, refer to 
a hematologist for evaluation, including assessment for possible MDS/AML.   
Thrombocytopenia 
(platelets < 50,000/µL) 
Hold talazoparib until platelets ≥ 75,000/µL.  Implement supportive care per 
local guidelines.  Resume talazoparib based on the following recovery times: 
• ≤ 1 week:  No change. 
• > 1 week:  Reduce talazoparib by 1 dose level per Table 4.   
If thrombocytopenia persists for > 4 weeks without recovery to ≥ 75,000/µL, 
refer to a hematologist for evaluation, including assessment for possible 
MDS/AML.   
Nonhematologic 
laboratory grade 3 or 4 
events, except abnormal 
liver tests 
Hold talazoparib as follows: 
 For clinically significant grade 3 laboratory abnormalities, talazoparib 
may be held.  Resume talazoparib at the same dose or reduce by 1 dose 
level per Table 4 when the laboratory abnormality resolves to grade ≤ 2 
(baseline grade for creatinine increases).   
 For clinically significant grade 4 laboratory abnormalities, hold 
talazoparib.  Resume talazoparib when the laboratory abnormality 
resolves to grade ≤ 2 (baseline grade for creatinine increases) at a 1 dose 
level reduction per Table 4.  
Implement supportive care per local guidelines.   
Contact medical monitor to discuss potential dose modification.   
Talazoparib should be permanently discontinued for unresolved grade 3 
toxicity lasting longer than 2 weeks or for grade 4 toxicity lasting longer 
than 1 week.   
Talazoparib must be discontinued if a grade 4 adverse event recurs after 
study drug treatment resumes.   


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Toxicity 
Management of Adverse Events 
Nonlaboratory grade 3 
or 4 events 
Hold talazoparib as follows: 
 For clinically significant grade 3 adverse events, hold talazoparib until 
the adverse event resolves to grade ≤ 1 or baseline.  Resume talazoparib 
at the same dose or reduce by 1 dose level per Table 4.   
 For clinically significant grade 4 adverse events, hold talazoparib until 
the adverse event resolves to grade ≤ 1 or baseline.  Resume talazoparib 
at a 1 dose level reduction per Table 4.   
Implement supportive care per local guidelines.   
Contact medical monitor to discuss potential dose modification.   
Talazoparib must be permanently discontinued for unresolved grade 3 
toxicity lasting longer than 2 weeks or for grade 4 toxicity lasting longer 
than 1 week.   
Talazoparib must be discontinued if a grade 4 adverse event recurs after 
study drug treatment resumes.   
Grade 3 or 4 abnormal 
liver tests 
Hold talazoparib for liver test abnormalities as specified in Table 5.  
Guidelines for follow-up for possible drug-induced liver injury and for 
resuming talazoparib after the liver test abnormalities resolve to baseline 
grade are provided in Section 8.2.1.1.   
The criteria for permanent discontinuation of talazoparib are provided in 
Section 8.2.1.1.1.  In addition, talazoparib must be discontinued for 
recurrence of signs and symptoms of hepatitis and/or liver test abnormalities 
meeting the withholding criteria in Table 5 following rechallenge.   
AML, acute myeloid leukemia; ANC, absolute neutrophil count; MDS, myelodysplastic syndrome.   
 
Table 4: Talazoparib Dose Reductions for Toxicity 
Talazoparib Dose Level 
Talazoparib Dose (mg/day) 
Initial dose 
1.0 
First dose reduction 
0.75 
Second dose reduction 
0.50 
Third dose reduction 
0.25 
 
Dose re-escalation:  No dose re-escalation is allowed for this study.   
8.2.1.1 
Assessment of Abnormal Liver Tests 
Patients who develop abnormal liver tests (AST, ALT, total bilirubin), abnormal international 
normalized ratio (INR) values, or signs or symptoms of hepatitis during the study treatment 
period may meet the criteria for temporarily withholding or permanently discontinuing study 
drug treatment as specified in United States Food and Drug Administration (US FDA) 
Guidance for Industry Drug-Induced Liver Injury:  Premarketing Clinical Evaluation (2009).  
Patients who meet criteria for permanent discontinuation or temporary withholding of study 


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drug treatment or who do not meet the criteria but who have abnormal liver tests are to be 
followed up according to the recommendations in this section.   
Study drug should be withheld for any liver test abnormality listed in Table 5.   
Table 5: Criteria for Temporary Withholding of Study Drug in Association With 
Liver Test Abnormalities 
Baseline AST or ALT Value 
Elevation 
≤ 3 × ULN 
> 5 × ULN (ALT or AST ≥ 3 × ULN with the presence of signs 
and symptoms consistent with acute hepatitis and/or eosinophilia 
[≥ 500 eosinophils/µL]) 
> 3 × ULN 
> 8 × ULN  
Baseline Total Bilirubin Value 
Elevation 
≤ 1.5 × ULN 
> 3 × ULN (> 5 × ULN in patients with a baseline total bilirubin 
value of > 1.5 × ULN and ≤ 3 × ULN [patients with Gilbert 
syndrome or for whom indirect bilirubin concentrations suggest 
an extrahepatic source of elevation]) 
For rechallenge, dose modification may be required per Table 4.   
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.   
 
Study drug should be withheld pending investigation of alternative causes of liver injury 
(Table 6).  When withholding study drug, follow-up should continue for possible 
drug-induced liver injury until the liver test abnormalities resolve to baseline grade.   
Rechallenge may be considered at a 1 dose level reduction per Table 4 if an alternative cause 
for the abnormal liver tests (ALT, AST, total bilirubin) is discovered and the laboratory 
abnormalities resolve to normal or baseline values.  The investigator and sponsor should 
discuss and agree with any decision to rechallenge.   
Following rechallenge, patients should be closely monitored for signs and symptoms of 
hepatitis and/or abnormal liver test results.  If signs or symptoms consistent with hepatitis 
recur or the withholding criteria in Table 5 are met after rechallenge, study drug treatment 
should be permanently discontinued.   
Rechallenge should not occur when the etiology of the liver test abnormalities is considered 
drug induced.   


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Table 6: Investigations of Alternative Causes for Abnormal Liver Tests 
Recommended tests 
Complete blood count with differential to assess for eosinophilia 
Serum total immunoglobulin G (IgG), antinuclear antibody (ANA), antismooth muscle antibody, 
liver kidney microsomal antibody 1 (LKM1), and liver cytosol type 1 antibodies (L-C-1) to assess 
for autoimmune hepatitis 
Serum acetaminophen (paracetamol) concentration 
Obtain a more detailed history 
Prior and concurrent diseases or illness 
Exposure to environmental and/or industrial chemical agents  
Symptoms (if applicable) including right upper quadrant pain, hypersensitivity-type reactions, 
fatigue, nausea, vomiting, and fever 
Prior and concurrent use of alcohol, recreational drugs, and special diets 
Concomitant use of medications (including nonprescription medicines and herbal and dietary 
supplements), plants, and mushrooms 
Obtain viral serologies for hepatitis A, B, C, and E (D if positive for hepatitis B), cytomegalovirus, 
Epstein-Barr virus, herpes simplex virus 
Recommended tests as clinically indicated 
Echocardiogram (ECHO) 
Serum and urine copper and serum ceruloplasmin  
Iron studies (serum iron and ferritin) and transferrin saturation 
Serology for celiac disease  
Serum alpha-1 antitrypsin  
Creatine phosphokinase (CPK), haptoglobin, lactate dehydrogenase (LDH), and peripheral blood 
smear 
Appropriate liver imaging 
Hepatology consult (liver biopsy may be considered in consultation with a hepatologist) 
8.2.1.1.1
Criteria for Permanent Discontinuation of Study Drug in Association With 
Liver Test Abnormalities 
Study drug should be discontinued permanently if all of the following 4 criteria are met 
(ie, potential severe drug-induced liver injury/Hy’s law case):  
$67RU$/7LQFUHDVHVWR 3 times ULN (> 5 × ULN if baseline ALT/AST is 
> 3 × ULN) 
Total bilirubin increases to > 2 times ULN or INR > 1.5 
Alkaline phosphatase value does not reach 2 times ULN (note: in the presence of elevated 
alkaline phosphatase associated with bone metastases, gamma glutamyl transferase 
[GGT] should be tested and the results should be within the reference range) 


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No alternative cause explains the combination of the above laboratory abnormalities; 
important alternative causes include, but are not limited to the following: 
x 
Hepatobiliary tract disease 
x 
Viral hepatitis (eg, hepatitis A/B/C/D/E, Epstein-Barr virus, cytomegalovirus, herpes 
simplex virus, varicella, toxoplasmosis, and parvovirus) 
x 
Congestive heart failure, hypotension, or any cause of hypoxia to the liver causing 
ischemia 
x 
Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and dietary 
supplements, plants, and mushrooms 
x 
Alcoholic hepatitis 
x 
Nonalcoholic steatohepatitis (NASH) 
x 
Autoimmune hepatitis  
x 
Wilson disease and hemochromatosis 
x 
Alpha-1 antitrypsin deficiency  
If an alternative cause for hepatotoxicity is identified or less stringent conditions developed 
than those noted above, then it should be determined (based on the patient population and/or 
severity of the hepatotoxicity or event) whether study drug should be withheld or 
permanently discontinued as appropriate for the safety of the patient.  When study drug is 
temporarily withheld or permanently discontinued due to a potential drug-induced liver 
injury, a period of close observation is to commence until the liver test abnormalities return 
to baseline or normal values.  The evaluations listed in Table 7 should be performed.   
Table 7: Monitoring of Liver Tests for Potential Drug-Induced Liver Injury 
Results 
Frequency for Repeating Liver (AST, ALT, 
Bilirubin [Total and Direct]) and INR Tests  
After the initial liver test abnormality  
Within 24 hours  
,I$67RU$/7î8/1! 5 × ULN if 
baseline ALT/AST is > 3 × ULN), and total 
bilirubin > 2 × ULN or INR > 1.5 
Every 24 hours until laboratory abnormalities 
improve 
,I$/7RU$67î8/1! 5 × ULN if 
baseline ALT/AST is > 3 × ULN) and total 
bilirubin or INR are normal  
Every 48 to 72 hours until laboratory abnormalities 
improve 
If the liver test abnormalities improve AND the 
patient is asymptomatic 
Frequency may decrease 
ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio; 
ULN, upper limit of normal.   
As drug-induced liver injury is a diagnosis of exclusion, it is important to initiate 
investigation of alternative causes for abnormal liver tests, which may include consultation 
with a hepatologist.  The medical monitor should be contacted for questions regarding 
adequate follow-up tests.   


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8.2.2
Overdose Management 
The medical monitor must be contacted in the event of a study drug overdose.  An overdose 
is defined as any dose greater than the protocol-specified dose of talazoparib.  In the event of 
an overdose, treatment with study drug should be stopped and general supportive measures 
initiated, taking into consideration the mean half-life is 50 hours.  No antidote to overdose is 
known.   
All overdose events are to be reported within 24 hours of awareness by the study site 
according to Section 8.3.6 whether or not the overdose is associated with an adverse event.   
8.2.3 
Reproductive Considerations 
Female Patients 
Female patients of childbearing potential must have a negative pregnancy test at screening 
(serum tested centrally) and safety follow-up (urine or serum tested locally or using a 
centrally provided kit), and must avoid pregnancy during the study.  Urine pregnancy tests 
must have a limit of detection of 25 IU/L (or equivalent units) for human chorionic 
gonadotropin.  If a pregnancy test is positive, study drug treatment will be discontinued.   
Female patients of childbearing potential must use a highly effective form of birth control 
from the first dose of study drug through 45 days after the last dose of study drug, defined as 
follows:   
x 
Established use of an oral, intravaginal, or transdermal combined (estrogen and 
progestogen containing) hormonal contraception associated with inhibition of 
ovulation 
x 
Established use of an oral, injectable, or implantable progestogen-only hormonal 
contraception associated with inhibition of ovulation 
x 
Placement of an intrauterine device or intrauterine hormone-releasing system 
x 
%LODWHUDOWXEDOOLJDWLRQIRU 6 months before day -1 
x 
3DUWQHUYDVHFWRPL]HGIRU 6 months before day -1 
x 
Sexual abstinence when in relation to the preferred and usual lifestyle of the patient 
Female patients who meet 1 of the following criteria are considered not of childbearing 
potential: 
Surgically sterile (bilateral salpingectomy, bilateral oophorectomy, or hysterectomy)  
OR 
Postmenopausal, defined as follows:  
x 
 55 \HDUVRIDJHZLWKQRVSRQWDQHRXVPHQVHVIRU 12 months before day -1 
x 
< 55 \HDUVRIDJHZLWKQRVSRQWDQHRXVPHQVHVIRU 12 months before day -1 and 
with a postmenopausal follicle-stimulating hormone (FSH) concentration > 30 IU/L 


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Male Patients 
Male patients must use a condom when having sex with a pregnant woman or with a woman 
of childbearing potential from the first dose of study drug through 105 days after the last dose 
of study drug.  Contraception should be considered for a nonpregnant female partner of 
childbearing potential.   
Details regarding the reporting procedures to follow in the event of pregnancy are provided 
in Section 8.3.10.  Instructions regarding sperm or egg donation and breastfeeding are 
provided in Section 4.1.   
8.3 
Adverse Event Definitions and Reporting 
8.3.1 
Adverse Event Definitions 
Definitions are provided in this section for adverse events, events of special interest, serious 
adverse events, treatment-emergent adverse events, suspected unexpected serious adverse 
reactions (SUSARs), and unexpected adverse events.   
Adverse events:  An adverse event is 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.   
Examples of adverse events include the following: 
• 
A worsening, excluding minor fluctuations, in the nature, severity, frequency, or 
duration of a pre-existing condition 
• 
Development of an intercurrent illness during the study 
• 
Development of symptoms that may or may not be related to the use of a concomitant 
medication or investigational product 
• 
Injury or accidents:  If a medical condition is known to have caused the injury or 
accident, the medical condition and the accident should be reported as 2 separate 
medical events (eg, for a fall secondary to dizziness, both “dizziness” and “fall” 
should be recorded separately) 
• 
An investigational abnormality (eg, laboratory parameter, vital sign, ECG) only if the 
abnormality is considered clinically significant by the investigator based on at least 
one of the following criteria: 
– Induces clinical signs or symptoms 
– Requires active intervention 
– Requires interruption or discontinuation of study drug 
An adverse event does not include the following: 
• 
Medical or surgical procedures (eg, surgery, endoscopy, tooth extraction, 
transfusion); the condition that leads to the procedure is an adverse event 


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• 
Pre-existing diseases or conditions present or detected before the start of study drug 
administration that do not worsen 
• 
Situations where an untoward medical event has not occurred (eg, planned 
hospitalization for an elective procedure) 
Serious adverse events:  Any adverse event that meets any of the criteria in Table 8 as 
determined by the investigator or sponsor.   
Table 8: Criteria for Serious Adverse Events 
Criterion 
Comment 
Results in death 
Death is an outcome, not an adverse event.  The 
primary adverse event resulting in the death 
should be identified.   
Is life threatening (immediate risk of death from 
the adverse event as it occurred) 
Does not include an event that hypothetically 
might have caused death if it were more severe.   
Results in or prolongs an existing inpatient 
hospitalization 
For hospitalizations for surgical or diagnostic 
procedures, the illness leading to the surgical or 
diagnostic procedure will be identified as the 
serious adverse event (not the procedure).   
Results in persistent or significant incapacity or 
substantial disruption of the ability to conduct 
normal life functions 
Permanent or substantial disruption of a person’s 
ability to conduct normal life functions.   
Results in a congenital anomaly/birth defect 
 
Important medical events which jeopardize the 
subject and may require medical or surgical 
intervention to prevent one of the outcomes listed 
above 
Examples include drug-induced bronchospasm 
requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, and 
the development of drug dependency or drug 
abuse.   
Source:  US Code of Federal Regulations:  21 CFR 312.32 [75 FR 59961] 
 
Treatment-emergent adverse events:  Adverse events observed following administration of 
the first dose of study drug.   
Unexpected adverse events:  Adverse events for which the nature or severity is not consistent 
with the reference safety information.   
Suspected unexpected serious adverse reactions (SUSARs):  Adverse events assessed as 
serious, related, and unexpected, which are subject to expedited reporting to regulatory 
authorities and study investigators.   
Adverse events of special interest:  Adverse events of special interest are any adverse events 
(serious or nonserious) identified for ongoing monitoring during the study and require rapid 
communication by the investigator to the sponsor as described in Section 8.3.6.   


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8.3.2 
Adverse Event Reporting 
Safety reporting to regulatory authorities, ethics committees, and investigators will be 
implemented according to global and country specific regulations.   
To elicit adverse event reports from patients, the study site personnel should question the 
patient in a general way without suggesting specific symptoms.   
All patients who experience an adverse event will be evaluated at appropriate time intervals 
until the event resolves or stabilizes.  At the conclusion of the study, the investigator and 
medical monitor will assess unresolved adverse events and determine if additional follow-up 
is warranted as described in Section 8.3.9.   
All adverse events, whether or not related to the study drug, must be fully and completely 
documented on the appropriate form and in the patient’s source documents.  In addition, any 
adverse event resulting in permanent treatment discontinuation must be recorded on the 
appropriate case report form as well as documented in the patient’s source documents.  
Adverse event terms should include a diagnosis, as available, in preference to listing the 
individual signs and symptoms.  If the diagnosis is not known, the investigator should record 
each sign and symptom as an individual adverse event.   
Overdose and pregnancy in the patient or partner will be reported as described in 
Sections 8.2.2 and 8.3.10, respectively.   
8.3.2.1 
Adverse Event Reporting Periods 
Collection and reporting of adverse event information will begin at the time the patient signs 
informed consent for serious adverse events and following the first dose of study drug for 
nonserious adverse events and will continue for all events through safety follow-up 
(approximately 30 days after the last dose of study drug), before initiation of a new 
antineoplastic therapy, or enrollment in the open-label extension study, whichever occurs 
first (Figure 2).  Additional reporting instructions for serious adverse events are provided in 
Section 8.3.6.   


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Figure 2: Adverse Event Reporting Periods 
 
All adverse events from the time of the first dose of study drug must be documented on the 
adverse event case report form and in the patient’s clinical record.  Any event occurring 
during screening and before the first dose must be documented on the medical history case 
report form and in the patient’s clinical record for any patient who subsequently meets 
eligibility criteria and proceeds to enrollment.   
8.3.3 
Assessment of Causal Relationship 
The investigator will assess the relationship of an adverse event to study drug treatment 
according to the criteria in Table 9 and document the relationship in the patient’s clinical 
record.   
Table 9: Criteria for Determining Causal Relationship to Study Drug 
Relationship 
Criteria  
Not Related 
A clinical event, including laboratory test abnormality, with a 
temporal relationship to drug administration that makes a causal 
relationship improbable, and/or in which other drugs, chemicals, 
or underlying disease provide plausible explanations.   
Possible 
A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to administration of the drug, but that could 
also be explained by concurrent disease or other drugs or chemicals.  
Information on drug withdrawal may be lacking or unclear.   
Probable 
A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to administration of the drug, unlikely to be 
attributed to concurrent disease or other drugs or chemicals, and that 
follows a clinically reasonable response on re-administration 
(rechallenge) or withdrawal (dechallenge).   
 
Screening
First 
Dose
Return Clinic 
Visits
30 Days 
After Last 
Dose
Nonserious adverse event reporting
Last 
Dose*
Signed 
informed 
consent 
Serious adverse event reporting
Random-
ization
* Approximately 30 days after last dose of study drug treatment, 
before a new antineoplastic therapy, or enrollment in the open-label 
extension study, whichever occurs first.    
Screening
First 
Dose
Return Clinic 
Visits
Safety 
Follow-Up *
Nonserious adverse event reporting
Last 
Dose
Signed 
informed 
consent 
Serious adverse event reporting
Enrollment 
(day -1)
Permanent
discontinuation


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8.3.4 
Assessment of Severity (Intensity) 
Severity describes the intensity of a specific adverse event (mild, moderate, or severe).  The 
particular event may be of relatively minor medical significance (such as severe headache).  
Severity is not the same as “serious,” which is based on patient/event outcome or action 
criteria.   
Investigators will grade the severity of adverse events according to the CTCAE, version 4.  
For terms not specified within the CTCAE, the criteria in Table 10 should be used to 
determine grade of severity.   
Adverse event severity should be recorded in the appropriate section of the adverse event 
case report form and in the patient’s source documents.   
Table 10: Criteria for Determining the Severity (Intensity) of an Adverse Event for 
Terms Not Specified in CTCAE 
Grade 
Intensity or Severity 
Clinical Description 
1 
Mild 
Asymptomatic or mild symptoms, clinical or diagnostic 
observations only; intervention not indicated 
2 
Moderate 
Minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living 
3 
Severe or medically 
significant 
Not immediately life-threatening; hospitalization or prolongation of 
hospitalization indicated; disabling; limiting self-care activities of 
daily living 
4 
Life-threatening  
Life-threatening consequences; urgent intervention indicated 
5 
Death 
Death related to adverse event 
Source:  Common Terminology Criteria for Adverse Events v4.0 
 
8.3.5 
Adverse Events of Special Interest 
Adverse events of special interest include a diagnosis of MDS or acute myeloid leukemia 
(AML) (consistent with events observed with olaparib) and abnormal liver test results.  Liver 
test abnormalities that require reporting are the following: 
• 
AST or ALT ≥ 3 times ULN (> 5 × ULN if baseline ALT/AST is > 3 × ULN) and 
total bilirubin > 2 times ULN or INR > 1.5 
• 
AST or ALT ≥ 3 times ULN with signs and symptoms consistent with hepatitis 
and/or eosinophilia (≥ 500 eosinophils/µL) 
Adverse events of special interest occurring during the safety reporting period must be 
reported within 24 hours of awareness by the study site and those occurring after the safety 
reporting period must be reported within 1 week of awareness, using a serious adverse event 
report form (contact information provided in Section 8.3.6).   


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Tissue samples and any other supporting data used to enable the diagnosis of MDS or AML 
should be submitted for central review if requested.   
8.3.6 
Serious Adverse Event Reporting 
Study site personnel will collect serious adverse event information from the time the patient 
signs the informed consent form through screen failure or safety follow-up (approximately 
30 days after the last dose of study drug), before initiation of a new antineoplastic therapy, or 
enrollment in the open-label extension study, whichever occurs first.  Serious adverse events 
reported to the investigator after the safety reporting period should be reported to the sponsor 
if the investigator assesses the event as related to the study drug treatment.   
Using a serious adverse event report form (a sponsor-provided form in the study manual), all 
serious adverse events must be reported within 24 hours of the study site personnel’s 
knowledge of the event, regardless of the investigator assessment of the relationship of the 
event to study drug.   
The contact information for submission of serious adverse events, adverse events of special 
interest, and events of overdose or pregnancy is as follows: 
Name: 
ProductLife, Ltd. 
Fax: 
+1-866-488-3347 (US)  
or designated regional toll-free number 
Backup Fax: 
+44 (0) 1223 413689 (United Kingdom) 
Email: 
safety@productlife-group.com 
Phone: 
+44 (0) 1223 402660 
 
The initial report should include, at minimum, the following: 
• 
Study number (MDV3800-14) 
• 
Site name and number 
• 
Investigator name 
• 
Patient ID number, sex, and age 
• 
Details of study drug administration 
• 
The date of the report 
• 
A description of the serious adverse event (event term, seriousness of the event) 
• 
Causal relationship to the study drug 
If the patient died, the report should include the cause of death as the event term (with fatal 
outcome) and whether or not the event leading to death was related to study drug treatment, 
as well as the autopsy findings if available.   


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8.3.7 
Clarification in Reporting of Deaths 
Information relating to any death at any time during the study (eg, date and primary cause) 
should be obtained and recorded on the appropriate case report form.   
Fatal events (regardless of relationship to study drug) should be reported as serious adverse 
events during the treatment-emergent safety reporting period defined in Section 8.3.2.   
Death per se is not an adverse event but is an outcome of an adverse event.  The specific 
cause of death should be reported whenever possible.   
8.3.8 
Clarification in Reporting of Disease Progression as an Adverse Event Term 
Disease progression is expected in this study population and “disease progression” should not 
be reported as an adverse event term.  When clinical disease progression is identified, the 
specific clinical event that identifies the disease progression should be reported as the 
adverse event term for standard adverse event and if applicable, serious adverse event 
reporting.   
8.3.9 
Follow-Up of Serious and Nonserious Adverse Events 
All adverse events reported during the study should be followed up at appropriate intervals 
until resolution, or until the event has stabilized, reached a new baseline, or a new 
antineoplastic therapy is initiated (all follow-up results are to be reported to the sponsor or 
designee).   
Adverse events that remain unresolved at the conclusion of the study may continue to be 
monitored if warranted based on clinical assessment by the investigator and medical monitor.   
Patients should be contacted by phone and written requests as appropriate for adverse event 
follow-up if they do not come to the clinic for safety follow-up as specified in Section 5.4.   
8.3.10 Pregnancy Reporting Procedure 
If a female study participant becomes pregnant between the first dose of study drug and 
45 days after permanent discontinuation of study drug treatment, or if a male study 
participant impregnates a partner between the first dose of study drug and 105 days after 
permanent discontinuation of study drug treatment, the study participant should report the 
pregnancy to the investigator.  The pregnancy is to be reported to the sponsor within 24 hours 
of awareness by the study site (contact information provided in Section 8.3.6), using the 
provided reporting forms.  The expected date of delivery or expected date of the end of the 
pregnancy, last menstruation, estimated conception date, pregnancy result, and neonatal data, 
etc, should be included in this information.   
The investigator will follow the medical status of the mother, as well as the fetus, and will 
report the outcome to the sponsor.   


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8.4 
Clinical Laboratory Tests 
Routine clinical laboratory tests (hematology, serum chemistry) will be performed according 
to the schedules of activities (Appendix 1, Appendix 2).  Samples will be stored until the 
specified analyses are completed and then will be destroyed in accordance with standard 
laboratory practice and applicable local regulations.   
A list of the required routine clinical laboratory tests and other evaluations is provided in 
Table 11.  All samples for laboratory analysis must be collected, prepared, labeled, and 
shipped according to laboratory requirements.   
All clinical laboratory tests will be performed by the central laboratory specified in Form 
FDA 1572 Section 4 unless otherwise specified.  The central laboratory reference ranges will 
be used.  Eligibility at screening will be based on central laboratory assessments.   
A local clinical laboratory may be used to evaluate serum chemistry and hematology within 
3 days before a scheduled visit.  The results of these local laboratory assessments will be 
used for dosing decisions.   
For all patients, a local clinical laboratory may be used to assess samples at unscheduled 
visits or for urgent care to evaluate an adverse event.  Such laboratory data will not be 
entered into the study database and local laboratories will not be included on Form 
FDA 1572.  Central laboratory samples should be obtained whenever possible during 
unscheduled visits.   
Table 11: Central Laboratory Tests 
Hematology 
Chemistry 
Additional Tests 
Hematocrit  
Hemoglobin 
Mean corpuscular volume 
Red blood cell count 
Platelet count 
 
White blood cell count with 
differential 
 Total neutrophils 
 Lymphocytes 
 Monocytes 
 Eosinophils 
 Basophils 
Albumin  
Total protein  
Alkaline phosphatase  
ALT (alanine aminotransferase) 
AST (aspartate aminotransferase) 
Total bilirubin 
Blood urea nitrogen 
Creatinine 
Glucose (nonfasting) 
Bicarbonate 
Calcium  
Chloride  
Magnesium 
Phosphate 
Potassium 
Sodium 
LDH (lactate dehydrogenase) 
Urine or serum pregnancy tests for 
women of childbearing potential 
[1] 
[1] The screening serum pregnancy test will be performed centrally.  Other urine or serum pregnancy tests 
may be performed either locally or using a centrally provided kit.   
 


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8.5 
Physical Examinations, Vital Signs, and ECGs 
The investigator will perform physical examinations according to the schedules of activities 
(Appendix 1, Appendix 2).  Interval medical history will be reviewed as a part of physical 
examinations.   
Physical examinations will include an assessment of systems (eg, general appearance, head, 
eyes, ears, nose, mouth, skin, heart, lungs, lymph nodes, gastrointestinal, genitourinary, 
neurologic, and skeletal) per standard of care at the study site or as clinically indicated by 
symptoms.   
Vital sign measurements will include blood pressure (after supine for 5 minutes), heart rate, 
respiratory rate, and temperature at the visits noted in the schedule of activities.  Blood 
pressure (after supine for 5 minutes) will be measured 15 to 20 minutes before each PK time 
point.  Weight will be measured at the time of the examination.  Height will be measured 
only at screening.   
12-Lead ECGs will be obtained continuously at baseline (day -1) and days 1, 2, and 22, and 
a single ECG will be obtained at screening and safety follow-up.  ECGs will be collected for 
analysis at specified time points; patients must be supine for 10 minutes before these time 
points.  Additional ECGs may be obtained as necessary per standard of care.  For patients 
who enroll and initiate continued talazoparib treatment in the open-label extension study 
within 30 days, an ECG will be obtained at the time of enrollment in the open-label study.   
9 ASSESSMENT OF SAFETY, PHARMACOKINETIC, AND EFFICACY 
ENDPOINTS 
9.1 
Assessment of Safety 
The assessment of safety will include adverse events, physical examinations, vital signs, 
ECGs, and clinical laboratory tests.  The procedures for the investigator assessment of 
adverse events are presented in detail in Section 8.  The procedures for clinical laboratory 
safety tests are presented in Section 8.4, and for physical examinations, vital signs, and ECGs 
in Section 8.5.   
9.2 
Assessment of QTc 
ECG recordings from continuous 12-lead ECG recordings will be obtained using Holter 
monitors on days -1, 1, 2, and 22, and will be submitted for independent central review.  
After reviewing for data quality, triplicate 10-second ECGs will be extracted from a 5-minute 
extraction window at each planned time point and will be analyzed for measurement of RR, 
PR, QRS, and QT intervals and evaluation of ECG morphology.  A cardiologist will verify 
the interval durations and perform the morphology analyses.  Heart rate will be used to assess 
QTc endpoints.   


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9.3 
Assessment of PK 
Blood samples will be collected according to the schedules of activities (Appendix 2).  
Samples will be processed as described in the laboratory manual.  Plasma talazoparib 
concentrations will be measured using a validated method.   
9.4 
ECOG Performance Status 
Assessment of ECOG performance status is required to assess patient functional status for 
study eligibility purposes and will be performed throughout the study according to the 
schedules of activities (Appendix 1, Appendix 2).  Scoring for the assessment is shown in 
Table 12.   
Table 12: ECOG Performance Status 
Score 
Description of Functional Status 
0 
Fully active, able to carry on all predisease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities.  Up and 
about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair 
5 
Dead 
Source:  Oken et al, 1982 
ECOG, Eastern Cooperative Oncology Group.   
 
9.5 
Assessment of Efficacy 
No efficacy assessments are planned in this study.  Disease assessments will be conducted 
according to the standard of care at the study site.   
10 STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION 
10.1 Statistical and Analytical Plans 
The statistical methods and analyses for this study will be described in detail in the statistical 
analysis plan.   
10.2 Analysis Populations 
All safety analyses will be performed using the safety population, defined as all patients who 
receive any amount of talazoparib.   


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The ECG analysis population is defined as all enrolled patients who receive at least 1 dose of 
study drug, and have at least 1 available baseline and 1 on-treatment ECG.  Patients who do 
not complete day 22 or who miss > 5 consecutive doses of study drug will be excluded from 
the analysis of the effects of talazoparib on cardiac repolarization.   
The PK population is defined as all patients who receive at least 1 dose of talazoparib and 
provide at least 1 reportable concentration.  The PK analysis population is defined as all 
patients who have sufficient concentration data to derive at least 1 PK parameter.  Additional 
patients may be excluded from the PK population at the discretion of the pharmacokineticist.   
The PK-PD analysis population is defined as all patients in the ECG analysis population who 
have at least 1 time-matched pair of plasma concentration and ECG measurements obtained 
at the same nominal time point.  Additional details on the PK-PD analysis population are 
provided in the statistical analysis plan.   
10.3 Safety Analyses 
All safety analyses will be performed using the safety population, as defined in Section 10.2.  
Drug exposure will be summarized using descriptive statistics.   
The safety of talazoparib will be evaluated by the analysis of incidence of serious and 
nonserious adverse events, severity of adverse events, incidence of dose modifications and of 
permanent treatment discontinuation due to adverse events, and incidence of new clinically 
significant changes in vital signs, ECGs, and clinical laboratory values.  Treatment-emergent 
safety data will be collected from the first dose of study drug treatment through 30 days after 
the last dose (ie, permanent discontinuation), before initiation of a new antineoplastic 
therapy, or enrollment in the open-label extension study, whichever occurs first.   
Adverse events will be coded to preferred term and system organ class using the Medical 
Dictionary for Regulatory Activities (MedDRA) and classified by severity using the CTCAE 
version 4.  The number and percentage of patients with adverse events will be presented by 
MedDRA system organ class and preferred term, relationship to study treatment, severity, 
seriousness, and outcome (eg, leading to permanent treatment discontinuation).   
Laboratory values will be classified for severity using the CTCAE version 4.  Laboratory 
shift tables of baseline results versus postbaseline results to each subsequent visit will be 
produced as appropriate.   
10.4 ECG Analyses 
All ECG analyses will be conducted using the ECG analysis population.  The primary 
endpoints of the study are to evaluate the effects of talazoparib on the QTcF, and to evaluate 
the relationship between the plasma concentration of talazoparib and the change from 
baseline in QTc, corrected for heart rate based on the QTcF correction formula (∆QTcF).  
The time-matched change from baseline in QTc, corrected for heart rate based on Bazett’s 
correction formula (∆QTcB), will also be evaluated.  Changes from time-matched baseline 
measurements will be calculated and data will be summarized in tabular and graphic formats 


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for each study visit.  Assessments include absolute QTc prolongation with QTc > 450 msec, 
> 480 msec, and > 500 msec and change from baseline in QTc with QTc increase > 30 msec 
and > 60 msec.  The means of each measurement of RR, PR, QRS, and QT intervals will be 
utilized for statistical analyses.   
ECG morphology and changes from baseline for each planned postbaseline time point will be 
summarized for all patients.  The proportion of patients with any postbaseline change in ECG 
morphology and the proportion of patients with each type of abnormality will also be 
summarized.   
10.5 
PK Analyses 
Summary data of plasma talazoparib concentrations will be presented in tabular and graphic 
formats for each time point.  PK parameters such as Tmax, Cmax, and AUC on days 1 and 22 
will be calculated.   
In addition, the PK data from this study will be combined with PK data from other studies to 
define a population PK model, which will be reported separately.   
10.6 
PK-PD Analyses 
The correlation between changes in ECG interval measurements from time-matched baseline 
and the plasma talazoparib concentration will be investigated using a linear mixed-effects 
model.   
This analysis will be conducted using the PK-PD analysis population.   
10.7 
Efficacy Analyses 
No efficacy analysis is planned in this study.   
10.8 
Determination of Sample Size 
A sample size of at least 30 evaluable patients will provide 80% power to reject the null 
hypothesis if the mean change from baseline in QTcF is ≥ 10 msec with a 95% one-sided 
alpha, assuming a standard deviation of 20 msec.  Patients will be enrolled until 30 patients 
complete day 22, miss ≤ 5 consecutive doses of study drug, have technically adequate ECG 
recordings, and have at least 80% of specified PK samples collected representing all 3 days 
of observation (days 1, 2, and 22).   
11 STUDY COMMITTEES AND COMMUNICATIONS 
No formal study committees are planned for this study.   


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12 LABORATORY REQUIREMENTS 
A central laboratory will analyze the clinical laboratory safety samples for this study, unless 
otherwise noted, as described in Section 8.4.  The laboratory manual for this study provides 
details regarding sample collection procedures and laboratory tests.   
13 INVESTIGATOR AND ADMINISTRATIVE REQUIREMENTS 
Before initiating the study, the investigator must provide the following documents to the 
sponsor: 
• 
Fully executed and signed Form FDA 1572 
• 
Fully executed clinical trial agreement 
• 
Current curriculum vitae (also applies to all subinvestigators listed on the 
Form FDA 1572) 
• 
Financial disclosure (also applies to all subinvestigators listed on the 
Form FDA 1572) 
• 
Signed protocol signature page 
• 
Signed acknowledgment of receipt of the current investigator brochure 
• 
Ethics committee (EC) approval letter 
• 
EC-approved informed consent form 
• 
Additional documents as necessary per local requirements 
If an investigator changes during the course of the study, the sponsor and any local regulatory 
authorities, as applicable, must first approve the change of investigator and the new 
investigator must provide the sponsor all of the documents listed above.   
The sponsor personnel or representatives may visit the study site, if necessary, before 
initiation of the study to review information with study site personnel about protocol 
requirements pertaining to the study drug, case report forms, monitoring, serious adverse 
event reporting, and other relevant information.   
13.1 Ethics 
13.1.1 Ethics Committee 
Before initiating the study, the investigator will obtain confirmation from the EC that the 
EC is properly constituted and compliant with all requirements and local regulations.   
The investigator will provide the EC with all appropriate material, such as the protocol, 
current investigator brochure, site-specific informed consent form, and other written 
information provided to the patients.  The study will not be initiated until the investigator 
obtains appropriate EC approval in writing for the protocol and informed consent document, 
and copies are received by the sponsor.   


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EC and health authority approval will be obtained for any substantial protocol amendments 
and informed consent revisions before implementing the changes.  The investigator will 
provide appropriate reports on the progress of the study to the EC, per local requirements, 
and to the sponsor or designee in accordance with applicable local regulations.   
13.1.2 Ethical Conduct of the Study 
This study will be conducted under the guiding principles of the World Medical Association 
Declaration of Helsinki, including current Good Clinical Practice (GCP) according to 
International Conference on Harmonisation (ICH) guidelines.  Specifically, this study is 
based on adequately performed laboratory and animal experimentation; the study will be 
conducted under a protocol reviewed and approved by an EC; the study will be conducted by 
scientifically and medically qualified persons; the anticipated benefits of the study are in 
proportion to the risks; the rights and welfare of the patients will be respected; the physicians 
conducting the study do not find the hazards to outweigh the potential benefits; and each 
patient will provide written informed consent before any protocol-specific tests or 
evaluations are performed.   
13.1.3 Patient Information and Informed Consent 
A properly executed, written informed consent, in compliance with the Declaration of 
Helsinki, ICH GCP, US Code of Federal Regulations (CFR) for Protection of Human 
Subjects (21 CFR 50.25[a,b], CFR 50.27, and CFR Part 56, Subpart A), and local 
regulations, will be obtained from each patient before entering the patient in the trial.  
The investigator or designee will prepare the informed consent form and provide the 
documents to the sponsor or designee for approval before submission to the EC.  The sponsor 
and the EC must approve the documents before the investigator implements them.   
The investigator will provide copies of the signed informed consent form to each patient and 
will maintain the signed original document within the patient’s clinical record per local 
requirements.  The investigator will also fully document the informed consent process in the 
patient’s source documents.   
13.1.4 Maintaining Patient Confidentiality 
All reports and patient samples will be identified only by a screening or enrollment ID 
number and actual initials (if permitted) or mock initials and date of birth (month/year only if 
no date is permitted) in order to maintain patient confidentiality.  Additional patient 
confidentiality issues are addressed in the clinical trial agreement and in the informed 
consent form signed by each study participant.   


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13.2 Data Quality Assurance 
13.2.1 Data Management 
Clinical data management will be performed by the sponsor or designee according to 
procedures described in a comprehensive data management plan.  The data management plan 
will include procedures for processing the data from this study, and will describe the 
responsibilities of the sponsor and designee when clinical data management is provided by an 
external vendor.  In particular, the data management plan will include a list of the standard 
operating procedures that apply to this study.   
Adverse events and medications will be coded using MedDRA and the World Health 
Organization Drug Dictionary (WHO-DD), respectively.  The dictionary versions will be 
named in the data management plan.   
13.2.2 Case Report Forms 
The study will use an electronic data capture system.  All electronic case report forms will be 
designed and provided electronically to the site by the sponsor or designee and electronic 
data capture system vendor.  All case report form books are to be filled out completely, 
reviewed, and signed by the investigator or subinvestigators listed on the Form FDA 1572 or 
other appropriate local health authority documents.   
13.2.3 Study Monitoring 
The sponsor or designee will monitor this study in accordance with current GCP guidelines.  
By signing this protocol, the investigator grants permission to the sponsor or designee and 
appropriate regulatory authorities to conduct onsite monitoring of all appropriate study 
documentation.  To ensure the accuracy of data collected on the case report forms, it is 
mandatory that sponsor representatives (eg, study monitor) have direct access to original 
source documents (eg, paper or electronic patient records, patient charts, and laboratory 
reports) needed to verify the entries on case report forms.  During the review of these 
documents, the anonymity of the patient will be respected with strict adherence to 
professional standards of confidentiality.   
A study monitor will contact and visit the site regularly and will be allowed, on request at 
a mutually acceptable time, to inspect the various original medical records (paper or 
electronic) related to the study.  The study monitor will be responsible for inspecting the case 
report forms at regular intervals throughout the study, to verify the adherence to the protocol 
and the completeness and correctness of all case report form entries.  The investigator agrees 
to cooperate with the study monitor to ensure that any problems detected in the course of 
these monitoring visits are resolved.   


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Protocol MDV3800-14/TRIO029 
19 AUG 2016 – v2.0 FINAL 
 
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13.2.4 Study Audits 
During the course of the study and after study completion, it is likely that one or more quality 
assurance audits will be undertaken by authorized sponsor representatives.  The purpose of 
the audit is to ensure that the study is (or was) conducted and monitored in compliance with 
the protocol as well as recognized GCP guidelines and regulations.  These audits will also 
increase the likelihood that the study data and all other study documentation can withstand 
a regulatory authority inspection.  If such audits are to occur, they will be arranged for 
a reasonable and agreed upon time.  By signing this protocol, the investigator grants 
permission to the sponsor or designee to conduct onsite audits of all appropriate facilities and 
study documentation.   
13.3 Investigational Product Accountability 
The investigator must maintain accurate records of all study drug supplies received.  All 
records must be made available to the sponsor, authorized representatives, and appropriate 
regulatory agencies, upon request.   
Current ICH GCP guidelines require the investigator to ensure that study drug deliveries 
from the sponsor are received by a responsible person (eg, pharmacist), and the following: 
• 
That such deliveries are recorded, for example, on the sponsor’s drug accountability 
log or other sponsor-approved pharmacy log 
• 
That study drug is handled and stored safely and properly in accordance with the label 
and the study protocol 
• 
That study drug is only administered or dispensed to study patients in accordance 
with the protocol 
• 
That any used or unused drug is returned by the patient at each required visit 
• 
That any unused study drug is returned to the sponsor-designated facility or standard 
procedures for the alternative disposition of unused study drug are followed and only 
after approval by the sponsor representative 
Drug inventory and accountability records for the study drugs will be kept by the 
investigator/pharmacist.  Study drug accountability throughout the study must be 
documented.  The following guidelines are therefore pertinent: 
• 
The investigator agrees not to supply study drug to any persons except the patients in 
this study.   
• 
The investigator/pharmacist will keep the study drugs in a pharmacy or other locked 
and secure storage facility under controlled storage conditions as required by the 
study drug label, accessible only to those authorized by the investigator to dispense 
these study drugs.   
• 
The investigator/pharmacist will maintain a study drug inventory.  The inventory will 
include details of material received and a clear record of when they were dispensed 
and to which patient.   


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Talazoparib 
Protocol MDV3800-14/TRIO029 
19 AUG 2016 – v2.0 FINAL 
 
Page 50 of 58 
• 
The investigator/pharmacist agrees to conduct a final drug supply inventory and to 
record the results of this inventory on the drug accountability record at the conclusion 
or termination of this study.  It must be possible to reconcile delivery records with 
those of used and returned study drug.  Any discrepancies must be accounted for.  
Appropriate forms of deliveries and returns must be signed by the person responsible.   
• 
Used or unused study drug may be destroyed at the study site according to standard 
institutional procedures if the sponsor agrees with the procedure, and after drug 
accountability has been conducted by the sponsor or representative, unless otherwise 
approved.  A copy of the standard institutional procedure for destroying 
investigational drugs will be provided to the sponsor or designee upon request for 
review and approval before the first onsite destruction.  Unused study drug not 
destroyed at the site must be returned to the sponsor-designated facility at the end of 
the study or upon expiration.   
13.4 Compensation, Insurance, and Indemnity 
In the event of a side effect or injury, appropriate medical care as determined by the 
investigator or designated alternate will be provided.   
If bodily injury is sustained, resulting directly from the use of the study drug or by required 
study procedures, the sponsor will reimburse for reasonable physician fees and medical 
expenses necessary for treatment of only the bodily injury that is not covered by the patient’s 
medical or hospital insurance, provided that the injury is not due to a negligent or wrongful 
act or omission by the study doctor and study staff.  No other compensation of any type will 
be provided by the sponsor.  Financial compensation for lost wages, disability, or discomfort 
due to the study participation or procedures is not available.   
13.5 Retention of Records 
The investigator must make original study data (paper or electronic) accessible to the study 
monitor, other authorized sponsor representatives, and regulatory agency inspectors 
(eg, US FDA) upon request.  A file for each patient must be maintained that includes the 
signed informed consent form and copies of all source documentation related to that patient.  
The investigator must ensure the reliability and availability of source documents from which 
the information on the case report form was derived.   
Patient identity information recorded will be maintained for at least 15 years on the patient 
confidentiality log or longer if required by local regulations.   
Investigators must maintain all study documentation for at least 2 years following the 
approval of the drug, or until 2 years after the investigational drug program is discontinued, 
or longer if required by local regulations.  Study documentation includes all essential 
documents as defined in ICH E6 Guidelines for Good Clinical Practice.  The sponsor or 
designee will notify the investigator when any records may be discarded, but investigators 
must comply with local regulations.   


Medivation, Inc. 
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Protocol MDV3800-14/TRIO029 
19 AUG 2016 – v2.0 FINAL 
 
Page 51 of 58 
13.6 Study Termination 
The sponsor will terminate this study following completion of the study objectives, or earlier 
if deemed necessary.   
The sponsor reserves the right to terminate the study anytime.  When the sponsor is aware of 
information on matters concerning the quality, efficacy, and safety of the study drug, as well 
as other important information that may affect proper conduct of the clinical study, the 
sponsor may terminate the study and send a written notice of the termination along with the 
reasons to the investigator.   
If an investigator or the investigator’s EC intends to terminate participation in the study, the 
investigator must immediately inform the sponsor and provide the reason for it.   
14 USE OF STUDY INFORMATION AND PUBLICATION 
The results of this study will be published or presented at scientific meetings in a timely, 
objective, and clinically meaningful manner that is consistent with good science, industry and 
regulator guidance, and the need to protect the intellectual property of Medivation (sponsor), 
regardless of the outcome of the trial.  The data generated in this clinical trial are the 
exclusive property of the sponsor and are confidential.  Written approval from the sponsor is 
required before disclosing any information related to this clinical trial, and no publications 
initiated by investigators may be published until all protocol-defined primary and secondary 
endpoints are published in a manuscript.  Every attempt will be made to minimize the 
interval between the completion of data analysis and publication of the study results.  
Recommendations for the timing of presentation of trial endpoint data and the publication 
venues (congresses/journals) will be given by the sponsor’s Publications Steering 
Committee.   
Each investigator agrees to submit all manuscripts or congress abstracts and 
posters/presentations to the sponsor prior to submission.  This allows the sponsor to protect 
proprietary information, provide comments based on information from other studies that may 
not yet be available to the investigator, and ensure scientific and clinical accuracy.  The 
details of the processes of producing and reviewing reports, manuscripts, and presentations 
based on the data from this trial will be presented in the investigator’s clinical study 
agreement.   
In accord with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter trials only in their entirety and not as individual center data.  
In this case, a coordinating investigator and lead author will be designated by mutual 
agreement.   
Any formal publication of the study in which input of sponsor personnel exceeded that of 
conventional monitoring will be considered as a joint publication by the investigator and the 
appropriate sponsor personnel.  Authorship will be determined by mutual agreement and all 
authors must meet the criteria for authorship established by the International Committee of 
Medical Journal Editors (ICMJE) Uniform Requirements for Manuscripts or stricter local 


Medivation, Inc. 
Talazoparib 
Protocol MDV3800-14/TRIO029 
19 AUG 2016 – v2.0 FINAL 
 
Page 52 of 58 
criteria (ICMJE, 2015).  The sponsor does not compensate for authorship of a publication and 
all authors will be required to disclose, as part of the publication submission, any potential 
conflicts of interest, including pertinent financial or personal relationships with the sponsor 
or related entities, including sponsors of competing products that might be perceived to be 
a source of bias.  Authorship is decided on an individual basis and the sponsor’s Publications 
Steering Committee and sponsor representatives will mutually determine authors and their 
sequence on individual publications based on the relative contribution of each author to the 
study and/or publication.   
Investigators in this study agree to have their name listed as an investigator in any 
publication reporting results from this study, whether or not they are an author on the 
publication.   
Professional medical writing support is permissible, and any writing support will be 
acknowledged in each applicable publication, explaining the role the professional writer had 
in the drafting of the publication.  Medical writing and publications support funded by the 
sponsor on behalf of investigator authors will be considered as a transfer of value under the 
reporting requirements of Section 6002 of the Patient Protection Affordable Care Act 
(PPACA, 2010).  Transfer of value will be allocated to authors following sponsor guidelines.   


Medivation, Inc. 
Talazoparib 
Protocol MDV3800-14/TRIO029 
19 AUG 2016 – v2.0 FINAL 
 
Page 53 of 58 
15 REFERENCES 
Cardnell RJ, Feng Y, Diao L, Fan YH, Masrorpour F, Wang J, et al. Proteomic markers of DNA repair and 
PI3K pathway activation predict response to the PARP inhibitor BMN 673 in small cell lung cancer. 
Clin Cancer Res. 2013 Nov 15;19(22);6322-8. 
de Bono JS, Mina LA, Gonzalez M, Curtin NJ, Wang E, Henshaw JW, et al. First-in-human trial of novel oral 
PARP inhibitor BMN 673 in patients with solid tumors [abstract]. J Clin Oncol. 
2013 May 20;31(15 Suppl):2580. 
Goodin S, Griffith N, Chen  B, Chuk K, Daouphars M, Doreau C, et al. Safe handling of oral chemotherapeutic 
agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Pract. 
2011 Jan;7(1):7–12. 
International Committee of Medical Journal Editors (ICMJE). Recommendations for the conduct, reporting, 
editing, and publication of scholarly work in medical journals [Internet]. 2015 Dec [cited 2016 Aug 16]. 
Available from: http://www.icmje.org 
Murai J, Huang SY, Renaud A, Zhang Y, Ji J, Takeda S, et al. Stereospecific PARP trapping by BMN 673 and 
comparison with olaparib and rucaparib. Mol Cancer Ther. 2014 Feb;13(2):433-43. 
Murai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, et al. Trapping of PARP1 and PARP2 by 
clinical PARP inhibitors. Cancer Res. 2012 Nov 1;72(21):5588-99. 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of 
the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. 
Patient Protection and Affordable Care Act of 2010 [PPACA]. Section 6002: Transparency reports and 
reporting of physician ownership or investment interests. Pub. L. 111-148, 124 Stat. 119 (Mar. 23, 2010) [cited 
2016 Aug 16]. In: gpo.gov [Internet]. Available from: http://www.gpo.gov/fdsys/pkg/PLAW-
111publ148/pdf/PLAW-111publ148.pdf 
Shen Y, Aoyagi-Scharber M, Wang B. Trapping poly(ADP-ribose) polymerase. J Pharmacol Exp Ther. 
2015 Jun;353(3):446-57.  
Shen Y, Rehman FL, Feng Y, Boshuizen J, Bajrami I, Elliott R, et al. BMN 673, a novel and highly potent 
PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res. 
2013 Sep 15;19(18):5003-15. 
Wang B, Chu D, Feng Y, Shen Y, Aoyagi-Scharber M, Post LE. Discovery and characterization of (8S, 9R)-5-
Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-
de]phthalazin-3-one (BMN 673, talazoparib), a novel, highly potent, and orally efficacious poly(ADP-ribose) 
polymerase-1/2 inhibitor as an anticancer agent. J Med Chem. 2016 Jan 14;59(1):335-57. 


Medivation, Inc. 
Talazoparib 
Protocol MDV3800-14/TRIO029 
19 AUG 2016 – v2.0 FINAL 
 
Page 54 of 58 
16 INVESTIGATOR SIGNATURE 
 
MEDIVATION, INC. 
A Phase 1, Open-Label Study to Assess the Effects of Talazoparib on Cardiac 
Repolarization in Patients With Advanced Solid Tumors 
Signature of Agreement for Protocol MDV3800-14 Amendment 1 – 19 Aug 2016 
I have read this protocol and agree to conduct the study as outlined herein, in accordance 
with Good Clinical Practice and the Declaration of Helsinki, and complying with the 
obligations and requirements of clinical investigators and all other requirements listed 
in 21 CFR Part 312. 
 
 
 
Print Study Site Name 
 
Study Site Number 
Print Investigator Name 
 
 
Investigator Signature 
 
Date 


Medivation, Inc. 
Talazoparib 
Protocol MDV3800-14/TRIO029 
19 AUG 2016 – v2.0 FINAL 
 
Page 55 of 58 
Appendix 1: Study Schedule of Activities:  Screening 
Study Day 
-29 to -2 
Comments 
General Activities 
 
 
Informed consent and screen number 
X 
Obtain before performing any study-specific procedures.  Ensure consent is on the current version of the 
form approved by the ethics committee.  May obtain before the screening window.   
Demographics, medical history 
X 
 
Eligibility criteria 
X 
 
Enrollment authorization 
X 
Obtain approval for the enrollment from the sponsor or designee before proceeding to day -1.   
12-lead electrocardiogram 
X 
Obtain after supine for 10 minutes, read locally to determine eligibility, and submit to the central facility.   
Vital signs 
X 
Measure blood pressure (after supine for 5 minutes), heart rate, respiratory rate, and temperature.   
ECOG performance status 
X 
 
Physical examination, weight, height 
X 
Assess systems (eg, general appearance, head, eyes, ears, nose, mouth, skin, heart, lungs, lymph nodes, 
gastrointestinal, genitourinary, neurologic, and skeletal).   
Pretreatment-emergent serious 
adverse events review 
X 
Report serious adverse event information from time of signed informed consent through screen failure.   
Prior and concomitant medications 
X 
 
Laboratory Evaluations 
 
Refer to the central laboratory instruction manual for sample processing and for estimated turnaround 
time for results.  All laboratory evaluations will be tested centrally.   
Serum chemistry, hematology 
X 
 
Serum pregnancy test 
X 
For women of childbearing potential only.   
Blood sample for banking 
X 
Collect blood sample to be stored for reflex testing for HBV (HBsAg, anti-HBc) and HCV 
(HCV antibody, reflex testing for HCV RNA if positive).   
anti-HBc, hepatitis B core antibody; ECOG, Eastern Cooperative Oncology Group; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, 
hepatitis C virus.   
 


Medivation, Inc. 
Talazoparib 
Protocol MDV3800-14/TRIO029 
19 AUG 2016 – v2.0 FINAL 
 
Page 56 of 58 
Appendix 2: Study Schedule of Activities:  Treatment 
Study Period or Visit 
Treatment 
Unscheduled [1] 
Safety Follow-Up [2] 
Study Day 
-1 
1 
2 
3 to 21 
8 
15 
22 
Varies 
Varies 
Window (Days) 
na 
[3] 
na 
na 
±3 
±3 
±3 
na 
-3 to +10 
Enrollment ID number 
X 
 
 
 
 
 
 
 
 
General Activities 
 
 
 
 
 
 
 
 
 
Continuous ECG with Holter monitor [3] 
X 
X 
X 
 
 
 
X 
 
 
12-Lead ECG [4] 
 
 
 
 
 
 
 
 
X [4] 
Vital signs [5] 
X 
X 
X 
 
X 
X 
X 
X 
X 
Physical examination, weight [6] 
X [6] 
 
 
 
 
 
X 
X 
X 
ECOG performance status 
X 
 
 
 
 
 
X 
 
X 
Adverse events review [7] 
X 
X 
X 
 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
 
X 
X 
X 
X 
X 
Study drug treatment [8] 
 
X 
X 
X 
X 
X 
X 
 
 
Study drug accountability 
 
X 
 
 
X 
X 
X 
X (optional) 
 
Laboratory Evaluations [9] 
 
 
 
 
 
 
 
 
 
Serum chemistry, hematology 
 
X 
 
 
X 
X 
X 
X [1] 
X 
Blood sample for PK [10] 
 
X 
X 
 
 
 
X 
 
 
Pregnancy test [11] 
 
 
 
 
 
 
 
 
X 
[1] 
Anytime necessary to assess or follow up adverse events, at the patient’s request, or per investigator decision.   
[2] 
Safety follow-up occurs approximately 30 days after the last dose of study drug or before initiation of a new antineoplastic therapy, whichever occurs 
first.  Phone patients for adverse event follow-up if they do not come to the clinic.  For patients who enroll and initiate continued talazoparib treatment 
in a separate open-label extension study within 30 days after the last dose of talazoparib, safety follow-up will be omitted; an ECG will be obtained at 
the time of enrollment in the open-label extension study.   
[3] 
On day -1 (time 0, corresponding to the dosing time on day 1), apply Holter monitor and record ECGs for 6 hours.  On day 1 (within 72 hours of 
time 0 on day -1, corresponding to the clock time of the first baseline ECG measurement), start recording ECGs at least 45 minutes before time 0, 
administer the first dose of study drug at time 0, and continue recording ECGs for 6 hours postdose.  On day 2 (24 hours after the first dose of study 
drug), start recording ECGs at least 30 minutes before day 2 dose.  On day 22, start recording ECGs at least 45 minutes before time 0, administer study 
drug at time 0, and continue recording ECGs for 6 hours postdose.  (Appendix 3)   
[4] 
Obtain a single 12-lead ECG (after supine for 10 minutes); obtain at the time of enrollment in the open-label extension study for patients who enroll in 
that study within 30 days.   


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Page 57 of 58 
[5] 
Measure blood pressure (after supine for 5 minutes), heart rate, respiratory rate, and temperature at each visit.  On days -1, 1, 2, and 22, measure blood 
pressure (after supine for 5 minutes) 15 to 20 minutes before each PK time point (Appendix 3).   
[6] 
Assess systems (eg, general appearance, head, eyes, ears, nose, mouth, skin, heart, lung, lymph nodes, gastrointestinal, genitourinary, neurologic, and 
skeletal) per standard of care at the study site or as clinically indicated by symptoms.  Measure weight.  May be skipped on day -1 if performed within 
prior 7 days.   
[7] 
Collect serious adverse event information from the time of signed informed consent through approximately 30 days after the last dose of study drug, 
before a new antineoplastic therapy, or enrollment in the open-label extension study, whichever occurs first.  Collect nonserious adverse event 
information from day 1 through approximately 30 days after the last dose of study drug, before initiation of a new antineoplastic therapy, or 
enrollment in the open-label extension study, whichever occurs first.   
[8] 
Administer talazoparib at the study site on days 1, 2, and 22; administer talazoparib on days 2 and 22 at the same clock time as time 0 (±1 hour) on 
day 1.  Instruct patient to self-administer talazoparib at approximately the same time each morning on day 3 through day 21.   
Patients will fast for at least 6 hours before and 2 hours after the dose on days 1 and 22.  Patients may resume eating after the 2-hour postdose PK 
sample is collected.  On other days, talazoparib may be taken with food or without food.   
[9] 
Refer to the central laboratory instruction manual for sample processing and for estimated turnaround time for laboratory results.   
[10] 
Collect blood samples for PK on day 1 immediately before the first dose of study drug and at 1, 2, 4, and 6 hours postdose; on day 2 at 24 hours after 
the first dose of study drug (and before day 2 dose); and on day 22 predose and at 1, 2, 4, and 6 hours postdose.  After obtaining vital signs, patient 
should remain supine for 10-15 minutes before collecting blood sample for PK (Appendix 3).   
[11] 
For women of childbearing potential only.  Perform urine or serum pregnancy test either locally or using a centrally provided kit with a minimum 
sensitivity of 25 IU/L or equivalent units human chorionic gonadotropin.  Discontinue study drug treatment if a pregnancy test is positive.   
ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; ID, identification; na, not applicable; PK, pharmacokinetics.   


Medivation, Inc. 
Talazoparib 
Protocol MDV3800-14/TRIO029 
19 AUG 2016 – v2.0 FINAL 
 
Page 58 of 58 
Appendix 3: Time Points for ECG, Blood Pressure, and PK Assessments 
Day 
Time Point 
Blood 
Pressure [1] 
PK [2] 
-1 
Attach Holter monitor at time 0 (no dose) [3], [4] 
X 
 
 
1 hour 
X 
 
 
2 
X 
 
 
4 
X 
 
 
6 
X 
 
1 
Patients will fast for ≥ 6 hours before and 2 hours after day 1 dose 
 
 
 
Attach Holter monitor ≥ 45 minutes before time 0 [3] 
 
 
 
Time 0 (first dose of talazoparib, within 72 hours of day -1 time 0) 
X 
X 
 
1 hour postdose 
X 
X 
 
2 
Patients may resume eating after PK sample is collected 
X 
X 
 
4 
X 
X 
 
6 
X 
X 
2 
Attach Holter monitor ≥ 30 minutes before time 0 [3], [4] 
 
 
 
Time 0 (dose of talazoparib) 
X 
X 
22 
Patients will fast for ≥ 6 hours before and 2 hours after day 22 dose 
 
 
 
Attach Holter monitor ≥ 45 minutes before time 0 [3], [4] 
 
 
 
Time 0 (dose of talazoparib) 
X 
X 
 
1 hour postdose 
X 
X 
 
2 
Patients may resume eating after PK sample is collected 
X 
X 
 
4 
X 
X 
 
6 
X 
X 
[1] At 15-20 minutes before each PK time point, measure blood pressure (after supine for 5 minutes).   
[2] After obtaining blood pressure, patient should remain supine for 10 to 15 minutes before collecting 
blood sample for PK.   
[3] ECG recordings on days -1, 1, 2, and 22 are continuous ECG recordings by Holter monitor.   
[4] Time 0 corresponds to the dosing time on day 1.  Administer the dose of talazoparib on days 2 
and 22 at the same clock time as time 0 (±1 hour) on day 1.   
ECG, electrocardiogram; PK, pharmacokinetics.   
 

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Protocol MDV3800-14  Statistical Analysis Plan 
 
Page 6 
 
1. VERSION HISTORY 
This Statistical Analysis Plan (SAP) for study MDV3800-14 is based on the protocol 
amendment 1 dated 19AUG2016. 
Table 1 Summary of Major Changes in SAP Amendments 
SAP Version 
Change 
Rationale 
1.0 
 
 
2. INTRODUCTION 
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study MDV3800-14. 
The data will be analyzed by Medivation (a wholly owned subsidiary of Pfizer Inc.) and ERT 
Inc. (a designated CRO). 
All analyses stated in this Statistical Analysis Plan will be performed using SAS® software 
version 9.4 or later. 
2.1. Study Design 
This is a phase 1, open-label safety study of talazoparib (also known as MDV3800, BMN 
673), a poly(ADP-ribose) polymerase (PARP) inhibitor in development for treatment of a 
variety of human cancers. This study is designed to evaluate the effects of talazoparib on 
cardiac repolarization in at least 30 patients with advanced solid tumors with no available 
standard treatment options. Eligible patients will have continuous 12-lead electrocardiogram 
(ECG) recordings at baseline (day -1); time-matched pharmacokinetic (PK) samples and 
continuous ECG recordings will be obtained at days 1, 2, and 22; single ECGs will be 
collected at screening and safety follow-up. Patients will fast for at least 6 hours before and 2 
hours after the dose on days 1 and 22. 
On day -1, patients will have continuous 12-lead ECG recording, starting at time 0 (baseline, 
corresponding to the dosing time on day 1) and continuing for 6 hours. On day 1, within 72 
hours of time 0, continuous 12-lead ECG recording will start 45 minutes before 
administration of talazoparib 1 mg at time 0, and continue through 6 hours postdose. Blood 
samples for PK will be collected predose and at 1, 2, 4, and 6 hours postdose. On day 2 (24 
hours after the first dose of study drug), a 30-minute continuous 12-lead ECG recording and 
a blood sample for PK will be obtained before the day 2 dose of talazoparib. On days 3 to 21, 
talazoparib at 1 mg/day every day will be self-administered orally. On days 8 and 15, patients 
will return for general assessments. 
On day 22, patients will return for steady-state continuous 12-lead ECG recordings, starting 
45 minutes before the dose of talazoparib, and continuing for 6 hours postdose. PK samples 
will be collected predose and at 1, 2, 4, and 6 hours postdose. 
ECG data from continuous 12-lead ECG recordings will be submitted for independent central 
review. After reviewing for data quality, triplicate 10-second ECGs will be extracted from a 
5-minute extraction window at each planned time point, beginning 15 minutes before each 


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Protocol MDV3800-14  Statistical Analysis Plan 
 
Page 14 
 
Correction formulae included are QTcF and QTcB. The corrected QT intervals, QTcB and 
QTcF, are defined as: 
QTcF is the length of the QT interval corrected for heart rate by Fridericia’s formula: 
• QTcF = QT/(RR)1/3 
QTcB is the length of the QT interval corrected for heart rate by Bazett’s formula: 
• QTcB = QT/(RR)1/2 
5.4. Standard Derivations and Reporting Conventions 
Descriptive statistics (the number of patients [n], mean, standard deviation [SD], median, 
minimum, and maximum) will be used to summarize continuous variables. Means will be 
presented to 1 more decimal place than the recorded data. Medians will be presented using 
the same number of decimal places as the recorded data unless the calculated median results 
in an additional decimal place ending in ‘5’ (ie, 5 and 7 = 6, 5 and 8 = 6.5, etc). Standard 
deviations will be presented to 2 more decimal places than the recorded data. Minimum and 
maximum values will be presented using the same number of decimal places as the recorded 
data. 
Frequency distributions (number [n] and percentage of patients [%]) will be used to 
summarize categorical or qualitative variables. In general, the denominator for the percentage 
calculation will be based upon the total number of patients in the study population for that 
particular time point assessment. Records that are missing or not done will not be factored 
into the percentage calculation, unless otherwise specified. 
Percentages will be presented to a maximum of 1 decimal place. 
Unless otherwise specified, the following conventions will be applied to all analyses: 
• 1 year = 365.25 days. Year is calculated as (days/365.25) rounded up to 1 significant 
digit 
• 1 month = 30.4375 days. Month is calculated as (days/30.4375) rounded up to 1 
significant digit 
• Age will be calculated as the integer relative to the patient’s signed informed consent 
date and Date of Birth. 
• 1 pound = 0.454 kg 
• 1 inch = 2.54 cm 
• Missing data will not be imputed unless otherwise specified 
• For laboratory results collected as < or > for a numeric value, 0.0000000001 will be 
subtracted or added, respectively, to the value 


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Protocol MDV3800-14  Statistical Analysis Plan 
 
Page 20 
 
Therefore, the data will be presented as the frequency and percent of patients with each type 
of outlier. The following criteria (“study endpoints”) are defined for this analysis (“new” 
means not present at baseline, and becomes present on at least 1 on-treatment ECG time 
point) where “baseline” is defined as the time-averaged value based on the mean of all ECGs 
on day -1 and predose from day 1: 
Heart rate: A value for a patient is considered to be an outlier at pre-defined post dose time 
point if the heart rate measurement at that time point is < 50 beats per minute (bpm) and 
the measure is at least a 25% decrease from the patient’s baseline mean heart rate (i.e., a 
bradycardic event) or if the heart rate measurement at the pre-defined post dose time point 
is > 100 bpm and the measure is at least a 25% increase from the baseline mean heart rate 
(i.e., a tachycardic event). 
PR interval: A value for a patient is considered to be an outlier at a pre-defined post dose 
time point if the PR interval at that time point is > 200 msec and it is at least a 25% 
increase from the patient’s baseline mean PR interval. 
QRS interval: A value for a patient is considered to be an outlier at a pre-defined post dose 
time point if the QRS interval at  that time point is > 100 msec and it is at least a 25% 
increase from the patient’s baseline mean QRS interval. 
QT interval: A value for a patient is considered to be an outlier at a pre-defined post dose 
time point if the QT interval at that time point is > 500 msec and the patient’s baseline 
mean QT interval is ≤ 500 msec. 
QTcB: A value for a patient is considered to be an outlier at a pre-defined post dose time 
point if the QTcB interval at that time point is > 500 msec and the patient’s baseline mean 
QTcB interval is ≤ 500 msec. A value is also considered an outlier if the QTcB interval at 
a pre-defined post dose time point is > 480 msec when the patient’s baseline mean QTcB 
interval is ≤ 480 msec and when the QTcB interval at a pre-defined post dose time point 
is > 450 msec when the patient’s baseline mean QTcB interval is ≤ 450 msec. In addition, 
the number and percentage of patients with changes from baseline of > 30-60 msec and > 
60 msec are presented. 
QTcF: A value for a patient is considered to be an outlier at a pre-defined post dose time 
point if the QTcF interval at that time point is > 500 msec and the patient’s baseline mean 
QTcF interval is ≤ 500 msec. A value is also considered an outlier if the QTcF interval at 
a pre-defined post dose time point is > 480 msec when the patient’s baseline mean QTcF 
interval is ≤ 480 msec and when the QTcF interval at a pre-defined post dose time point is 
> 450 msec when the patient’s baseline mean QTcF interval is ≤ 450 msec. In addition, 
the number and percentage of patients with changes from baseline of > 30-60 msec and > 
60 msec are presented. 
A categorical or outlier analysis is considered exploratory since the study is not powered to 
pick up unusual individual responses to the potential effects of drugs. The categorical 
analysis is assessed using the time-averaged baseline, comparing this baseline ECG interval 
value to all post-treatment ECG time points and then choosing the value that is the largest 


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Protocol MDV3800-14  Statistical Analysis Plan 
 
Page 26 
 
The PK analyses will include descriptions of the PK by days. Selected PK parameters will be 
summarized, such as maximum plasma concentration (Cmax), time to maximum plasma 
concentration (Tmax), concentration at 24 hours (C24h), area under the plasma concentration 
time-curve (AUC24h), AUC accumulation ratio (AR) and apparent plasma clearance (CL/F). 
AUC24h on Day 22 will be calculated by imputing Day 22 24 hour concentration to be the 
same as Day 22 predose concentration. 
PK parameters of talazoparib will be listed by patient and summarized descriptively by day 
for the PK population. Exclusion of values from the summary statistics calculations due to 
dose changes (eg, dose interruptions, dose reductions) will be handled on a case-by-case 
basis. The following descriptive statistics of individual analytes will be provided for all PK 
parameters except Tmax: n, arithmetic mean, SD, CV%, geomean, geoCV%, median, 
minimum, and maximum. For Tmax, only n, median, minimum, and maximum will be 
reported. Descriptive statistics will be calculated only for PK parameters obtained from n ≥ 3. 
7. SAMPLE SIZE CONSIDERATIONS 
A sample size of at least 27 evaluable patients will provide 80% power to reject the null 
hypothesis if the mean change from baseline in QTcF is ≥ 10 msec with  one-sided  5% level 
of significance, assuming a standard deviation of 20 msec. To allow for 10% dropouts, 30 
patients will be enrolled. 
Patients will be enrolled until 30 patients complete day 22, miss ≤ 5 consecutive doses of 
study drug, have technically adequate ECG recordings, and have at least 80% of specified PK 
samples collected  representing all 3-days of observation (days 1, 2 and 22). 
8. INTERIM ANALYSES 
N/A 
9. REFERENCES  
No literature reference is cited. 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 27 
 
10. APPENDICES 
Appendix 1. Clinical Study Report Tables, Listings, and Figures 
CSR TLF No.  
Title 
Analysis Population 
Analysis Performed by? 
Tables 
14.1.1 
Patient Disposition 
Safety Population 
MDVN/PFE 
14.1.2 
Analysis Populations 
Enrolled Population 
MDVN/PFE 
14.1.3.1 
Demographics and Baseline Characteristics  
Safety Population 
MDVN/PFE 
14.1.3.2 
Baseline Disease Characteristics  
Safety Population 
MDVN/PFE 
14.1.4 
Medical History by System Organ Class and Preferred Term  
Safety Population 
MDVN/PFE 
14.1.5.1 
Treatment Exposure and Compliance  
Safety Population 
MDVN/PFE 
14.1.5.2 
Concomitant Medications by ATC Class and Preferred Term  
Safety Population 
MDVN/PFE 
14.3.1.1 
Overview of Treatment-Emergent Adverse Events  
Safety Population 
MDVN/PFE 
14.3.1.2 
Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
MDVN/PFE 
14.3.1.3 
Treatment-Emergent Adverse Events by Preferred Term  
Safety Population 
MDVN/PFE 
14.3.1.4 
Treatment-Emergent Adverse Events Related to Study Drug by Preferred Term  
Safety Population 
MDVN/PFE 
14.3.1.5 
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, and 
Maximum Severity  
Safety Population 
MDVN/PFE 
14.3.2.1 
Serious Adverse Events by System Organ Class and Preferred Term  
Safety Population 
MDVN/PFE 
14.3.2.2 
Serious Adverse Events Related to Study Drug by Preferred Term 
Safety Population 
MDVN/PFE 
14.3.2.3 
Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation by 
System Organ Class and Preferred Term 
Safety Population 
MDVN/PFE 
14.3.4.1 
Hematology Shift Table by Worst Postbaseline Toxicity Grade  
Safety Population 
MDVN/PFE 
14.3.4.2 
Chemistry Shift Table  by Worst Postbaseline Toxicity Grade  
Safety Population 
MDVN/PFE 
14.3.4.3 
Hematology Shift Table Based on Normal Range  
Safety Population 
MDVN/PFE 
14.3.4.4 
Chemistry Shift Table Based on Normal Range  
Safety Population 
MDVN/PFE 
14.3.4.5 
Change from Baseline Hematology Laboratory Result  
Safety Population 
MDVN/PFE 
14.3.4.6 
Change from Baseline Chemistry Laboratory Result  
Safety Population 
MDVN/PFE 
14.3.4.7 
Treatment-Emergent Liver Test Elevations  
Safety Population 
MDVN/PFE 
14.3.5.1 
Change From Baseline Vital Sign Results  
Safety Population 
MDVN/PFE 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 28 
 
CSR TLF No.  
Title 
Analysis Population 
Analysis Performed by? 
14.3.5.2 
Clinically Notable Changes in Vital Sign Results 
Safety Population 
MDVN/PFE 
14.3.6 
Change from Baseline ECG Results 
Safety Population 
MDVN/PFE 
14.3.6.1.1 
Time-Matched and Time-Averaged ECG Central Tendency and Outlier Analyses - 
Heart Rate (bpm) 
Electrocardiographic Population 
ERT 
14.3.6.1.2 
Time-Matched and Time-Averaged ECG Central Tendency and Outlier Analyses - 
PR Interval (msec) 
Electrocardiographic Population 
ERT 
14.3.6.1.3 
Time-Matched and Time-Averaged ECG Central Tendency and Outlier Analyses - 
QRS Interval (msec) 
Electrocardiographic Population 
ERT 
14.3.6.1.4 
Time-Matched and Time-Averaged ECG Central Tendency and Outlier Analyses - 
QT Interval (msec) 
Electrocardiographic Population 
ERT 
14.3.6.1.5 
Time-Matched and Time-Averaged ECG Central Tendency and Outlier Analyses - 
QTc Fridericia (msec) 
Electrocardiographic Population 
ERT 
14.3.6.1.6 
Time-Matched and Time-Averaged ECG Central Tendency and Outlier Analyses - 
QTc Bazett (msec) 
Electrocardiographic Population 
ERT 
14.3.6.1.7 
Timepoint and Time-Averaged ECG Central Tendency and Outlier Analyses  QTc 
Individual (ms) 
Electrocardiographic Population 
ERT 
14.3.6.1.8 
Timepoint  and Time-Averaged  ECG Central Tendency and Outlier Analyses QTc 
Fridericia (ms) 
Electrocardiographic Population 
ERT 
14.3.6.2.1 
Treatment-Emergent Abnormalities – Atrial Fibrillation 
Electrocardiographic Population 
ERT 
14.3.6.2.2 
Treatment-Emergent Abnormalities – Atrial Flutter 
Electrocardiographic Population 
ERT 
14.3.6.2.3 
Treatment-Emergent Abnormalities - Second Degree Heart Block 
Electrocardiographic Population 
ERT 
14.3.6.2.4 
Treatment-Emergent Abnormalities - Third Degree Heart Block 
Electrocardiographic Population 
ERT 
14.3.6.2.5 
Treatment-Emergent Abnormalities - Complete Right Bundle Branch Block 
Electrocardiographic Population 
ERT 
14.3.6.2.6 
Treatment-Emergent Abnormalities - Complete Left Bundle Branch Block 
Electrocardiographic Population 
ERT 
14.3.6.2.7 
Treatment-Emergent Abnormalities - ST Segment Depression 
Electrocardiographic Population 
ERT 
14.3.6.2.8 
Treatment-Emergent Abnormalities - ST Segment Elevation 
Electrocardiographic Population 
ERT 
14.3.6.2.9 
Treatment-Emergent Abnormalities - Negative (Inverted) T Waves 
Electrocardiographic Population 
ERT 
14.3.6.2.10 
Treatment-Emergent Abnormalities - Myocardial Infarction Pattern 
Electrocardiographic Population 
ERT 
14.3.6.2.11 
Treatment-Emergent Abnormalities - Abnormal U Waves 
Electrocardiographic Population 
ERT 
14.3.6.3.1 
Change from Baseline with 90% Two-Sided Confidence Interval - QTc Fridericia 
(msec) 
Electrocardiographic Population 
ERT 
14.3.6.3.2 
Change from Baseline with 90% Two-Sided Confidence Interval - QTc Bazett 
(msec) 
Electrocardiographic Population 
ERT 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 29 
 
CSR TLF No.  
Title 
Analysis Population 
Analysis Performed by? 
14.4.1.1 
Concentration-ECG Interval Effect Analysis- Change from Baseline versus the 
Talazoparib Plasma Concentration – Estimates from Linear Mixed Model -QTc 
Fridericia, QTc Bazett Interval (msec)   
Safety Population 
ERT 
14.4.1.2 
Individual and Summary of Plasma Talazoparib Concentrations  
PK Population 
MDVN/PFE 
14.4.1.3 
Individual and Summary of Plasma Talazoparib PK Parameters on Day 1 
PK Analysis Population 
MDVN/PFE 
14.4.1.4 
Individual and Summary of Plasma Talazoparib PK Parameters on Day 22 
PK Analysis Population 
MDVN/PFE 
14.4.1.5 
Overall Summary of Plasma Talazoparib PK Parameters 
PK Analysis Population 
MDVN/PFE 
Figures 
14.3.6.1.1 
Mean Change from Baseline- Heart Rate (Values with Means ± 90% CIs - 
Estimates and CI are model based) 
Electrocardiographic Population 
ERT 
14.3.6.1.2 
Mean Change from Baseline- PR Interval (Values with Means ± 90% CIs - 
Estimates and CI are model based) 
Electrocardiographic Population 
ERT 
14.3.6.1.3 
Mean Change from Baseline- QRS Duration (Values with Means ± 90% CIs - 
Estimates and CI are model based) 
Electrocardiographic Population 
ERT 
14.3.6.1.4 
Mean Change from Baseline- QT Interval (Values with Means ± 90% CIs - 
Estimates and CI are model based) 
Electrocardiographic Population 
ERT 
14.3.6.1.5 
Mean Change from Baseline- QTcF Interval (Values with Means ± 90% CIs - 
Estimates and CI are model based) 
Electrocardiographic Population 
ERT 
14.3.6.1.6 
Mean Change from Baseline- QTcB Interval (Values with Means ± 90% CIs - 
Estimates and CI are model based) 
Electrocardiographic Population 
ERT 
14.4.1.1 
Change from Baseline QTcF Versus Mean Talazoparib Plasma Concentration 
Estimates from the Mixed Effects Model Regression 
Pharmacokinetic-Pharmacodynamic 
Population 
ERT 
14.4.1.2 
Change from Baseline QTcB Versus Mean Talazoparib Plasma Concentration 
Estimates from the Mixed Effects Model Regression 
Pharmacokinetic-Pharmacodynamic 
Population 
ERT 
14.4.1.3 
Mean (SD) Plasma Talazoparib Concentration-Time Profiles  
PK Population 
MDVN/PFE 
14.4.1.4 
Individual Plasma Talazoparib Concentration-Time Profiles for Day 1  
PK Population 
MDVN/PFE 
14.4.1.5 
Individual Plasma Talazoparib Concentration-Time Profiles for Day 22 
PK Population 
MDVN/PFE 
14.4.2.1 
Subject Profiles: Change from Baseline vs Talazoparib Plasma Conc. 
Individual (PK-PD Population) 
ERT 
14.4.2.2 
Subject Profiles: Change from Baseline vs Talazoparib Plasma Conc. 
Individual (PK-PD Population) 
ERT 
14.4.2.3 
Subject Profiles: Change from Baseline vs Talazoparib Plasma Conc. 
Individual (PK-PD Population) 
ERT 
14.4.2.4 
Subject Profiles: Change from Baseline vs Talazoparib Plasma Conc. 
Individual (PK-PD Population) 
ERT 
14.4.2.5 
Subject Profiles: Change from Baseline vs Talazoparib Plasma Conc. 
Individual (PK-PD Population) 
ERT 
14.4.2.6 
Subject Profiles: Change from Baseline vs Talazoparib Plasma Conc. 
Individual (PK-PD Population) 
ERT 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 30 
 
CSR TLF No.  
Title 
Analysis Population 
Analysis Performed by? 
Listings 
16.2.1.1 
Inclusion and Exclusion Criteria 
Screened Population 
MDVN/PFE 
16.2.1.2 
Patient Disposition 
Safety Population 
MDVN/PFE 
16.2.2 
Protocol Deviations 
Safety Population 
MDVN/PFE 
16.2.3 
Analysis Populations 
Enrolled Population 
MDVN/PFE 
16.2.4.1 
Baseline Demographics  
Safety Population 
MDVN/PFE 
16.2.4.2 
Baseline Disease Characteristics  
Safety Population 
MDVN/PFE 
16.2.4.3 
Medical History  
Safety Population 
MDVN/PFE 
16.2.4.4 
Prior Systemic Anti-Cancer Therapy  
Safety Population 
MDVN/PFE 
16.2.4.5 
Prior Radiation Therapy  
Safety Population 
MDVN/PFE 
16.2.4.6 
Prior Surgery for Cancer  
Safety Population 
MDVN/PFE 
16.2.5.1 
Dose Administration Record  
Safety Population 
MDVN/PFE 
16.2.5.2 
Drug Accountability  
Safety Population 
MDVN/PFE 
16.2.5.3 
Concomitant Medication  
Safety Population 
MDVN/PFE 
16.2.5.4 
Other Procedures 
Safety Population 
MDVN/PFE 
16.2.7.1 
Treatment-Emergent Adverse Events  
Safety Population 
MDVN/PFE 
16.2.7.2 
Serious Adverse Events 
Screening Failures 
MDVN/PFE 
16.2.7.3 
Deaths 
Enrolled Population 
MDVN/PFE 
16.2.8.1 
Hematology Laboratory Results  
Safety Population 
MDVN/PFE 
16.2.8.2 
Chemistry Laboratory Results  
Safety Population 
MDVN/PFE 
16.2.8.3 
Vital Sign Results  
Safety Population 
MDVN/PFE 
16.2.8.4.1 
ECG Results 
Safety Population 
MDVN/PFE 
16.2.8.4.2 
Listing of ECG Parameters -- Holter Extraction 
Safety Population 
ERT 
16.2.8.4.3 
Listing of ECG Morphology Interpretations -- Holter Extraction 
Safety Population 
ERT 
16.2.8.5 
Pregnancy Test Results  
Safety Population 
MDVN/PFE 
16.2.8.6 
Other Laboratory Results 
Safety Population 
MDVN/PFE 
16.2.8.7 
Individual Plasma Talazoparib Concentrations 
PK Population 
MDVN/PFE 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 31 
 
Appendix 2. Shells and Specifications 
Appendix 2.1. Section 14 Tables 
Table 14.1.1: Patient Disposition (Safety Population) 
Disposition 
  Reason 
Talazoparib 
1 mg 
(N = xx) 
  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Patients treated 
   Completed 
   Discontinued 
 
Primary reason for treatment discontinuation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Reason 1 
   Reason 2 
   Reason 3 
 
Is patient continuing open-label extension study? 
xx (xx.x%) 
xx (xx.x%) 
   Yes 
   No 
 
The date of analysis data transfer is DDMONYYYY. 
Percentage is based on N. 
Data source: Listing 16.2.1.2. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 32 
 
Table 14.1.2: Analysis Populations (All Enrolled) 
Analysis Set 
Talazoparib 
1 mg 
(N = xx) 
 
 
Safety population 
xx (xx.x%) 
 
 
ECG analysis population 
xx (xx.x%) 
 
 
PK population 
xx (xx.x%) 
 
 
PK analysis population 
xx (xx.x%) 
 
 
PK-PD analysis population 
xx (xx.x%) 
 
 
The date of analysis data transfer is DDMONYYYY. 
ECG: electrocardiogram, PD: pharmacodynamics, PK: pharmacokinetics 
The safety population includes all patients who receive any amount of talazoparib. 
The ECG analysis population consists of all enrolled patients who receive at least 1 dose of talazoparib, and have at least 1 available baseline 
and 1 on-treatment ECG data.  
The PK population is defined as all patients who receive at least 1 dose of talazoparib and provide at least 1 reportable concentration. 
The PK analysis population is defined as all patients who have sufficient concentration data to derive at least 1 PK parameter. 
The PK-PD analysis population is defined as all patients in the ECG analysis population who have at least 1 time-matched pair of plasma 
concentration and ECG measurements obtained at the same nominal time point. 
Percentage is based on N. 
Data source:  Listing 16.2.3. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 33 
 
Table 14.1.3.1: Demographics and Baseline Characteristics (Safety Population) 
Demographic 
  Variable 
Talazoparib 
1 mg 
(N = xx) 
Age (years) 
 
   n 
xxx 
   Mean (SD) 
xx.x (x.xx) 
   Median 
xx.x 
   Min, Max 
xx.x, xx.x 
 
 
Sex 
 
   Female 
xx (xx.x%) 
   Male 
xx (xx.x%) 
   Missing 
xx (xx.x%) 
 
 
Race 
 
   American Indian or Alaska Native 
xx (xx.x%) 
   Asian 
xx (xx.x%) 
   Black or African American 
xx (xx.x%) 
   Native Hawaiian or Other Pacific Islander 
xx (xx.x%) 
   White 
xx (xx.x%) 
   Other 
xx (xx.x%) 
   Missing 
xx (xx.x%) 
 
 
Ethnicity 
 
   Hispanic or Latino 
xx (xx.x%)  
   Not Hispanic or Latino 
xx (xx.x%)  
   Other 
xx (xx.x%)  
   Unknown 
xx (xx.x%)  
  
 
Weight (kg) 
 
   n 
xxx 
   Mean (SD) 
xx.x (x.xx) 
   Median 
xx.x 
   Min, Max 
xx.x, xx.x 
 
 
Height (cm) 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 34 
 
Demographic 
  Variable 
Talazoparib 
1 mg 
(N = xx) 
   n 
xxx 
   Mean (SD) 
xx.x (x.xx) 
   Median 
xx.x 
   Min, Max 
xx.x, xx.x 
 
 
Body mass index [BMI] (kg/m^2) 
 
   n 
xxx 
   Mean (SD) 
xx.x (x.xx) 
   Median 
xx.x 
   Min, Max 
 
 
 
The date of analysis data transfer is DDMONYYYY. 
SD:  standard deviation, Min: minimum, Max: maximum, n: counts of non-missing values. 
Percentage is based on N.  
Data source:  Listing 16.2.4.1. 
 
Programming Specification: 
• 
‘Missing’ is shown only if the count is not zero. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 35 
 
Table 14.1.3.2: Baseline Disease Characteristics (Safety Population) 
Disease 
  Characteristics 
Talazoparib 
1 mg 
(N = xx) 
 
 
Primary Cancer Site 
 
   Breast 
xx (xx.x%) 
   Colorectal 
xx (xx.x%) 
   Liver 
xx (xx.x%) 
   Lung 
xx (xx.x%) 
   Kidney 
xx (xx.x%) 
   Ovary 
xx (xx.x%) 
   Prostate 
xx (xx.x%) 
   Melanoma 
xx (xx.x%) 
   Other 
xx (xx.x%) 
 
 
Staging at Initial Diagnosis [1] 
 
   Primary Tumor: 
xx (xx.x%) 
      T0 
xx (xx.x%) 
      T1 
xx (xx.x%) 
      T2 
xx (xx.x%) 
      T3 
xx (xx.x%) 
      T4 
xx (xx.x%) 
      TX 
xx (xx.x%) 
   Regional Lymph Nodes: 
 
      N0 
xx (xx.x%) 
      N1 
xx (xx.x%) 
      N2 
xx (xx.x%) 
      N3 
xx (xx.x%) 
      NX 
xx (xx.x%) 
   Distant Metastases: 
 
      M0 
xx (xx.x%) 
      M1 
xx (xx.x%) 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 36 
 
Disease 
  Characteristics 
Talazoparib 
1 mg 
(N = xx) 
      MX 
xx (xx.x%) 
 
 
Histopathological Type at Initial Diagnosis 
 
   Adenocarcinoma 
xx (xx.x%) 
   Squamous Cell Carcinoma 
xx (xx.x%) 
   Other 
xx (xx.x%) 
 
 
ECOG performance status 
 
   0 
xx (xx.x%) 
   1 
xx (xx.x%) 
   2 
xx (xx.x%) 
   3 
xx (xx.x%) 
   4 
xx (xx.x%) 
 
 
The date of analysis data transfer is DDMONYYYY. 
Percentage is based on N.  
AJCC: American Joint Committee on Cancer, ECOG: Eastern Cooperative Oncology Group.  
[1] The Classification of Staging at Initial Diagnosis are as per AJCC Staging Manual Sixth Edition. 
Data source:  Listing 16.2.4.2. 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 37 
 
Table 14.1.4: Medical History by System Organ Class and Preferred Term (Safety Population) 
System Organ Class 
  Preferred Term 
Talazoparib 
1 mg 
(N = xx) 
Number of Patients Who Had at Least One Medical History 
xx (xx.x%) 
 
 
SOC 1 <- total> 
xx (xx.x%) 
   preferred term 1 
xx (xx.x%) 
   preferred term 2 
xx (xx.x%) 
   preferred term 3 
xx (xx.x%) 
 
 
SOC 2 <- total> 
xx (xx.x%) 
   preferred term 1 
xx (xx.x%) 
   preferred term 2 
xx (xx.x%) 
   preferred term 3 
xx (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
A patient with multiple occurrences of a given preferred term within a system organ class is counted once only in the total row. 
Preferred terms are sorted within system organ class in descending frequency and then alphabetically. 
Percentage is based on N. 
Data source:  Listing 16.2.4.3. 
 
Programming Specification: 
• 
System organ classes are presented in descending frequency and then alphabetically.   
• 
Preferred terms are sorted within system organ class in descending frequency and then alphabetically.   
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 38 
 
Table 14.1.5.1: Treatment Exposure and Compliance (Safety Population) 
Category 
Talazoparib 
1 mg 
(N = xx) 
Duration of Exposure (Days) 
   = 22 
xx (xx.x%) 
   < 22 
xx (xx.x%) 
 
 
Cumulative Dose (mg) 
 
   Mean (SD) 
xx.x (x.xx) 
   Median 
xx.x 
   Min, Max 
xx.x, xx.x 
 
 
Percent of Days Received Planned Dose [1] 
 
   = 100% 
xx (xx.x%) 
   80% -< 100% 
xx (xx.x%) 
   < 80% 
xx (xx.x%) 
 
 
Number of Capsules Taken [2] 
 
   Mean (SD) 
xx.x (x.xx) 
   Median 
xx.x 
   Min, Max 
xx.x, xx.x 
 
 
Percent of Compliance [3] 
 
   = 100% 
xx (xx.x%) 
   80% -< 100% 
xx (xx.x%) 
   < 80% 
xx (xx.x%) 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 39 
 
Category 
Talazoparib 
1 mg 
(N = xx) 
The date of analysis data transfer is DDMONYYYY. 
A patient is counted in one duration range only. 
SD: standard deviation, Min: minimum, Max: maximum. 
Percentage is based on N. 
[1] Denominator is defined as number of scheduled days of full dosing as per protocol. 
[2] Total number of capsules taken is calculated as the number of capsules dispensed at all visits minus the number of capsules returned. 
[3] Percent compliance is calculated as the number of capsules taken divided by the expected number of capsules taken, multiplied by 100. 
Data source:  Listing 16.2.5.1 and Listing 16.2.5.2. 
 
Programming Specification: 
• 
Duration of exposure in days = Last dosing date – First dosing date + 1 excluding dose interruptions.   
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 40 
 
Table 14.1.5.2: Concomitant Medications by ATC Class and Preferred Term (Safety Population) 
ATC Class 
   Preferred Term 
Talazoparib 
1 mg 
(N = xx) 
Number of Patients Who Had at Least One Concomitant Medication 
xx (xx.x%) 
 
 
ATC 1 <-total> 
xx (xx.x%) 
   preferred term 1 
xx (xx.x%) 
   preferred term 2 
xx (xx.x%) 
 
 
ATC 2 <-total> 
xx (xx.x%) 
   preferred term 1 
xx (xx.x%) 
   preferred term 2 
xx (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
ATC: anatomical therapeutic chemical classification system using the World Health Organization Drug Dictionary (WHO-DD). 
Medications are considered concomitant if taken during the treatment period. 
A medication can appear with more than one ATC class. 
A patient with multiple generic medication names within an ATC class is counted once only in the total row. 
ATC classes are presented in descending frequency and then alphabetically. Preferred terms are sorted within ATC class in descending frequency and 
then alphabetically. 
Percentage is based on N. 
Data source:  Listing 16.2.5.3. 
 
Programming Specification: 
• 
ATC classes are presented in descending frequency and then alphabetically.   
• 
Preferred terms are sorted within ATC class in descending frequency and then alphabetically.  
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 41 
 
Table 14.3.1.2: Overview of Treatment-Emergent Adverse Events (Safety Population) 
Category 
Talazoparib 
1 mg 
(N = xx) 
 
 
   Patients with at Least One AE 
xx (xx.x%) 
   Patients with at Least One AE Related to Study Drug 
xx (xx.x%) 
 
 
   Patients with at Least One AE of Grade 3 or Higher 
xx (xx.x%) 
   Patients with at Least One AE of Grade 3 or Higher Related to Study Drug 
xx (xx.x%) 
 
 
   Patients with at Least One SAE 
xx (xx.x%) 
   Patients with at Least One SAE Related to Study Drug 
xx (xx.x%) 
 
 
   Patients who died 
xx (xx.x%) 
 
 
   Patients who Discontinued from Study Treatment due to AEs 
xx (xx.x%) 
   Patients who Discontinued from Study Treatment due to SAEs 
xx (xx.x%) 
   Patients who had Study Treatment Interrupted due to AEs 
xx (xx.x%) 
 
 
The date of analysis data transfer is DDMONYYYY. 
AE: adverse event, SAE: serious adverse event. 
A patient with multiple occurrences of an event is counted once only in the AE category.  
Percentage is based on N. 
AE grades are evaluated per NCI-CTCAE version 4.03. 
Data source:  Listing 16.2.7.1. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 42 
 
Table 14.3.1.2: Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (Safety Population) 
System Organ Class 
  Preferred Term 
Talazoparib 
1 mg 
(N = xx) 
Number of Patients with at Least One AE 
xx (xx.x%) 
 
 
Vascular disorders <-total> 
xx (xx.x%) 
   preferred term 1 
xx (xx.x%) 
   preferred term 2 
xx (xx.x%) 
   preferred term 3 
xx (xx.x%) 
 
 
SOC 2 <-total> 
xx (xx.x%) 
   preferred term 1 
xx (xx.x%) 
   preferred term 2 
xx (xx.x%) 
   preferred term 3 
xx (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
AE: adverse event. 
Patients with multiple events for a given preferred term or system organ class are counted once only for each preferred term or system organ 
class, respectively. 
Preferred terms are sorted within system organ class in descending frequency and then alphabetically. 
Percentage is based on N. 
MedDRA version 19.1. 
Data source:  Listing 16.2.7.1. 
 
Programming Specification: 
• 
System organ classes are presented in descending frequency and then alphabetically.   
• 
Preferred terms are sorted within system organ class in descending frequency and then alphabetically.   
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 43 
 
Table 14.3.1.3: Treatment-Emergent Adverse Events by Preferred Term (Safety Population) 
Preferred Term 
Talazoparib 
1 mg 
(N = xx) 
Number of Patients with at Least One AE 
xx (xx.x%) 
 
 
preferred term 1 
xx (xx.x%) 
preferred term 2 
xx (xx.x%) 
preferred term 3 
xx (xx.x%) 
preferred term 4 
xx (xx.x%) 
preferred term 5 
xx (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
AE: adverse event. 
A patient with multiple occurrences of a given preferred term is counted once only. 
Preferred terms are sorted in descending frequency and then alphabetically. 
Percentage is based on N. 
MedDRA version 19.1. 
Data source:  Listing 16.2.7.1. 
 
Programming Specification: 
• 
Preferred terms are presented in descending frequency and then alphabetically.  
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 44 
 
Table 14.3.1.4: Treatment-Emergent Adverse Events Related to Study Drug by Preferred Term (Safety Population) 
Preferred Term 
Talazoparib 
1 mg 
(N = xx) 
Number of Patients with at Least One AE 
x (xx.x%) 
 
 
   preferred term 1 
x (xx.x%) 
   preferred term 2 
x (xx.x%) 
   preferred term 3 
x (xx.x%) 
   preferred term 4 
x (xx.x%) 
   preferred term 5 
x (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
AE: adverse event. 
A patient with multiple occurrences of a given preferred term is counted once only. 
Preferred terms are sorted in descending frequency and then alphabetically. 
Percentage is based on N. 
MedDRA version 19.1. 
Data source:  Listing 16.2.7.1. 
 
Programming Specification: 
• 
Preferred terms are sorted in descending frequency and then alphabetically. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 45 
 
Table 14.3.1.5: Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Severity 
(Safety Population) 
System Organ Class 
   Preferred Term 
Talazoparib 
1 mg 
(N = xx) 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Total 
Number of Patients with at Least One AE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Vascular disorders <-total> 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   preferred term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   preferred term 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
SOC 2 <-total> 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   preferred term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   preferred term 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
AE: adverse event. 
Patients with multiple events for a given preferred term or system organ class are counted once only for each preferred term or system organ 
class, respectively. 
System organ classes are presented in descending frequency of ‘Grade 1’ column, as reported in the ‘Total’ and then alphabetically.  Preferred terms are 
sorted within system organ class in descending frequency of ‘Grade 1’ column, as reported in the “Total”  and then alphabetically. 
Percentage is based on N. 
MedDRA version 19.1. 
AE grades are evaluated per NCI-CTCAE version 4.03. 
Data source:  Listing 16.2.7.1. 
 
Programming Specification: 
• 
System organ classes are presented in descending frequency of ‘Grade 1’ column, as reported in the ‘Total’ and then 
alphabetically.   
• 
Preferred terms are sorted within system organ class in descending frequency of ‘Grade 1’ column, as reported in the 
‘Total’ and then alphabetically. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 46 
 
Table 14.3.2.1: Serious Adverse Events by System Organ Class and Preferred Term (Safety Population) 
Table 14.3.2.2: Serious Adverse Events Related to Study Drug by Preferred Term (Safety Population) 
Table 14.3.2.3: Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation by System Organ Class and 
Preferred Term (Safety Population) 
 
Programming Specification:  
For Table 14.3.2.1 and Table 14.3.2.3: Follow similar structure to Table 14.3.1.2. 
For Table 14.3.2.2: Follow similar structure to Table 14.3.1.4. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 47 
 
Table 14.3.4.1: Hematology Shift Table by Worst Postbaseline Toxicity Grade (Safety Population) 
 Baseline [1] 
Worst Post-baseline Toxicity Grade [2] 
Category 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Missing 
 
 
 
 
 
 
 
 
Talazoparib 1 mg (N = xx) 
 
 
 
 
 
 
 
Grade 0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Missing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Total 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
The date of analysis data transfer is DDMONYYYY. 
Percentage is based on N. 
Toxicity grading is per NCI-CTCAE version 4.03. 
[1] Baseline is defined as the last non-missing value prior to the first dose. 
[2] Based on all test results collected in the treatment-emergent period. For each parameter, patients are counted once only at the worst grade. 
Data source:  Listing 16.2.8.1. 
 
Programming Specification: 
• 
Include all hematology parameters specified in the protocol without CTC grades (where applicable), output one 
parameter for each file.   
• 
Post-baseline laboratory assessments include both scheduled and unscheduled visits. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 48 
 
Table 14.3.4.2: Chemistry Shift Table by Worst Postbaseline Toxicity Grade (Safety Population) 
Baseline [1] 
Worst Post-baseline Toxicity Grade [2] 
Category 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Missing 
 
 
 
 
 
 
 
 
Talazoparib 1 mg (N = xx) 
 
 
 
 
 
 
 
Grade 0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Missing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Total 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
The date of analysis data transfer is DDMONYYYY.  
Percentage is based on N. 
Toxicity grading is per NCI-CTCAE version 4.03. 
[1] Baseline is defined as the last non-missing value prior to the first dose. 
[2] Based on all test results collected in the treatment-emergent period. For each parameter, patients are counted once only at the worst grade. 
Data source:  Listing 16.2.8.2. 
 
Programming Specification: 
• 
Include all chemistry parameters specified in the protocol without CTC grades (where applicable), output one 
parameter for each file.   
• 
Post-baseline laboratory assessments include both scheduled and unscheduled visits. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 49 
 
Table 14.3.4.3: Hematology Shift Table Based on Normal Range (Safety Population) 
Baseline [1] 
Worst Post-baseline Value [2] 
Category 
Low 
Normal 
High 
Low and High 
Missing 
  
Talazoparib 1 mg (N = xx) 
 
 
 
 
 
 
   Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Missing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Total 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
Percentage is based on N.  
[1] Baseline is defined as the last non-missing value prior to the first dose. 
[2] The categories of Low and High are defined by normal ranges. If the patient has laboratory values that are both Low and High, then the 
patient will be counted in the category “Low and High”. Patients will be counted once only. 
Data source:  Listing 16.2.8.1. 
 
Programming Specification: 
• 
Include all hematology parameters specified in the protocol without CTC grades (where applicable), output one 
parameter for each file.   
• 
Parameters that have criteria available for both low and high values are summarized for both criteria (low and high).  
Patients will only be counted once for each criterion. The same patient can be counted for both criteria if the patient has 
laboratory values meeting each criterion (low and high).   
• 
Post-baseline laboratory assessments include both scheduled and unscheduled visits. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 50 
 
Table 14.3.4.4: Chemistry Shift Table Based on Normal Range (Safety Population) 
Baseline [1] 
Worst Post-baseline Value [2] 
Category 
Low 
Normal 
High 
Low and High 
Missing 
  
Talazoparib 1 mg (N = xx) 
 
 
 
 
 
 
   Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Missing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Total 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
Percentage is based on N.  
[1] Baseline is defined as the last non-missing value prior to the first dose. 
[2] The categories of Low and High are defined by normal ranges. If the patient has laboratory values that are both Low and High, then the patient 
will be counted in the category “Low and High”. Patients will be counted once only. 
Data source:  Listing 16.2.8.2. 
 
Programming Specification: 
• 
Include all chemistry parameters specified in the protocol without CTC grades (where applicable), output one parameter 
for each file.   
• 
Parameters that have criteria available for both low and high values are summarized for both criteria (low and high).  
Patients will only be counted once for each criterion. The same patient can be counted for both criteria if the patient has 
laboratory values meeting each criterion (low and high).   
• 
Post-baseline laboratory assessments include both scheduled and unscheduled visits. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
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Table 14.3.4.5: Change from Baseline Hematology Laboratory Result (Safety Population) 
Visit/Time Point 
   Statistics 
Talazoparib 
1 mg 
(N = xx) 
Lab Results 
Change from Baseline[2] 
Baseline [1] 
 
 
   n 
xxx 
 
   Mean (SD) 
xx.x (xx.x) 
 
   Median 
xx.x 
 
   Min, Max 
xx.x, xx.x 
 
  
 
 
Visit name 1 
 
 
   n 
xxx 
xxx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx.x, xx.x 
xx.x, xx.x 
The date of analysis data transfer is DDMONYYYY. 
SD: standard deviation, Min: minimum, Max: maximum, n: counts of non-missing values. 
[1] Baseline is defined as the last non-missing value prior to the first dose. 
[2] Only patients with a value at both baseline and during study treatment are included. 
Data source:  Listing 16.2.8.1. 
 
Programming Specification: 
• 
For each laboratory test, only patients with a value at both baseline and during study treatment are included. 
• 
Post-baseline laboratory assessments include only scheduled visits.   
• 
Output one parameter for each file. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 52 
 
Table 14.3.4.6: Change from Baseline Chemistry Laboratory Result (Safety Population) 
Visit/Time Point 
   Statistics 
Talazoparib 
1 mg 
(N = xx) 
Lab Results 
Change from Baseline[2] 
Baseline [1] 
 
 
   n 
xxx 
 
   Mean (SD) 
xx.x (xx.x) 
 
   Median 
xx.x 
 
   Min, Max 
xx.x, xx.x 
 
  
  
 
Visit name 1 
 
 
   n 
xxx 
xxx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx.x, xx.x 
xx.x, xx.x 
The date of analysis data transfer is DDMONYYYY. 
SD: standard deviation, Min: minimum, Max: maximum, n: counts of non-missing values. 
[1] Baseline is defined as the last non-missing value prior to the first dose. 
[2] Only patients with a value at both baseline and during study treatment are included. 
Data source:  Listing 16.2.8.2. 
 
Programming Specification: 
• 
For each laboratory test, only patients with a value at both baseline and during study treatment are included. 
• 
Post-baseline laboratory assessments include only scheduled visits. 
• 
Output one parameter for each file. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 53 
 
Table 14.3.4.7: Treatment-Emergent Liver Function Test Elevations (Safety Population) 
Test Criteria 
Talazoparib 
1 mg 
(N = xx) 
Number of Patients Who Met at Least One Criteria [1] 
xx (xx.x%) 
 
 
ALT >= 3xULN 
xx (xx.x%) 
AST >= 3xULN 
xx (xx.x%) 
ALT or AST >= 3xULN 
xx (xx.x%) 
ALT or AST > 5xULN 
xx (xx.x%) 
ALT or AST > 10xULN 
xx (xx.x%) 
ALT or AST > 20xULN 
xx (xx.x%) 
TBL > 2xULN 
xx (xx.x%) 
ALT or AST >= 3xULN and TBL > 2xULN 
xx (xx.x%) 
Concurrent ALT or AST >= 3xULN and TBL > 2xULN 
xx (xx.x%) 
ALT or AST >= 3xULN and TBL > 2xULN and ALP < 2xULN 
xx (xx.x%) 
Concurrent ALT or AST >= 3xULN and TBL > 2xULN and ALP < 2xULN [2] 
xx (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
ALT: alanine aminotransferase, AST: aspartate aminotransferase, ALP: alkaline phosphatase, TBL: total bilirubin, ULN: upper limit of normal. 
Percentage is based on N. 
[1] Criteria are based on worst postbaseline value for any specific parameter. Criteria with multiple parameters are based on worst postbaseline 
value for each parameter taken at any visit except that concurrent measurements are those occurring on the same date. 
[2] Hy’s Law according to FDA Guidance for Industry - Drug-Induced Liver Injury:  Premarketing Clinical Evaluation (2009). 
Data source:  Listing 16.2.8.2. 
 
Programming Specification: 
• 
Only count the number of patients who satisfied the criteria. If count=0 for “ALT or AST >= 3xULN”, more 
stringent criteria (eg, “ALT or AST > 5xULN”) is not shown. 
• 
Post-baseline laboratory assessments include both scheduled and unscheduled visits.   
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 54 
 
Table 14.3.5.1: Change from Baseline Vital Sign Results (Safety Population) 
Visit/Time Point 
   Statistics 
Talazoparib 
1 mg 
(N = xx) 
Vital Sign Results 
Change from Baseline[2] 
Baseline [1] 
 
 
   n 
xxx 
 
   Mean (SD) 
xx.x (xx.x) 
 
   Median 
xx.x 
 
   Min, Max 
xx.x, xx.x 
 
  
 
 
Visit name 1 
 
 
   n 
xxx 
xxx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx.x, xx.x 
xx.x, xx.x 
The date of analysis data transfer is DDMONYYYY. 
SD: standard deviation, Min: minimum, Max: maximum, n: counts of non-missing values. 
[1] Baseline is defined as the last non-missing value prior to the first dose. 
[2] Only patients with a value at both baseline and during study treatment are included. 
Data source:  Listing 16.2.8.3. 
 
Programming Specification: 
• 
For each parameter, only patients with a value at both baseline and during study treatment are included. 
• 
Vital sign parameters include blood pressure (systolic/diastolic,), heart rate, respiratory rate, and body temperature. 
• 
Post-baseline assessments include only scheduled visits. 
• 
Output one parameter for each file. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 55 
 
Table 14.3.5.2: Clinically Notable Changes in Vital Sign Results (Safety Population) 
Parameter [unit] 
   Category 
Talazoparib 
1 mg 
(N = xx) 
Number of Patients Who Met at Least One Criteria 
xx (xx.x%) 
 
 
Systolic Blood Pressure [mmHg] <-total> 
xx (xx.x%) 
   High Only (≥155 with Increase from Baseline of ≥30) 
xx (xx.x%) 
   Low Only (≤90 with Decrease from Baseline of ≥20) 
xx (xx.x%) 
   Both High and Low 
xx (xx.x%) 
 
 
Diastolic Blood Pressure [mmHg] <-total> 
xx (xx.x%) 
   High Only (≥100 with Increase from Baseline of ≥15) 
xx (xx.x%) 
   Low Only (≤50 with Decrease from Baseline of ≥15) 
xx (xx.x%) 
   Both High and Low 
xx (xx.x%) 
 
 
Heart rate [bpm] <-total> 
xx (xx.x%) 
   High Only (≥100 with Increase from Baseline of ≥30) 
xx (xx.x%) 
   Low Only (≤50 with Decrease from Baseline of ≥15) 
xx (xx.x%) 
   Both High and Low 
xx (xx.x%) 
 
 
Respiratory Rate [bpm] <-total> 
xx (xx.x%) 
   High Only (≥25) 
xx (xx.x%) 
   Low Only (<10) 
xx (xx.x%) 
   Both High and Low 
xx (xx.x%) 
 
 
Oral Body Temperature [°C] <-total> 
xx (xx.x%) 
   High Only (>39) 
xx (xx.x%) 
   Low Only (≤ 35) 
xx (xx.x%) 
   Both High and Low 
xx (xx.x%) 
The date of analysis data transfer is DDMONYYYY. 
Baseline is defined as the last non-missing value prior to the first dose. 
mmHg: millimeters of mercury, bpm: beats per minute. 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 56 
 
Parameter [unit] 
   Category 
Talazoparib 
1 mg 
(N = xx) 
If a patient has both High and Low post baseline values then count in High and Low. 
A patient with multiple occurrences for a given abnormality category is counted only once. 
Percentage is based on N. 
Data source:  Listing 16.2.8.3. 
 
Programming Specification: 
• 
Only count the number of patients who satisfied the criteria. If count=0 for “High/Low only”, criteria “Both High and 
Low” is not shown  
• 
If no abnormality for a given category, display only parameter [unit] <-total> row.   
• 
Post-baseline assessments include both scheduled and unscheduled visits. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 57 
 
Table 14.3.6: Change from Baseline ECG Results (Safety Population) 
Visit/Time Point 
   Statistics 
Talazoparib 
1 mg 
(N = xx) 
ECG Results 
Change from Baseline 
Screening / Baseline [1] 
 
 
   n 
xxx 
 
   Mean (SD) 
xx.x (xx.x) 
 
   Median 
xx.x 
 
   Min, Max 
xx.x, xx.x 
 
  
 
 
Safety Follow-up 
 
 
   n 
xxx 
xxx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx.x, xx.x 
xx.x, xx.x 
The date of analysis data transfer is DDMONYYYY. 
SD: standard deviation, Min: minimum, Max: maximum, n: counts of non-missing values. 
[1] Baseline is the measurement at screening visit. 
Data source:  Listing 16.2.8.4.1. 
 
Programming Specification: 
• 
For each parameter, only patients with a value at both screening and Safety follow-up are included.   
• 
ECG parameters include QT, QTcF, QTcB, HR, PR, and QRS.   
• 
Post-baseline assessments include only scheduled visits.    
• 
Output one parameter for each file. 
 


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Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 61 
 
Table 14.4.1.5: Overall Summary of Plasma Talazoparib PK Parameters (PK Analysis Population) 
Parameter (unit) 
   Statistics 
Day 1 
Day 22 
 
 
 
   n 
xx 
xx 
   Cmax (ng/mL) 
xx.x ± x.xx (xx.x) 
xx.x ± x.xx (xx.x) 
   tmax (h) 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
   AUC24h (h*ng/mL) 
xx.x ± x.xx (xx.x) 
xx.x ± x.xx (xx.x) 
   CL/F (L/h) 
xx.x ± x.xx (xx.x) 
xx.x ± x.xx (xx.x) 
   RAUC 
x.xx ± x.xxx (xx.x) 
x.xx ± x.xxx (xx.x) 
 
 
 
The date of analysis data transfer is DDMONYYYY. 
SD: standard deviation, CV%: coefficient of variation (%), n: number of non-missing values. 
Statistics are reported as the arithmetic mean ± SD (%CV) with the following exception: for tmax, the median (min, max) is reported. 
Data source: Table 14.4.1.3 and Table 14.4.1.4. 
 


Protocol MDV3800-14  Tables, Listings, and Figures Specifications 
 
 
Page 62 
 
Appendix 2.2. Section 14 Figures 
Figure 14.4.1.3: Mean (SD) Plasma Talazoparib Concentration-Time Profiles (PK Population) 
 
Day x 
 
The date of analysis data transfer is DDMONYYYY. 
Predose concentrations below the lower limit of quantitation ( BLQ) values (< 25.0 pg/mL) are set as zero in the linear scale plot 
and set as missing in the semi-logarithmic scale plot. 
SD: standard deviation. 
Data source:  Table 14.4.1.2. 
 
Programming Specification: 
• 
Plot Separately for Day 1 and Day 22. 
• 
Y-axis label: Plasma Concentration (pg/mL). 


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