Antineoplastic Agents

All Drugs and Chemicals

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Pfizer Pfizer CT.gov Call Center

This is a trial to investigate the pharmacokinetics (PK) and the safety of talazoparib in patients with advanced solid tumors and impaired hepatic function.

At the end of the study, patients with no clinically significant toxicities, no contraindications to continue treatment with talazoparib, and no disease progression (underlying cancer progression) may be eligible to continue talazoparib treatment in a separate open-label extension study. The decision to allow the patient to continue dosing with talazoparib in an open-label extension (OLE) study will be based on potential overall benefit-risk and patient meeting eligibility criteria for OLE.

An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800)

A PHASE I OPEN-LABEL PHARMACOKINETICS AND SAFETY STUDY OF TALAZOPARIB (MDV3800) IN PATIENTS WITH ADVANCED SOLID TUMORS AND NORMAL OR VARYING DEGREES OF HEPATIC IMPAIRMENT

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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. TEAEs were events between first dose of Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs.

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 Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs leading to study drug discontinuation are reported.

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 Talazoparib and up to 30 days after the last dose of Talazoparib (up to 52 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Number of participants with TEAEs resulting in death are reported.

A treatment-related adverse event was any untoward medical occurrence attributed to talazoparib in a participant who received talazoparib. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; Congenital anomaly. Relatedness to talazoparib was assessed by the investigator.

AUC0-24 of talazoparib was defined as the area under the free plasma 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 free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu\*AUC0-24. fu= Fraction of Unbound (fu) Plasma.

Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu\*Cmax.

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 and reported as percentage (%).

AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu\*AUC0-24.

Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu\*Cmax

Ctrough was defined as plasma trough (pre-dose) concentration of talazoparib. Acceptance criteria for Ctrough on Day 15 and Day 22: received 10 consecutive days of dosing immediately before PK sampling day; Sample drawn within 24 +/-2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day. Ctrough on Day 8: received 7 consecutive days of dosing immediately before PK sampling day; sample drawn within 24 +/- 2 hours of the previous dose, and not more than +10 minute after the drug administration on the PK collection day.

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.

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

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

Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose.

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

Ae 0-24% was defined as the amount of talazoparib 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 post dose (AUC0-24).

Clinically significant laboratory abnormalities included aspartate transaminase (AST) or alanine aminotransferase (ALT) \>=3 times ULN (\>5 \*ULN if baseline ALT/AST is \>3 \*ULN) and total bilirubin (TBL) \>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/microliter).

Systolic blood pressure and diastolic blood pressure were evaluated for examination of vital signs.

Heart rate was measured in beats per minute.

Respiratory rate was measured in terms of breaths per minute.

Pre-specified 12-Lead electrocardiogram (ECG) Criteria: QTCF (Fridericia's correction formula) : \>=450 to \<480 milliseconds, \>=480 to \<500 milliseconds, \>=500 milliseconds, increase from baseline \>=30 - \<60, increase from baseline \>=60, PR interval: \>=300 milliseconds, increase from baseline \>=25%; QRS duration: \>=140 milliseconds, increase from baseline \>=50%; QT interval: \>=500 milliseconds; QT Interval: \>= 500 milliseconds.

As per ECOG, participant's performance status was measured as: 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.

Medivation, Inc.

Pfizer

Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.

Participants with TB and AST \<=ULN received 0.5 mg (2 capsules of 0.25 mg) of talazoparib daily, orally for 22 days.

Talazoparib: Normal Hepatic Function

Participants with TB \<=ULN and AST greater than (\>) ULN or TB \>1.0 to 1.5\* ULN and any AST value, received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.

Talazoparib: Mild Hepatic Impairment

Participants with TB \>1.5 to 3.0 \*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.

Talazoparib: Moderate Hepatic Impairment

Participants with TB \>3\*ULN and any AST value received talazoparib 0.5 mg (2 capsules of 0.25 mg), orally once daily for 22 days.

Talazoparib: Severe Hepatic Impairment

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Safety analysis set included all participants who received any amount of talazoparib.

Pfizer ClinicalTrials.gov Call Center

AUC0-24 was natural log-transformed and analyzed using an analysis of variance (ANOVA) model with hepatic function group as a fixed effect.

Pharmacokinetic (PK) evaluable analysis population included all enrolled participants who completed Day 22 visit, missed less than 5 consecutive doses, received at least 10 consecutive days of 0.5 mg talazoparib daily dose immediately preceding Day 22 visit without dose interruption, not vomited talazoparib dose on Day 1 and last day of dose, at least 85% of total plasma PK samples collection was reported and provided at least 1 of talazoparib PK parameters of primary interest from Day 22 visit.

Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22

Cmax was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.

PK evaluable analysis population included all enrolled participants who completed Day 22 visit, missed less than 5 consecutive doses, received at least 10 consecutive days of 0.5 mg talazoparib daily dose immediately preceding Day 22 visit without dose interruption, not vomited talazoparib dose on Day 1 and last day of dose, at least 85% of total plasma PK samples collection was reported and provided at least 1 of talazoparib PK parameters of primary interest from Day 22 visit.

Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22

AUC0-24u was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.

Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22

Cmaxu was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.

Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22

AUC0-24 was natural log-transformed and analyzed using an ANOVA model with hepatic function group as a fixed effect.

PK parameter analysis population included all enrolled participants who received at least 1 dose of talazoparib and had at least 1 of the talazoparib PK parameters. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1

Cmax was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.

Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1

Fraction of Unbound (fu) Plasma Talazoparib on Day 1

AUC0-24u was natural log-transformed and analyzed using ANOVA model with hepatic function group as a fixed effect.

Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1

Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1

Day 8

Day 15

Day 22

Analysis population for this outcome measure included those participants who met acceptance criteria for Ctrough. Here 'number analyzed' signifies number of participants evaluable for each specified row.

Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22

Analysis population included participants with available data.

Fraction of Unbound (fu) Plasma Talazoparib on Day 22

PK evaluable analysis population was analyzed. Here, "Overall Number of Participants Analyzed" =participants evaluable for this outcome measure.

Accumulation Ratio (Rac) of Plasma Talazoparib

Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22

Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22

Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1

Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1

Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22

Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22

Renal Clearance (CLr) of Talazoparib on Day 22

TEAEs

SAEs

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Number of Participants With TEAEs Leading to Study Drug Discontinuation

Number of Participants With TEAEs Resulting in Death

Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs

Number of Participants With Clinically Significant Laboratory Abnormalities

Systolic Blood Pressure: Baseline

Systolic Blood Pressure: Change at Day 2

Systolic Blood Pressure: Change at Day 8

Systolic Blood Pressure: Change at Day 15

Systolic Blood Pressure: Change at Day 22

Systolic Blood Pressure: Change at end of study (Day 52)

Diastolic Blood Pressure: Baseline

Diastolic Blood Pressure: Change at Day 2

Diastolic Blood Pressure: Change at Day 8

Diastolic Blood Pressure: Change at Day 15

Diastolic Blood Pressure: Change at Day 22

Diastolic Blood Pressure: Change at end of study (Day 52)

Safety analysis set included all participants who received any amount of talazoparib. Here, 'number analyzed' signifies participants evaluable for each specified row.

Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study

Baseline

Change at Day 2

Change at Day 8

Change at Day 15

Change at Day 22

Change at end of study (Day 52)

Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study

Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study

Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study

QTCF: >=450 - <480 milliseconds

QTCF: >=480 - <500 milliseconds

QTCF: >=500 milliseconds

QTCF: Increase from baseline >=30 - <60 milliseconds

QTCF: Increase from baseline >=60 milliseconds

PR Interval: >=300 milliseconds

PR Interval: Increase from baseline >=25%

QRS Duration: >=140 milliseconds

QRS Duration: Increase from baseline >=50%

QT Interval: >=500 milliseconds

Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria

Screening

Day -1

Safety follow up

Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status

Participants with total bilirubin (TB) and aspartate aminotransferase (AST) less than or equal to (\<=) upper limit of normal (ULN), received talazoparib 0.5 milligram (mg) (2 capsules of 0.25 mg), orally once daily for 22 days.

Spots Global Cancer Trial Database for An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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