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

NCT02225093 | Completed Phase 1

• 1 other identifier: 9785-CL-0406
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates how once daily enzalutamide affects the metabolism of caffeine and dextromethorphan in men with prostate cancer by measuring concentrations of these drugs and their metabolites in plasma.

Conditions

Pharmacokinetics of Dextromethorphan; Pharmacokinetics of Caffeine; Prostate Cancer

Keywords

Safety; Dextromethorphan; CYP2D6; Phase 1; Prostate cancer; CYP1A2; Pharmacokinetics; Drug-drug interactions; Caffeine; Enzalutamide

Outcome Measures

Primary Outcomes (3)

• PK measured by Pharmacokinetic parameter Maximum concentration (Cmax)

  For the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.

  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)

  For the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.

  Day 1 and Day 53 (28 times)

• PK measured by PK parameter area under the curve (AUC) from time 0 extrapolated to infinity (AUC0-inf)

  For the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.

  Day 1 and Day 53 (28 times)

Secondary Outcomes (4)

• 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)

  Day 1 and Day 53 (28 times)

• PK measured by PK parameters Cmax, AUC0-t, AUC0-inf, %AUC, tmax and t1/2

  Day 1 and Day 53 (28 times)

• 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)

  Day 28 (± 1 day), and Days 52 to 55 (15 times)

• Safety and tolerability measured by vital signs, adverse events, laboratory assessments and electrocardiogram

  Screening (Day -28 to Day -7) to ESV (>153 times)

Study Arms (1)

1:Caffeine, Dextromethorphan and Enzalutamide

EXPERIMENTAL

1-sequence crossover here

Drug: Caffeine; Drug: Dextromethorphan; Drug: Enzalutamide; Drug: Enzalutamide Placebo to Match (PTM)

Interventions

Caffeine DRUG

Oral

Also known as: CYP1A2 substrate

1:Caffeine, Dextromethorphan and Enzalutamide

Dextromethorphan DRUG

Oral /.L

Also known as: CYP2D6 substrate

1:Caffeine, Dextromethorphan and Enzalutamide

Enzalutamide DRUG

Oral

Also known as: Xtandi, MDV3100, ASP9785

1:Caffeine, Dextromethorphan and Enzalutamide

Enzalutamide Placebo to Match (PTM) DRUG

Oral

1:Caffeine, Dextromethorphan and Enzalutamide

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead
• Medivation, Inc.: collaborator

Study Sites (1)

Arensia

Chisinau, 2025, Moldova

Location

Related Links

• Link to results on Astellas Clinical Study Results website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Caffeine; Dextromethorphan; enzalutamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Medical Director

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2014
• First Posted: August 26, 2014
• Study Start: October 2, 2013
• Primary Completion: February 3, 2014
• Study Completion: February 3, 2014
• Last Updated: June 27, 2017

Record last verified: 2017-06

Locations

MO (1)