Clinical Trial: A Safety Study of JNJ-56021927 in Participants With Metastatic Castration-Resistant Prostate Cancer
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: A Phase 1 Study of Androgen Receptor (AR) Antagonist JNJ-56021927 in Subjects With Metastatic Castration-Resistant Prostate Cancer
Brief Summary: The purpose of this study is to evaluate the safety and tolerability of JNJ-56021927 in Japanese participants with metastatic castration-resistant prostate cancer (mCRPC- prostate cancer that is resistant to medical [for example. hormonal] or surgical treatments).
Detailed Summary: This is a Phase 1, multicenter, open-label (participants will know the identity of study drug received) study in participants with Metastatic Castration-Resistant Prostate Cancer (mCRPC). The study consists of 4 parts: Screening (28 days before study commences on Day 1), pharmacokinetic week (PK), Continuous daily dosing, Extension and Safety follow-up period. In PK week participants will receive a single oral capsule of JNJ-56021927 at a dose of 240 milligram (mg) on Day 1 and will be monitored for 1 week. After Week 1, in continuous daily dosing period, participants will receive continuous daily therapy at the same dose for 4 weeks (Cycle 1). After Cycle 1 participants, who will not meet the criteria for discontinuation listed such as progressive disease (PD) or unacceptable toxicity, will continue in safety follow-up period and will receive continuous daily therapy at the same dose up to cycle 13. Primarily dose limiting toxicity (DLT) will be evaluated. Participants' safety will be monitored throughout.
Sponsor: Janssen Pharmaceutical K.K.
Current Primary Outcome: Number of Participants With Dose Limiting Toxicity [ Time Frame: Week 1 up to Day 28 of Cycle 1 ]
Original Primary Outcome: Number of Participants With Dose Limiting Toxicity [ Time Frame: up to Day 28 of Cycle 1 ]
Current Secondary Outcome:
- Maximum Observed Plasma Concentration (C[max]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]The C(max) is the maximum plasma concentration which will be observed at the defined time points.
- Time to Reach the Maximum Plasma Concentration (T[max]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]The T[max] is time to reach the observed maximum plasma concentration.
- Elimination Half-life (t1/2[lambda]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]Elimination half-life associated with the terminal slope (lambda[z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda (z).
- Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.
- Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]The AUC (0-last) is the area under the plasma concentration-time curve from time zero time of the last quantifiable concentration C(last), and C(last) is the last observed quantifiable concentration.
- Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]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(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
- Change in Prostate-specific Antigen (PSA) [ Time Frame: Baseline, Day 1 of each cycle (28 days) until disease progression and up to 28 days after the last dose study drug ]Change in prostate specific antigen will be assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria and Response Criteria in Solid Tumors (RECIST). PSA progression will delayed if decline from baseline: greater than or equal to (>=) 25 percent (%) and >= 2 nanogram per milliliter (ng/mL) above the PSA nadir, which is confirmed by a second value 3 or more weeks later; and no decline from baseline: PSA progression >= 25% and >= 2 ng/mL after 12 weeks.
- Trough Plasma Concentration (C[trough]) [ Time Frame: Pre- dose on Day 1 of Cycle 2 up to Cycle 13 ]Trough plasma concentration (C[trough]) just before dosing will be assessed.
- Observed Accumulation Index (A[cc] Index) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug in Cycle 1 ]Observed Accumulation Index (A[cc] Index) will be calculated as AUC[0-24] at steady state divided by AUC[0-24].
- Effective Half-life (EHL) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug in Cycle 1 ]Effective Half-life (EHL) will be calculated as dosing interval minus log 2 divided by log {1-[1/A[cc]Index}.
- Percent Peak to Trough Fluctuation (PTF) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug in Cycle 1 ]Percent Peak to Trough Fluctuation (PTF) will be calculated as 100 multiplied by {C[max]/C[min]}.
Original Secondary Outcome:
- Maximum Observed Plasma Concentration (C[max]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]The C(max) is the maximum plasma concentration which will be observed at the defined time points.
- Time to Reach the Maximum Plasma Concentration (T[max]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]The T[max] is time to reach the observed maximum plasma concentration.
- Elimination Half-life (t1/2[lambda]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]Elimination half-life associated with the terminal slope (lambda[z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda (z).
- Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.
- Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]The AUC (0-last) is the area under the plasma concentration-time curve from time zero time of the last quantifiable concentration C(last), and C(last) is the last observed quantifiable concentration.
- Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]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(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
- Change in Prostate-specific Antigen (PSA) [ Time Frame: Baseline, Day 1 of each cycle (28 days) until disease progression and up to 28 days after the last dose study drug ]Change in prostate specific antigen will be assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria and Response Criteria in Solid Tumors (RECIST). PSA progression will dealyed if decline from baseline: greater than or equal to (>=) 25 percent (%) and >= 2 nanogram per milliliter (ng/mL) above the PSA nadir, which is confirmed by a second value 3 or more weeks later; and no decline from baseline: PSA progression >= 25% and >= 2 ng/mL after 12 weeks.
- Trough Plasma Concentration (C[trough]) [ Time Frame: Pre- dose on Day 1 of Cycle 2 up to Cycle 13 ]Trough plasma concentration (C[trough]) just before dosing will be assessed.
- Observed Accumulation Index (A[cc] Index) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug in Cycle 1 ]Observed Accumulation Index (A[cc] Index) will be calculated as AUC[0-24] at steady state divided by AUC[0-24].
- Effective Half-life (EHL) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug in Cycle 1 ]Effective Half-life (EHL) will be calculated as dosing interval minus log 2 divided by log {1-[1/A[cc]Index}.
- Percent Peak to Trough Fluctuation (PTF) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug in Cycle 1 ]Percent Peak to Trough Fluctuation (PTF) will be calculated as 100 multiplied by {C[max]/C[min]}.
Information By: Janssen Pharmaceutical K.K.
Dates:
Date Received: June 11, 2014
Date Started: June 27, 2014
Date Completion: September 17, 2018
Last Updated: April 13, 2017
Last Verified: April 2017