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

A Phase 1 study testing Talazoparib in people with Advanced Solid Tumors, run by Pfizer at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumors
What is being tested?: Talazoparib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 38 participants
Where: 11 sitesUnited States
Study dates: 30 Sep 2016to 12 Feb 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Signed and dated Informed Consent Form (by the patient or a legally acceptable representative as per the local regulations).
Female or male at least 18 years of age.
Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator
Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
Expected life expectancy of ≥ 3 months.
Able to swallow the study drug (no contraindication to oral agents).

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Hepatic function at screening and enrollment as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria.
Adequate other organ function at screening and enrollment.
Female patients of childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception from the time of the first dose of study drug through 7 months after the last dose of study drug.
Male patients must agree to use a condom when having sex with a pregnant woman or with a non-pregnant female partner of childbearing potential, from 21 days before the first dose of study drug through 4 months after last dose of study drug.
Female patients must not be breastfeeding at screening nor during the study participation until 7 months after the last dose of the study drug.
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Who cannot join

Treatment within 14 days or five half lives prior to enrollment whichever is longer with any type of systemic anticancer-therapy or any investigational drug
Have not recovered (recovery is defined as CTCAE grade ≤ 1) from the acute toxicities of previous anticancer standard or investigational therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
Major surgery within 28 days prior to enrollment.
Serious accompanying cardiac disorder
Active known or suspected brain metastasis or active leptomeningeal disease needing treatment
Symptomatic or impending spinal cord compression or cauda equine syndrome

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Has undergone a liver transplant, kidney transplant or nephrectomy.
Prior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor.
Known myelodysplastic syndrome
Seropositive for human immunodeficiency virus (HIV).
Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
Gastrointestinal disorder affecting absorption.
Known or suspected hypersensitivity to any of the talazoparib capsule components.
Any condition or reason that interferes with ability to participate in the study, tolerate treatment or assessments associated with the protocol, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Medical Monitor

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

United States11 sites

UCLA Hematology/Oncology - Alhambra
Alhambra, California, 91801
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
Bakersfield, California, 93309
St. Joseph Heritage Healthcare
Fullerton, California, 92835
St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
Fullerton, California, 92835
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
UCLA Hematology/Oncology
Los Angeles, California, 90095
Orlando Health, Inc.
Orlando, Florida, 32806
UCLA Hematology/Oncology - Porter Ranch
Porter Ranch, California, 91326
UCLA Hematology/Oncology - Santa Monica
Santa Monica, California, 90404
UCLA Torrance Oncology
Torrance, California, 90505
UCLA Hematology/Oncology - Santa Clarita
Valencia, California, 91355

Other trials in United States

About this study

Official title: 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

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

Read the detailed description

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.

Conditions: Advanced Solid Tumors
Being tested: Talazoparib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TalazoparibDrug
Also called MDV3800, BMN673
Daily oral doses of talazoparib 0.5 mg

Study groups in NCT02997176
Study group	Role	What they receive
Group A (control, normal hepatic function)	Experimental	Not described Receives: Drug: Talazoparib
Group B (mild hepatic dysfunction)	Experimental	Not described Receives: Drug: Talazoparib
Group C (moderate hepatic dysfunction)	Experimental	Not described Receives: Drug: Talazoparib
Group D (severe hepatic dysfunction)	Experimental	Not described Receives: Drug: Talazoparib

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
Measured: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22
Cmax was defined as the maximum observed plasma concentration of talazoparib.
Measured: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22
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.
Measured: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu*Cmax.
Measured: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22

Secondary outcomes (24)

Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
Measured: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1
Cmax was defined as the maximum observed plasma concentration of talazoparib.
Measured: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
Measured: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Fraction of Unbound (fu) Plasma Talazoparib on Day 1
Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%).
Measured: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1
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.
Measured: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu*Cmax
Measured: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22
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.
Measured: Pre-dose on Day 8, 15 and 22
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
Measured: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Fraction of Unbound (fu) Plasma Talazoparib on Day 22
Fraction of unbound drug (fu) was defined as the ratio of unbound drug concentration to the total drug concentration and reported as percentage (%).
Measured: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Accumulation Ratio (Rac) of Plasma Talazoparib
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.
Measured: Pre-dose (within 60 minutes prior to dose) on Day 1, pre-dose(24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose) on Day 22 and 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Days 1 and 22
Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22
Talazoparib clearance is a measure of the rate at which talazoparib is metabolized or eliminated by normal biological processes.
Measured: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22
Clearance of unbound talazoparib is a measure of the rate at which unbound talazoparib is metabolized or eliminated by normal biological processes.
Measured: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1
Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose.
Measured: A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1
Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1
Ae0-24% was defined as the amount of talazoparib excreted in urine from time 0 to 24 hours expressed as percentage of administered dose.
Measured: A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22
Ae 0-24 is the amount of talazoparib excreted unchanged in urine from time 0 to 24 hours post dose.
Measured: Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 22
Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22
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.
Measured: Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours (hrs) on Day 22
Renal Clearance (CLr) of Talazoparib on Day 22
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).
Measured: Ae: Post-dose at any time between 0 to 12, 12 to 24 hrs on Day 22; AUC0-24: Pre-dose (24 hrs +/- 60 minutes from previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, any time between 8 to12, 24 hrs post-dose on Day 22
Number of Participants With Clinically Significant Laboratory Abnormalities
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).
Measured: Baseline up to 30 days after last dose of study drug (up to 52 days)
Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study
Systolic blood pressure and diastolic blood pressure were evaluated for examination of vital signs.
Measured: Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study
Heart rate was measured in beats per minute.
Measured: Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study
Respiratory rate was measured in terms of breaths per minute.
Measured: Baseline, Day 8, 15, 22 and End of Study (Day 52)
Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study
Measured: Baseline, Day 8, 15, 22 and End of Study (Day 52)
Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria
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.
Measured: Baseline up to 30 days after last dose of study drug (up to 52 days)
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
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.
Measured: Screening (2 to 28 days prior to Day 1), Day -1 (1 day prior to Day 1), safety follow up (Visit up to Day 52)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Sep 201612 Feb 2020

First posted19 Dec 2016 (estimated)
Study start30 Sep 2016
Primary completion12 Feb 2020
Study completion12 Feb 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02997176
Sponsor's protocol ID: MDV3800-02
Other IDs: C3441002
Status last verified: Feb 2021
First submitted: 15 Dec 2016
Last updated: 25 Feb 2021
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: No: 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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Advanced Solid Tumors trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02997176
Acronym / sponsor ID: MDV3800-02
Conditions: Advanced Solid Tumors
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 38 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Collaborators: Medivation, Inc.
Study start: 30 Sep 2016 (actual)
Primary completion: 12 Feb 2020 (actual)
Study completion: 12 Feb 2020 (actual)
First posted: 19 Dec 2016 (estimated)
Results: Posted 25 Feb 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Group A (control, normal hepatic function)	Experimental	Drug: Talazoparib
Group B (mild hepatic dysfunction)	Experimental	Drug: Talazoparib
Group C (moderate hepatic dysfunction)	Experimental	Drug: Talazoparib
Group D (severe hepatic dysfunction)	Experimental	Drug: Talazoparib

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Signed and dated Informed Consent Form (by the patient or a legally acceptable representative as per the local regulations).
Female or male at least 18 years of age.
Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator
Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
Expected life expectancy of ≥ 3 months.

Key exclusion criteria (14 listed)

Treatment within 14 days or five half lives prior to enrollment whichever is longer with any type of systemic anticancer-therapy or any investigational drug
Have not recovered (recovery is defined as CTCAE grade ≤ 1) from the acute toxicities of previous anticancer standard or investigational therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
Major surgery within 28 days prior to enrollment.
Serious accompanying cardiac disorder
Active known or suspected brain metastasis or active leptomeningeal disease needing treatment

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TalazoparibAlso: MDV3800, BMN673Daily oral doses of talazoparib 0.5 mg	Drug	Group A (control, normal hepatic function), Group B (mild hepatic dysfunction), Group C (moderate hepatic dysfunction), Group D (severe hepatic dysfunction)

Primary outcome

Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Cmax was defined as the maximum observed plasma concentration of talazoparib.
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
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.
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu*Cmax.

24 secondary outcomes

Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Fraction of Unbound (fu) Plasma Talazoparib on Day 1
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1
Time frame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22
Time frame: Pre-dose on Day 8, 15 and 22
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Fraction of Unbound (fu) Plasma Talazoparib on Day 22
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Accumulation Ratio (Rac) of Plasma Talazoparib
Time frame: Pre-dose (within 60 minutes prior to dose) on Day 1, pre-dose(24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose) on Day 22 and 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Days 1 and 22
Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22
Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1
Time frame: A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1
Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1
Time frame: A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1
Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22
Time frame: Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 22
Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22
Time frame: Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours (hrs) on Day 22
Renal Clearance (CLr) of Talazoparib on Day 22
Time frame: Ae: Post-dose at any time between 0 to 12, 12 to 24 hrs on Day 22; AUC0-24: Pre-dose (24 hrs +/- 60 minutes from previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, any time between 8 to12, 24 hrs post-dose on Day 22
Number of Participants With Clinically Significant Laboratory Abnormalities
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study
Time frame: Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study
Time frame: Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study
Time frame: Baseline, Day 8, 15, 22 and End of Study (Day 52)
Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study
Time frame: Baseline, Day 8, 15, 22 and End of Study (Day 52)
Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria
Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
Time frame: Screening (2 to 28 days prior to Day 1), Day -1 (1 day prior to Day 1), safety follow up (Visit up to Day 52)

Results and safety

Results posted to the registry on 25 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Talazoparib: Normal Hepatic Function	7	6
Talazoparib: Mild Hepatic Impairment	10	8
Talazoparib: Moderate Hepatic Impairment	5	3
Talazoparib: Severe Hepatic Impairment	16	5

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

Time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram*hour per milliliter

Measure	Talazoparib: Normal Hepatic Function n = 6	Talazoparib: Mild Hepatic Impairment n = 6	Talazoparib: Moderate Hepatic Impairment n = 3	Talazoparib: Severe Hepatic Impairment n = 2
Value	111.8 (30)	159.0 (99)	123.6 (30)	NA (NA)

Talazoparib: Normal Hepatic Function vs Talazoparib: Mild Hepatic Impairment: Percent Ratio of Geometric Means: 142.19 (90% CI 79.92 to 252.98)
Talazoparib: Normal Hepatic Function vs Talazoparib: Moderate Hepatic Impairment: Percent Ratio of Geometric Means: 110.54 (90% CI 54.58 to 223.85)

Population analysed: 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.

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

Measure	Talazoparib: Normal Hepatic Function n = 6	Talazoparib: Mild Hepatic Impairment n = 6	Talazoparib: Moderate Hepatic Impairment n = 3	Talazoparib: Severe Hepatic Impairment n = 2
Value	10.30 (23)	11.30 (65)	13.56 (23)	NA (NA)

Talazoparib: Normal Hepatic Function vs Talazoparib: Mild Hepatic Impairment: Percent Ratio of Geometric Means: 109.76 (90% CI 70.93 to 169.84)
Talazoparib: Normal Hepatic Function vs Talazoparib: Moderate Hepatic Impairment: Percent Ratio of Geometric Means: 131.67 (90% CI 77.14 to 224.74)

Population analysed: 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.

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

Measure	Talazoparib: Normal Hepatic Function n = 6	Talazoparib: Mild Hepatic Impairment n = 6	Talazoparib: Moderate Hepatic Impairment n = 3	Talazoparib: Severe Hepatic Impairment n = 2
Value	30.17 (11)	45.08 (84)	33.50 (35)	NA (NA)

Talazoparib: Normal Hepatic Function vs Talazoparib: Mild Hepatic Impairment: Percent Ratio of Geometric Means: 149.39 (90% CI 91.49 to 243.93)
Talazoparib: Normal Hepatic Function vs Talazoparib: Moderate Hepatic Impairment: Percent Ratio of Geometric Means: 111.04 (90% CI 60.91 to 202.43)

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

Measure	Talazoparib: Normal Hepatic Function n = 6	Talazoparib: Mild Hepatic Impairment n = 6	Talazoparib: Moderate Hepatic Impairment n = 3	Talazoparib: Severe Hepatic Impairment n = 2
Value	2.778 (27)	3.204 (56)	3.675 (28)	NA (NA)

Talazoparib: Normal Hepatic Function vs Talazoparib: Mild Hepatic Impairment: Percent Ratio of Geometric Means: 115.32 (90% CI 77.95 to 170.6)
Talazoparib: Normal Hepatic Function vs Talazoparib: Moderate Hepatic Impairment: Percent Ratio of Geometric Means: 132.26 (90% CI 81.87 to 213.67)

24 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to 30 days after last dose of study drug (up to 52 days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Talazoparib: Normal Hepatic Function	1 of 7 (14.3%)	6 of 7 (85.7%)	0 of 7
Talazoparib: Mild Hepatic Impairment	3 of 10 (30%)	7 of 10 (70%)	0 of 10
Talazoparib: Moderate Hepatic Impairment	2 of 5 (40%)	3 of 5 (60%)	1 of 5
Talazoparib: Severe Hepatic Impairment	13 of 16 (81.3%)	10 of 16 (62.5%)	7 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer Pfizer CT.gov Call Center study director

Pfizer

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Talazoparib in people with Advanced Solid Tumors, run by Pfizer at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22 (time frame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02997176.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2021.