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

Pfizer36 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumors

Interventions

TalazoparibDRUG

Arm A: 0.5 mg oral dose Arm B: 1 mg oral dose

ItraconazoleDRUG

100 mg oral dose

RifampinDRUG

600 mg oral dose

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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. 2. 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. 3. ECOG performance status ≤ 2 at screening and at time of enrollment. 4. Expected life expectancy of ≥ 3 months. 5. Able to swallow the study drug and comply with study requirements. 6. 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. 7. 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. 8. Female subjects must not be breastfeeding at screening and during the study participation until 45 days after the last dose of the study drug. 9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Exclusion Criteria: 1. 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 2. Major surgery within 8 weeks before screening. 3. Serious accompanying disorder or impaired organ function. 4. Symptomatic or impending spinal cord compression or cauda equina syndrome. 5. Non-healing wound, ulcer, or bone fracture, not including a pathological bone fracture caused by a pre-existent pathological bone lesion. 6. Known myelodysplastic syndrome. 7. Subjects with the following serologies should be excluded: HBsAg+ or anti-HBc+;HCV+; HIV+. 8. Serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol. 9. Gastrointestinal disorder affecting absorption. 10. Known hypersensitivity to any of the talazoparib capsule components. 11. 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 \[e.g. opiates for pain relief\].

Locations (7)

PRA Magyarorszag Kft, Fazis I-es Klinikai Farmakologiai Vizsgalohely

Budapest, Hungary

ARENSIA Exploratory Medicine Phase I Unit, PMSI Institute of Oncology

Chisinau, Moldova

Szpital LUX MED

Warsaw, Poland

I.M. Sechenov First Moscow State Medical University

Moscow, Russia

Outcomes

Primary Outcomes

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".

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

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".

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".

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".

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

Data from ClinicalTrials.gov

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Secondary Outcomes

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".

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".

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".

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".

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".

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".

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".

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".

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.