Pharmacokinetics of DextromethorphanPhase 1NCT02225093
A Study to Evaluate How Daily Dosing With Enzalutamide Affects the Metabolism of Caffeine and Dextromethorphan in Men With Prostate Cancer
A Phase 1 study testing Caffeine, Dextromethorphan and Enzalutamide in people with Pharmacokinetics of Dextromethorphan and Pharmacokinetics of Caffeine, run by Astellas Pharma Europe B.V. at 1 site in Moldova.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Pharmacokinetics of Dextromethorphan, Pharmacokinetics of Caffeine, Prostate Cancer
- What is being tested?
- Caffeine, Dextromethorphan and Enzalutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteMoldova
- Study dates
- 2 Oct 2013to 3 Feb 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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.
Read the 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.
- Being tested
- Caffeine, Dextromethorphan, Enzalutamide, Enzalutamide Placebo to Match (PTM)
- Keywords
- Safety, Dextromethorphan, CYP2D6, Phase 1, Prostate cancer, CYP1A2, Pharmacokinetics, Drug-drug interactions, Caffeine, Enzalutamide
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDrug
Also called CYP1A2 substrate
Oral
DextromethorphanDrug
Also called CYP2D6 substrate
Oral /.L
EnzalutamideDrug
Also called Xtandi, MDV3100, ASP9785
Oral
Enzalutamide Placebo to Match (PTM)Drug
Oral
| Study group | Role | What they receive |
|---|---|---|
| 1:Caffeine, Dextromethorphan and Enzalutamide | Experimental | 1-sequence crossover here Receives: Drug: Caffeine; Drug: Dextromethorphan; Drug: Enzalutamide; Drug: Enzalutamide Placebo to Match (PTM) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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)
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.
Measured: Day 1 and Day 53 (28 times)
PK measured by PK parameters Cmax, AUC0-t, AUC0-inf, %AUC, tmax and t1/2
For 1,7-dimethylxanthine (metabolite caffeine), dextrorphan (metabolite dextromethorphan).
Measured: 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)
For Enzalutamide, N-desmethyl enzalutamide (M2) and sum of enzalutamide + M2.
Measured: Day 28 (± 1 day), and Days 52 to 55 (15 times)
Safety and tolerability measured by vital signs, adverse events, laboratory assessments and electrocardiogram
Measured: Screening (Day -28 to Day -7) to ESV (>153 times)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2014 (estimated)
- Study start2 Oct 2013
- Primary completion3 Feb 2014
- Study completion3 Feb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharmacokinetics of DextromethorphanStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Europe B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medivation, Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Astellas Pharma Europe B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02225093
- Sponsor's protocol ID
- 9785-CL-0406
- Status last verified
- Jun 2017
- First submitted
- 22 Aug 2014
- Last updated
- 27 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02225093
- Acronym / sponsor ID
- 9785-CL-0406
- Keywords
- Safety, Dextromethorphan, CYP2D6, Phase 1, Prostate cancer, CYP1A2, Pharmacokinetics, Drug-drug interactions
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Collaborators
- Medivation, Inc.
- Study start
- 2 Oct 2013 (actual)
- Primary completion
- 3 Feb 2014 (actual)
- Study completion
- 3 Feb 2014 (actual)
- First posted
- 26 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1:Caffeine, Dextromethorphan and Enzalutamide | Experimental | Drug: Caffeine, Drug: Dextromethorphan, Drug: Enzalutamide, Drug: Enzalutamide Placebo to Match (PTM)1-sequence crossover here |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CaffeineAlso: CYP1A2 substrateOral | Drug | 1:Caffeine, Dextromethorphan and Enzalutamide |
| DextromethorphanAlso: CYP2D6 substrateOral /.L | Drug | 1:Caffeine, Dextromethorphan and Enzalutamide |
| EnzalutamideAlso: Xtandi, MDV3100, ASP9785Oral | Drug | 1:Caffeine, Dextromethorphan and Enzalutamide |
| Enzalutamide Placebo to Match (PTM)Oral | Drug | 1:Caffeine, Dextromethorphan and Enzalutamide |
Primary outcome
PK measured by Pharmacokinetic parameter Maximum concentration (Cmax)
Time frame: Day 1 and Day 53 (28 times)
For the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.
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)
For the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.
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)
For the probe substrates (caffeine and dextromethorphan) in combination with enzalutamide PTM and in combination with enzalutamide.
4 secondary outcomes
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)
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)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2017.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Astellas Pharma Europe B.V.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Caffeine, Dextromethorphan and Enzalutamide in people with Pharmacokinetics of Dextromethorphan and Pharmacokinetics of Caffeine, run by Astellas Pharma Europe B.V. at 1 site in Moldova.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Moldova. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK measured by Pharmacokinetic parameter Maximum concentration (Cmax) (time frame: Day 1 and Day 53 (28 times)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2017.