NCT02592317

A Study to Evaluate the Effect of Multiple Doses of JNJ-56021927 on the Pharmacokinetics of Multiple Cytochrome P450 and Transporter Substrates in Participants With Castration-Resistant Prostate Cancer

Drug-drug Interaction Study to Evaluate the Effect of Multiple Doses of JNJ-56021927 on the Pharmacokinetics of Multiple Cytochrome P450 and Transporter Substrates in Subjects With Castration-Resistant Prostate Cancer

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Aragon Pharmaceuticals, Inc. · Industry
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the effects of repeat dosing of JNJ-56021927 on the pharmacokinetics for single-dose multiple cytochrome P450 (CYP450) enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2C8) and transporter (P-gp and BRCP) substrates in participants with castration-resistant prostate cancer (CRPC).

Detailed description

This is a Phase 1, multicenter, open-label study in participants with CRPC. The study will consist of a Screening Phase to determine eligibility, a Pretreatment Phase, a Treatment Phase, and a Follow-up Phase. The study is designed to estimate the magnitude of the effects of JNJ-56021927 on the pharmacokinetics of probe substrates. In vitro studies have indicated that JNJ-56021927 and its active metabolite JNJ-56142060 (M3) have the potential to affect multiple cytochrome P450 (CYP) enzymes (CYP3A4, CYP2C9, CYP2C19, and CYP2C8) and drug transporters proteins (P-glycoprotein \[P-gp\] and breast cancer resistance protein \[BRCP\]) via inhibition or induction. In human hepatocytes, JNJ 56021927 and JNJ-56142060 (M3) were found to be inducers of CYP3A4. The induction of CYP3A4 suggests that JNJ-56021927 and M3 will induce other CYP isozymes and drug transporters (eg, CYP2C and P-gp via activation of pregnane X receptor). The study is designed to confirm the in vivo significance of these non-clinical findings.

Conditions

• Prostatic Neoplasms, Castration-Resistant

Interventions

Type	Name	Description
DRUG	JNJ 56021927	JNJ 56021927 will be administered once daily orally in a dose of 240 mg from Study Day 15 up to disease progression, unacceptable toxicity, withdrawal of consent, lost to follow-up, the participant is no longer receiving clinical benefit in the opinion of the Investigator, the start of subsequent anticancer therapy, or the Sponsor ends the study.
DRUG	Drug Cocktail	Drug cocktail comprise of midazolam (2 mg), warfarin (10 mg), vitamin K (10 mg), omeprazole (40 mg), and fexofenadine (30 mg) will be administered on Study Day 1 and 43.
DRUG	Pioglitazone	Pioglitazone 15 mg will be administered orally on Study Day 8 and 50.
DRUG	Rosuvastatin	Rosuvastatin 15 mg will be administered orally on Study Day 9 and 51.

Timeline

• Start date: 2016-02-12
• Primary completion: 2016-11-07
• Completion: 2027-12-31
• First posted: 2015-10-30
• Last updated: 2026-04-13

Locations

3 sites across 2 countries: Moldova, Spain

Regulatory

• FDA-regulated drug study