- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02225093
A Study to Evaluate How Daily Dosing With Enzalutamide Affects the Metabolism of Caffeine and Dextromethorphan in Men With Prostate Cancer
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
Study Overview
Status
Intervention / Treatment
Detailed Description
This is an open-label, fixed-sequence, crossover drug-drug interaction study in subjects with prostate cancer.
Screening takes place between Day -28 and Day -7, and subjects are admitted to the clinic on Day -1 where they remain until Day 4.
On Day 1, they receive a single oral cocktail containing caffeine and dextromethorphan plus a dose of enzalutamide placebo in order to assess possible effects of excipients of the enzalutamide formulation. On Days 1 to 3 blood samples for pharmacokinetic (PK) assessment are collected. From Days 4 to 54, (or Day 55 if the subject rolls over into the extension study) the subjects take a daily oral dose of enzalutamide. On Day 28, the subjects return to the clinic where a plasma sample is taken to determine enzalutamide PK exposure. From Days 52 to 55 they are re-admitted to the clinic where a plasma sample is collected on Day 52 for enzalutamide PK exposure.On Day 53, subjects receive a single oral cocktail of caffeine and dextromethorphan concomitantly with enzalutamide. PK samples are collected from Days 53 to 55.
From Day 55 onwards, subjects experiencing clinical benefit may roll over into an extension study. Only subjects who enroll into the extension study continue to receive enzalutamide otherwise daily dosing with enzalutamide is discontinued on Day 54.
An End of Study Visit (ESV) takes place approximately 30 days (±7 days) after the last dose of enzalutamide.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
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Chisinau, Moldova, Republic of, 2025
- ARENSIA
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1:Caffeine, Dextromethorphan and Enzalutamide
1-sequence crossover here
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Oral
Other Names:
Oral
Other Names:
Oral /.L
Other Names:
Oral
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PK measured by Pharmacokinetic parameter Maximum concentration (Cmax)
Time Frame: Day 1 and Day 53 (28 times)
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For the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.
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Day 1 and Day 53 (28 times)
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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)
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For the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.
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Day 1 and Day 53 (28 times)
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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)
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For the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.
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Day 1 and Day 53 (28 times)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
Tmax is time to maximum concentration.
These PK parameters will be measured for the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.
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Day 1 and Day 53 (28 times)
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PK measured by PK parameters Cmax, AUC0-t, AUC0-inf, %AUC, tmax and t1/2
Time Frame: Day 1 and Day 53 (28 times)
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For 1,7-dimethylxanthine (metabolite caffeine), dextrorphan (metabolite dextromethorphan).
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Day 1 and Day 53 (28 times)
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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)
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For Enzalutamide, N-desmethyl enzalutamide (M2) and sum of enzalutamide + M2.
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Day 28 (± 1 day), and Days 52 to 55 (15 times)
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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)
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Screening (Day -28 to Day -7) to ESV (>153 times)
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Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Purinergic Antagonists
- Purinergic Agents
- Respiratory System Agents
- Phosphodiesterase Inhibitors
- Purinergic P1 Receptor Antagonists
- Central Nervous System Stimulants
- Antitussive Agents
- Dextromethorphan
- Caffeine
Other Study ID Numbers
- 9785-CL-0406
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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