Clinical trial 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Prostatic Neoplasms, Castration-Resistant
Keywords: JNJ-56021927
Prostatic Neoplasms, Castration-Resistant
Lead sponsor: Aragon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-10-30
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 1, 8, 9, 43, 50, and 51
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
timeFrame: Day 1, 8, 9, 43, 50, and 51
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
timeFrame: Day 1, 8, 9, 43, 50, and 51
Secondary outcomes:
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Days 1, 8, 9, 43, 50, and 51
measure: Elimination Rate Constant (Lambda[z])
timeFrame: Day 1, 8, 9, 43, 50, and 51
measure: Elimination Half-Life (t1/2)
timeFrame: Days 1, 8, 9, 43, 50, and 51
measure: Apparent Clearance (CL/F)
timeFrame: Days 1, 8, 9, 43, 50, and 51
measure: Maximum Observed Plasma Concentration (Cmax) for JNJ-56021927
timeFrame: Day 43
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for JNJ-56021927
timeFrame: Day 43
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24])
timeFrame: Day 43
measure: Trough Plasma Concentration (Ctrough)
timeFrame: Day 43, 50 and 51
measure: Number of Participants with Adverse Events
timeFrame: Up to 6 years 6 months
Other outcomes:
Locations:
city: Chisinau
country: Moldova, Republic of
facility: Arensia Exploratory Medicine
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: