Effect of Probenecid on Pexidartinib Pharmacokinetics

NCT03138759 | Completed Phase 1 FDA Drug

• 1 other identifier: PL3397-A-U122
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this trial is to assess the effect of probenecid on the pharmacokinetics (PK) of single-dose pexidartinib in healthy subjects. Secondary objectives are to assess the safety and tolerability of pexidartinib alone and in combination with probenecid. Participants will be confined to the clinic for approximately 32 days. Blood samples will be collected for PK analysis of pexidartinib and metabolites at predose and up to 312 hours (h) post dose.

Conditions

Pharmacokinetics in Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration (Cmax)

  Maximum concentration of the drug and its metabolite in plasma

  predose to 312 hours post dose

• Time to Maximum Concentration (Tmax)

  Time at which the maximum concentration is reached

  within 312 hours post dose

• Area under the curve to the last quantifiable measurement (AUClast)

  Area under the drug concentration time curve from the first measurement to the last

  within 312 hours post dose

Secondary Outcomes (1)

• Number of participants experiencing an adverse event

  within 312 hours post dose

Study Arms (2)

Pexidartinib then Probenecid

EXPERIMENTAL

Participants receive Sequence AB: Treatment A (pexidartinib) first, then Treatment B (probenecid), with a washout period between them

Drug: Pexidartinib; Drug: Probenecid

Probenecid then Pexidartinib

EXPERIMENTAL

Participants receive Sequence BA: Treatment B (probenecid) first, then Treatment A (pexidartinib), with a washout period between them

Drug: Pexidartinib; Drug: Probenecid

Interventions

Pexidartinib DRUG

Orally, on Day 2

Also known as: Treatment A

Pexidartinib then Probenecid; Probenecid then Pexidartinib

Probenecid DRUG

Orally, on Day 2

Also known as: Treatment B

Pexidartinib then Probenecid; Probenecid then Pexidartinib

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is a healthy, nonsmoking person with a body mass index of 18 kg/m2 to 30 kg/m2 (inclusive) at Screening
• Is willing to be confined at the clinic for approximately 32 days
• Is surgically sterile or a naturally postmenopausal female and not lactating, or a male who agrees to use double barrier methods of contraception and avoid donating sperm from Check-in until 90 d after the final dose of pexidartinib

You may not qualify if:

• Has any history or condition, per protocol or in the opinion of the investigator, that might compromise the participant's safety, their ability to complete the trial, and or analysis of results

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (1)

Worldwide Clinical Trials Early Phase Services

San Antonio, Texas, 78217, United States

Location

Related Publications (1)

• Zahir H, Greenberg J, Shuster D, Hsu C, Watanabe K, LaCreta F. Evaluation of Absorption and Metabolism-Based DDI Potential of Pexidartinib in Healthy Subjects. Clin Pharmacokinet. 2022 Nov;61(11):1623-1639. doi: 10.1007/s40262-022-01172-9. Epub 2022 Oct 20.

  PMID: 36264536 DERIVED

MeSH Terms

Interventions

pexidartinib; Probenecid

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Clinical Study Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, 2-treatment sequence, 2-period, crossover study with a washout between doses and treatment periods

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 3, 2017
• Study Start: February 27, 2017
• Primary Completion: March 30, 2017
• Study Completion: March 30, 2017
• Last Updated: May 3, 2017

Record last verified: 2017-05

Locations

US (1)