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

NCT03077607 | Completed Phase 1 Results

• 3 other identifiers: MDV3800-04C34410042016-001813-26
• Study Type: interventional
• Target: 36
• Locations: 4 countries
• Sites: 7

Brief 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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (6)

• 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".

  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".

  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".

  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".

  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".

  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".

  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=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

  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

  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

  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=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

Study Arms (2)

Arm A

EXPERIMENTAL

Subjects will receive a 0.5 mg talazoparib and 100 mg itraconazole.

Drug: Talazoparib; Drug: Itraconazole

Arm B

EXPERIMENTAL

Subjects will receive 1 mg talazoparib and 600 mg rifampin.

Drug: Talazoparib; Drug: Rifampin

Interventions

Talazoparib DRUG

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

Arm A; Arm B

Itraconazole DRUG

100 mg oral dose

Arm A

Rifampin DRUG

600 mg oral dose

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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 \[e.g. opiates for pain relief\].

Sponsors & Collaborators

• Pfizer: lead
• Medivation, Inc.: collaborator

Study Sites (7)

PRA Magyarorszag Kft, Fazis I-es Klinikai Farmakologiai Vizsgalohely

Budapest, 1077, Hungary

Location

ARENSIA Exploratory Medicine Phase I Unit, PMSI Institute of Oncology

Chisinau, MD2025, Moldova

Location

Szpital LUX MED

Warsaw, 02-801, Poland

Location

I.M. Sechenov First Moscow State Medical University

Moscow, 119435, Russia

Location

I.M. Sechenov First Moscow State Medical University

Moscow, 119991, Russia

Location

"BioEq" LLC

Saint Petersburg, 197342, Russia

Location

State budget healthcare institution of Yaroslavl region "Regional clinical oncology hospital"

Yaroslavl, 150054, Russia

Location

Related Publications (1)

• 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.

  PMID: 31770456 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

talazoparib; Itraconazole; Rifampin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

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.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: March 13, 2017
• Study Start: November 7, 2016
• Primary Completion: December 19, 2017
• Study Completion: January 20, 2018
• Last Updated: June 30, 2021
• Results First Posted: March 29, 2019

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

MO (1); RU (4); PL (1); HU (1)