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

NCT02592317 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: CR10807256021927PCR10202015-003691-72
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 3

Brief 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).

Conditions

Prostatic Neoplasms, Castration-Resistant

Keywords

JNJ-56021927; Prostatic Neoplasms, Castration-Resistant

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (Cmax)

  Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Cmax for Midazolam, S-warfarin, omeprazole, fexofenadine, pioglitazone, rosuvastatin will be assessed along with the metabolites of Midazolam, S-warfarin, omeprazole and pioglitazone.

  Day 1, 8, 9, 43, 50, and 51

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])

  The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time. AUC (0-last) for Midazolam, S-warfarin, omeprazole, fexofenadine, pioglitazone, rosuvastatin will be assessed along with the metabolites of Midazolam, S-warfarin, omeprazole and pioglitazone.

  Day 1, 8, 9, 43, 50, and 51

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])

  The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant. AUC\[0-infinity\]) for Midazolam, S-warfarin, omeprazole, fexofenadine, pioglitazone, rosuvastatin will be assessed along with the metabolites of Midazolam, S-warfarin, omeprazole and pioglitazone.

  Day 1, 8, 9, 43, 50, and 51

Secondary Outcomes (9)

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  Days 1, 8, 9, 43, 50, and 51

• Elimination Rate Constant (Lambda[z])

  Day 1, 8, 9, 43, 50, and 51

• Elimination Half-Life (t1/2)

  Days 1, 8, 9, 43, 50, and 51

• Apparent Clearance (CL/F)

  Days 1, 8, 9, 43, 50, and 51

• Maximum Observed Plasma Concentration (Cmax) for JNJ-56021927

  Day 43

Study Arms (1)

JNJ 56021927

EXPERIMENTAL

Participants will receive drug cocktail (comprising of midazolam \[2 milligram {mg}\], warfarin \[10 mg\], vitamin K (10 mg), omeprazole (40 mg), and fexofenadine \[30 mg\]) orally on Study Day 1 and 43 (Cycle 2 Day 1). On Study Day 8 and 50, pioglitazone 15 mg will be administered orally and on Study Day 9 and 51, rosuvastatin 10 mg will be administered orally. JNJ 56021927, 240 mg once daily will be administered on 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: JNJ 56021927; Drug: Drug Cocktail; Drug: Pioglitazone; Drug: Rosuvastatin

Interventions

JNJ 56021927 DRUG

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.

JNJ 56021927

Rosuvastatin DRUG

Rosuvastatin 15 mg will be administered orally on Study Day 9 and 51.

JNJ 56021927

Drug Cocktail DRUG

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.

JNJ 56021927

Pioglitazone DRUG

Pioglitazone 15 mg will be administered orally on Study Day 8 and 50.

JNJ 56021927

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Adenocarcinoma of the prostate
• Participants with non-metastatic castration-resistant prostate cancer (NM-CRPC) or metastatic castration-resistant prostate cancer (mCRPC), who in the opinion of the investigator may benefit from treatment with JNJ-56021927
• Surgically or medically castrated, with testosterone levels of \<50 nanogram per deciliter (ng/dL)
• If the participant is being treated with a gonadotropin-releasing hormone (GnRHa) (ie, participant who has not undergone bilateral orchiectomy), then this therapy must have been initiated at least 4 weeks prior to the Cycle 1 Day 1 visit and must be continued throughout the study
• Adequate bone marrow and organ function defined as: Hemoglobin (\>=9.0 g/dL, independent of transfusion or growth factor support within the prior 7 days); Absolute neutrophil count (\>=1000/mm\^3 independent of growth factor support within the prior 7 days); Platelet count (\>=75,000/mm\^3 independent of transfusion or growth factor support within the prior 7 days); Serum albumin (\>=3.0 g/dL); Serum creatinine (\<=1.5\*upper limit of normal (ULN) or calculated creatinine clearance \>=50 mL/min/1.73m\^2); Total bilirubin \[\<1.5\*ULN (participants with Gilbert's Syndrome may be enrolled if the total bilirubin is \<4 mg/dL with predominance of indirect bilirubin \>=80% of total bilirubin\]); Aspartate aminotransferase or alanine aminotransferase (\<=3.0\*ULN); Prothrombin time (PT) or partial thromboplastin time (PTT) or international normalized ratio (INR) (PT \<=15 sec or INR \<=1.2 PTT \<=40 sec).

You may not qualify if:

• Known brain metastases
• Chemotherapy or immunotherapy for the treatment of prostate cancer within 4 weeks of the Study Day 15 (Cycle 1 Day 1) visit
• Prior treatment with enzalutamide within 8 weeks before first dose of drug probes
• Therapies that must be discontinued or substituted prior to study visit Day 1, or must be temporarily interrupted during the course of the study, include the following: a) Medications known to lower the seizure threshold within 4 weeks before Study Day 15 (Cycle 1 Day 1) and b) Medications known to induce or inhibit drug metabolizing enzymes (CYP3A4, CYP2C9, CYP2C19 and CYP2C8) or transporter proteins (P-gp, BRCP, OATP1B1, and OATPB3)
• Participant has known allergies, hypersensitivity, or intolerance to any of the study drugs/drug probes or excipients
• History of seizure or any condition that may predispose to seizure within 12 months prior to enrollment (Study Day 1); brain arteriovenous malformation; or intercranial masses such as schwannoma or meningioma that is causing edema or mass effect
• Participants with poor metabolizer genotype for CYP2C9 (\*2, \*3), or CYP2C19 (\*2, \*3, \*4, \*8)

Sponsors & Collaborators

• Aragon Pharmaceuticals, Inc.: lead

Study Sites (3)

Unknown Facility

Chisinau, Moldova

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Seville, Spain

Location

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

Pioglitazone; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Pyrimidines

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2015
• First Posted: October 30, 2015
• Study Start: February 12, 2016
• Primary Completion: November 7, 2016
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

ES (2); MO (1)