A Study to Evaluate How Daily Dosing With Enzalutamide Affects the Metabolism of Caffeine and Dextromethorphan in Men With Prostate Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02225093
• Date of registration: 22/08/2014
• Prospective Registration: No
• Primary sponsor: Astellas Pharma Europe B.V.
• Public title: A Study to Evaluate How Daily Dosing With Enzalutamide Affects the Metabolism of Caffeine and Dextromethorphan in Men With Prostate Cancer
• Scientific title: A Phase 1 Open-label Study to Evaluate the Effect of Multiple Doses of Enzalutamide on the Pharmacokinetics of Substrates for CYP1A2 and CYP2D6 in Male Subjects With Prostate Cancer
• Date of first enrolment: October 2, 2013
• Target sample size: 12
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02225093
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Crossover Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Moldova, Republic of

Contacts

• Name: Medical Director
• Affiliation: Astellas Pharma Europe B.V.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subject is a male aged 18 years old or older (at screening) with histologically
confirmed prostate cancer (all stages) for whom androgen deprivation therapy is
indicated (except when indicated in a neoadjuvant/adjuvant setting). Subjects may be
on ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH)
analogue or have undergone prior bilateral orchiectomy at screening.

- Subject has progressive disease by prostate-specific antigen (PSA) or imaging.

- Subject has received no more than 2 prior chemotherapy regimens.

- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

- Male subject must use a condom if having sex with a pregnant woman.

- Male subject and their female spouse/partners who are of childbearing potential must
use 2 acceptable methods of birth control starting at screening and continuing
throughout the study period and for 3 months after final study drug administration.

- Subject has an estimated life expectancy of at least 6 months.

Exclusion Criteria:

- Subject has confirmed CYP2D6 poor metabolizer, or CYP2D6 ultrarapid metabolizer status
based on genotyping analysis.

- Subject has known metastases in the liver or any hepatic disorder that could affect
drug metabolism deemed clinically significant by the investigator after discussion
with the sponsor.

- Subject has undergone major surgery within 4 weeks prior to day 1.

- Subject received treatment with chemotherapy within 4 weeks prior to enrollment (day 1
visit) or plans to initiate treatment with chemotherapy during the study.

- Subject uses concomitant medications that are potent inducers and/or inhibitors of
CYP1A2, CYP2C8, CYP2D6, or CYP3A4.



Age minimum: 18 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Pharmacokinetics of Dextromethorphan

Pharmacokinetics of Caffeine

Prostate Cancer

Intervention(s)

Drug: Caffeine

Drug: Enzalutamide Placebo to Match (PTM)

Drug: Dextromethorphan

Drug: Enzalutamide

Primary Outcome(s)

PK measured by PK parameter area under the curve (AUC) from time 0 extrapolated to infinity (AUC0-inf) [Time Frame: Day 1 and Day 53 (28 times)]

PK measured by Pharmacokinetic parameter Area under the curve (AUC) from the time of dosing to the last measurable concentration (AUC0-t) [Time Frame: Day 1 and Day 53 (28 times)]

PK measured by Pharmacokinetic parameter Maximum concentration (Cmax) [Time Frame: Day 1 and Day 53 (28 times)]

Secondary Outcome(s)

PK measured by PK parameters Cmax, trough concentrations (Ctrough) at Days 28, 52, 53, 54 and 55, tmax, AUC during the time interval between consecutive dosing (AUCtau), CL/F (parent only) and peak-to-trough ratio (PTR) [Time Frame: Day 28 (± 1 day), and Days 52 to 55 (15 times)]

PK measured by PK parameters tmax, terminal elimination half-life (t1/2), apparent total systemic clearance after oral dosing (CL/F), apparent volume of distribution during terminal elimination phase (Vz/F) and extrapolated AUC (%AUC) [Time Frame: Day 1 and Day 53 (28 times)]

PK measured by PK parameters Cmax, AUC0-t, AUC0-inf, %AUC, tmax and t1/2 [Time Frame: Day 1 and Day 53 (28 times)]

Safety and tolerability measured by vital signs, adverse events, laboratory assessments and electrocardiogram [Time Frame: Screening (Day -28 to Day -7) to ESV (>153 times)]

Secondary ID(s)

9785-CL-0406

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Medivation, Inc.