An Open-Label Pharmacokinetics and Safety Study of Talazoparib

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Renal clearance was calculated as cumulative amount of drug excreted in urine during the 24 hours dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to 24 hours postdose.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of investigational product and up to 30 days after the last dose of investigational product (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.

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

Heart rate was measured in terms of beats per minute.

Respiratory rate was measured in terms of breaths per minute.

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

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

As per ECOG, participant's performance status was measured on 5 point scale: 0=fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature, e.g., light housework, office work. 2= ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5: dead.