Advanced Solid TumorsPhase 1NCT03077607

A Study to Evaluate the Effect of Itraconazole and Rifampin on the Pharmacokinetics of Talazoparib in Patients With Advanced Solid Tumors

A Phase 1 study testing Talazoparib, Itraconazole and Rifampin in people with Advanced Solid Tumors, run by Pfizer at 7 sites in 4 countries.

Completed

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

Official record

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Trial summary

This is a study in patients with advanced solid tumors for the investigation of P-gp inhibition and induction on the PK of talazoparib. 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, Itraconazole and Rifampin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 7 sitesin 4 countries
Study dates: 7 Nov 2016to 20 Jan 2018
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

Arm A: At least 18 years of age and <65 years of age (at the time point of consent) and willing and able to provide informed consent. Arm B: At least 18 years of age (at the time point of consent) and willing and able to provide informed consent.
Histologically confirmed advanced solid tumor (limited to platinum-resistant ovarian carcinoma, cervical adenocarcinoma, small cell lung carcinoma or triple-negative breast cancer) judged by the Investigator to not be appropriate for standard therapy.
ECOG performance status ≤ 2 at screening and at time of enrollment.
Expected life expectancy of ≥ 3 months.
Able to swallow the study drug and comply with study requirements.
Female subjects may be enrolled if they are considered not of childbearing potential, or who are post-menopausal, or are of childbearing potential using a highly effective form of contraceptive, and female subjects should not donate eggs from the time point of investigational medicinal product (IMP) administration until at least 45 days thereafter.

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Males with partners of childbearing potential may be enrolled if they use a condom when having sex with a pregnant woman or with a woman of childbearing potential, and do not donate sperm from the time point of study drug administration until at least 105 days thereafter, and males should not donate sperm from the time point of study drug administration until at least 105 days thereafter.
Female subjects must not be breastfeeding at screening and during the study participation until 45 days 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 5 half lives prior to dosing with any type of systemic anticancer therapy or any investigational agent, whichever is longer
Major surgery within 8 weeks before screening.
Serious accompanying disorder or impaired organ function.
Symptomatic or impending spinal cord compression or cauda equina syndrome.
Non-healing wound, ulcer, or bone fracture, not including a pathological bone fracture caused by a pre-existent pathological bone lesion.
Known myelodysplastic syndrome.

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Subjects with the following serologies should be excluded: HBsAg+ or anti-HBc+;HCV+; HIV+.
Serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
Gastrointestinal disorder affecting absorption.
Known hypersensitivity to any of the talazoparib capsule components.
Any condition or reason 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 Sponsor (e.g. non-compliance, excessive alcohol consumption, intake of drugs of abuse unless these drugs are medically indicated [e.g. opiates for pain relief].

Trial locations and contacts

7 sites in 4 countries.

Country

City, postcode or hospital

7 sites in 4 countries

Russia4 sites

I.M. Sechenov First Moscow State Medical University
Moscow, 119435
I.M. Sechenov First Moscow State Medical University
Moscow, 119991
"BioEq" LLC
Saint Petersburg, 197342
State budget healthcare institution of Yaroslavl region "Regional clinical oncology hospital"
Yaroslavl, 150054

Other trials in Russia

Hungary1 site

PRA Magyarorszag Kft, Fazis I-es Klinikai Farmakologiai Vizsgalohely
Budapest, 1077

Other trials in Hungary

Moldova1 site

ARENSIA Exploratory Medicine Phase I Unit, PMSI Institute of Oncology
Chisinau, MD2025

Other trials in Moldova

Poland1 site

Szpital LUX MED
Warsaw, 02-801

Other trials in Poland

About this study

Official title: A PHASE 1 OPEN-LABEL, TWO-ARM,DRUG-DRUG INTERACTION STUDY TO EVALUATE THE EFFECT OF ITRACONAZOLE AND RIFAMPIN ON THE PHARMACOKINETICS OF TALAZOPARIB IN PATIENTS WITH ADVANCED SOLID TUMORS

This is a study in patients with advanced solid tumors for the investigation of P-gp inhibition and induction on the PK of talazoparib.

Read the detailed description

Subjects participating in this study with no clinically significant toxicities and no disease progression may be eligible to continue treatment on a separate extension protocol (MDV3800-13).

Conditions: Advanced Solid Tumors
Being tested: Talazoparib, Itraconazole, Rifampin

What participants receive

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

TalazoparibDrug
Arm A: 0.5 mg oral dose Arm B: 1 mg oral dose
ItraconazoleDrug
100 mg oral dose
RifampinDrug
600 mg oral dose

Study groups in NCT03077607
Study group	Role	What they receive
Arm A	Experimental	Subjects will receive a 0.5 mg talazoparib and 100 mg itraconazole. Receives: Drug: Talazoparib; Drug: Itraconazole
Arm B	Experimental	Subjects will receive 1 mg talazoparib and 600 mg rifampin. Receives: Drug: Talazoparib; Drug: Rifampin

What is being measured

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

Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole
T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Measured: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Itraconazole
T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Measured: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Talazoparib: Alone and in Combination With Itraconazole
T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Measured: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Rifampin
T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".
Measured: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Rifampin
T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".
Measured: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Talazoparib: Alone and in Combination With Rifampin
T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".
Measured: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25

Secondary outcomes (13)

Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Itraconazole
T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Measured: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Itraconazole
Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half. T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Measured: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Itraconazole
Clearance of talazoparib was measure of the rate at which it was metabolized or eliminated by normal biological processes. T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Measured: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Itraconazole
Apparent volume of distribution was defined as the theoretical volume in which the total amount of talazoparib would need to be uniformly distributed to produce its desired plasma concentration. T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Measured: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Rifampin
T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".
Measured: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Rifampin
Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half. T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".
Measured: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Rifampin
Apparent volume of distribution was defined as the theoretical volume in which the total amount of talazoparib would need to be uniformly distributed to produce its desired plasma concentration. T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".
Measured: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Rifampin
Clearance of talazoparib was measure of the rate at which it was metabolized or eliminated by normal biological processes. T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".
Measured: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An 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 or incapacity, congenital anomaly. A TEAE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pre-treatment state. AEs included both serious and non-serious adverse events.
Measured: Baseline up to end of study (up to 61 days)
Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters
Chemistry:(sodium135-146,potassium3.5-5.5,chloride95-109,glucose3.3-5.5,urea2.8-7.2,calcium2.2-2.65,phosphate0.8-1.45,triglyceride0.4-1.7,cholesterol2.6-5.2)millimoles/L, (bilirubin[direct0-3,total2-21],creatinine53- 110)micromole/L, (albumin35-52,protein65-83)g/L,(alkaline phosphatase30-120, aspartate amino[A]transferase[T]4-46, alanine AT4-49, lactic acid dehydrogenase200-460, gammaglutamylT7-50,creatinine kinase24-170)U/L. Hematology: hemoglobin(Hb)120-177, hematocrit0.35-0.49L/L, RBC4-5.9T/L, (platelet150- 400,WBC4-10,basophil<0.10,eosinophil<0.40, neutrophil1.50-7.00,monocyte<1.20,lymphocyte1.0 -3.70)G/L. Urine:(glucose,protein,ketone,Hb:negative/positive), specific gravity1.010-1.030g/cm^3, pH4.8-7.8, pale yellow-deep amber, microscopy[WBC0-5,leukocyte0-5,Hb0-3,cast0-1,bacteria0-500,epithelial0-6])Pcs/area. Coagulation:(activated partial thromboplastine time25-43,prothrombin time13.7-15.6) seconds,international normalized ratio0.89-1.1. Investigator judged clinical significance.
Measured: Baseline up to end of study (up to 61 days)
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Vital sign abnormalities: a) systolic blood pressure (SBP): 1) minimum less than (<) 90 millimeter of mercury (mmHg), 2) change from baseline maximum decrease greater than equal to (>=) 30 mmHg, 3) change from baseline maximum increase >=30 mmHg; b) diastolic blood pressure (DBP): 1) minimum <50 mmHg, 2) change from baseline maximum decrease >=20 mmHg, 3) change from baseline maximum increase >=20 mmHg; c) supine pulse rate: 1) minimum <40 beats per minute (bpm), 2) maximum >120 bpm; d) standing pulse rate: 1) minimum <40 bpm and 2) maximum >140 bpm. Clinical significance of vital signs abnormalities was judged by investigator.
Measured: Baseline up to end of study (up to 61 days)
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
ECG abnormalities: a) QT Interval: new absolute values greater than (>) 450, >480, >500 milliseconds (msec), increase from baseline >30 and >60 msec, b) QT interval using Fridericia's correction (QTcF) Interval: new absolute values >450, >480, >500 msec, increase from baseline >30 and > 60 msec, c) Heart rate: increase from baseline >25 percentage (%) and to a value >100 bpm, decrease from baseline >25% and to a value <50 bpm, d) PR Interval: increase from baseline > 25% and to a value >200 msec, e) QRS duration: increase from baseline > 25% and to a value >100 msec. Clinical significance of ECG abnormalities was judged by investigator.
Measured: Baseline up to end of study (up to 61 days)
Number of Participants With Clinically Significant Physical Examination Findings
Physical examination included examination of abdomen, cardiovascular, eyes, ears, nose, throat, general appearance, head, neck, thyroid, lymph nodes, musculoskeletal, neurological, skin / subcutaneous tissue, thorax / lungs, abdomen including spleen size, breasts (female only) and respiratory. Clinical significance of physical examination was judged by investigator.
Measured: Baseline up to end of study (up to 61 days)

Timeline

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

7 Nov 201620 Jan 2018

First posted13 Mar 2017
Study start7 Nov 2016
Primary completion19 Dec 2017
Study completion20 Jan 2018

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.
Publications (1)Papers the sponsor has linked to this study.
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
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03077607
Sponsor's protocol ID: MDV3800-04
Other IDs: C3441004, 2016-001813-26, 2016
Status last verified: Jun 2021
First submitted: 20 Jan 2017
Last updated: 30 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
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.

Publications

Elmeliegy M, Lang I, Smolyarchuk EA, Chung CH, Plotka A, Shi H, Wang D. Evaluation of the effect of P-glycoprotein inhibition and induction on talazoparib disposition in patients with advanced solid tumours. Br J Clin Pharmacol. 2020 Apr;86(4):771-778. doi: 10.1111/bcp.14178. Epub 2020 Jan 7.
PubMed 31770456

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?

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Study at a glance

From the registry record, last updated by the sponsor on 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 1 OPEN-LABEL, TWO-ARM,DRUG-DRUG INTERACTION STUDY TO EVALUATE THE EFFECT OF ITRACONAZOLE AND RIFAMPIN ON THE PHARMACOKINETICS OF TALAZOPARIB IN PATIENTS WITH ADVANCED SOLID TUMORS
ClinicalTrials.gov ID: NCT03077607
Acronym / sponsor ID: MDV3800-04
Conditions: Advanced Solid Tumors
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Collaborators: Medivation, Inc.
Study start: 7 Nov 2016 (actual)
Primary completion: 19 Dec 2017 (actual)
Study completion: 20 Jan 2018 (actual)
First posted: 13 Mar 2017 (actual)
Results: Posted 29 Mar 2019

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 study in patients with advanced solid tumors for the investigation of P-gp inhibition and induction on the PK of talazoparib.

Detailed description

Subjects participating in this study with no clinically significant toxicities and no disease progression may be eligible to continue treatment on a separate extension protocol (MDV3800-13).

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Arm A	Experimental	Drug: Talazoparib, Drug: ItraconazoleSubjects will receive a 0.5 mg talazoparib and 100 mg itraconazole.
Arm B	Experimental	Drug: Talazoparib, Drug: RifampinSubjects will receive 1 mg talazoparib and 600 mg rifampin.

Who may qualify

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

Key inclusion criteria (9 listed)

Arm A: At least 18 years of age and <65 years of age (at the time point of consent) and willing and able to provide informed consent. Arm B: At least 18 years of age (at the time point of consent) and willing and able to provide informed consent.
Histologically confirmed advanced solid tumor (limited to platinum-resistant ovarian carcinoma, cervical adenocarcinoma, small cell lung carcinoma or triple-negative breast cancer) judged by the Investigator to not be appropriate for standard therapy.
ECOG performance status ≤ 2 at screening and at time of enrollment.
Expected life expectancy of ≥ 3 months.
Able to swallow the study drug and comply with study requirements.

Key exclusion criteria (11 listed)

Treatment within 14 days or 5 half lives prior to dosing with any type of systemic anticancer therapy or any investigational agent, whichever is longer
Major surgery within 8 weeks before screening.
Serious accompanying disorder or impaired organ function.
Symptomatic or impending spinal cord compression or cauda equina syndrome.
Non-healing wound, ulcer, or bone fracture, not including a pathological bone fracture caused by a pre-existent pathological bone lesion.

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
TalazoparibArm A: 0.5 mg oral dose Arm B: 1 mg oral dose	Drug	Arm A, Arm B
Itraconazole100 mg oral dose	Drug	Arm A
Rifampin600 mg oral dose	Drug	Arm B

Primary outcome

Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Itraconazole
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Talazoparib: Alone and in Combination With Itraconazole
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
T1= Time frame for "Talazoparib 0.5 mg Alone" and T2= time frame for "Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID".
Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Rifampin
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Rifampin
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Talazoparib: Alone and in Combination With Rifampin
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
T3= Time frame for "Talazoparib 1.0 mg Alone" and T4= time frame for "Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD".

13 secondary outcomes

Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Itraconazole
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Itraconazole
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Itraconazole
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Itraconazole
Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib: Alone and in Combination With Rifampin
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Terminal Elimination Half-Life (t1/2) of Talazoparib: Alone and in Combination With Rifampin
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Talazoparib: Alone and in Combination With Rifampin
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Apparent Clearance (CL/F) of Talazoparib: Alone and in Combination With Rifampin
Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to end of study (up to 61 days)
Number of Participants With Clinical Significance Abnormalities in Laboratory Parameters
Time frame: Baseline up to end of study (up to 61 days)
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Time frame: Baseline up to end of study (up to 61 days)
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
Time frame: Baseline up to end of study (up to 61 days)
Number of Participants With Clinically Significant Physical Examination Findings
Time frame: Baseline up to end of study (up to 61 days)

Results and safety

Results posted to the registry on 29 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
A: Talazoparib 0.5 mg + Itraconazole 100 mg BID	19	17
B: Talazoparib 1 mg + Rifampin 600 mg QD	17	17

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole

Time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23. Geometric mean (Geometric Coefficient of Variation). Unit: Picogram per milliliter (pg/mL)

Measure	Talazoparib 0.5 mg Alone n = 19	Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID n = 15
Value	2092.00 (50)	2936.82 (56)

Talazoparib 0.5 mg Alone vs Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID: Geometric LS Mean Ratio: 139.92 (90% CI 113.26 to 172.87)

Population analysed: Pharmacokinetic (PK) analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.

Primary outcome: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib: Alone and in Combination With Itraconazole

Measure	Talazoparib 0.5 mg Alone n = 19	Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID n = 15
Value	98532.30 (38)	145944.59 (38)

Talazoparib 0.5 mg Alone vs Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID: Geometric LS Mean Ratio: 150.71 (90% CI 136.47 to 166.43)

Population analysed: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.

Primary outcome: Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Talazoparib: Alone and in Combination With Itraconazole

Measure	Talazoparib 0.5 mg Alone n = 18	Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID n = 12
Value	109762.10 (42)	151919.63 (36)

Talazoparib 0.5 mg Alone vs Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID: Geometric LS Mean Ratio: 156.24 (90% CI 137.58 to 177.42)

Population analysed: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters. Here, "Overall number of participants analyzed" (N) signifies those participants who were evaluable for this outcome measure.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Rifampin

Time frame: T3=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T4=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 25. Geometric mean (Geometric Coefficient of Variation). Unit: pg/mL

Measure	Talazoparib 1.0 mg Alone n = 17	Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD n = 15
Value	6007.01 (53)	8336.83 (71)

Talazoparib 1.0 mg Alone vs Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD: Geometric LS Mean Ratio: 136.62 (90% CI 103.20 to 180.87)

Population analysed: PK analysis population included all participants who enrolled, treated and had at least 1 of the talazoparib PK parameters.

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to end of study (up to 61 days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Talazoparib 0.5 mg Alone	3 of 19 (15.8%)	12 of 19 (63.2%)	1 of 19
Itraconazole 100 mg BID Alone	0 of 16 (0%)	3 of 16 (18.8%)	0 of 16
Talazoparib 0.5 mg in Combination With Itraconazole 100 mg BID	1 of 15 (6.7%)	5 of 15 (33.3%)	1 of 15
Talazoparib 1.0 mg	0 of 17 (0%)	6 of 17 (35.3%)	0 of 17
Rifampin 600 mg QD Alone	2 of 17 (11.8%)	9 of 17 (52.9%)	0 of 17
Talazoparib 1.0 mg in Combination With Rifampin 600 mg QD	0 of 15 (0%)	5 of 15 (33.3%)	0 of 15

Limitations and caveats (from the sponsor): In this study 1 participant received 2 doses of rifampin and the SAE anastomotic stenosis took place in the "rifampin" period. Originally, this SAE was attributed to the "talazoparib only" period under the assumption that the participant did not receive any dose of rifampin. This SAE was shifted from the "talazoparib only" period to the "rifampin" period.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31770456Elmeliegy M, Lang I, Smolyarchuk EA, Chung CH, Plotka A, Shi H, Wang D. Evaluation of the effect of P-glycoprotein inhibition and induction on talazoparib disposition in patients with advanced solid tumours. Br J Clin Pharmacol. 2020 Apr;86(4):771-778. doi: 10.1111/bcp.14178. Epub 2020 Jan 7.
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

7 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Talazoparib, Itraconazole and Rifampin in people with Advanced Solid Tumors, run by Pfizer at 7 sites in 4 countries.

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 9 inclusion and 11 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 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Russia, Hungary, Moldova, Poland. 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 29 Mar 2019). 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?

Maximum Observed Plasma Concentration (Cmax) of Talazoparib: Alone and in Combination With Itraconazole (time frame: T1=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 1; T2=Predose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 and 336 hours post Talazoparib dose on Day 23). The study lists 6 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 NCT03077607, which also lists 1 linked publication.

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 30 Jun 2021.