Cerebrovascular CirculationPhase 1NCT03704519
Imaging Study to Compare Effects of Darolutamide and Enzalutamide With Respect to Placebo on the Blood Flow in the Brain in Healthy Male Volunteers.
A Phase 1 study testing Darolutamide (BAY1841788) and Enzalutamide in people with Cerebrovascular Circulation, run by Bayer at 1 site in United Kingdom.
Trial summary
The current study would investigate the effects of a single dose of darolutamide and enzalutamide compared with placebo and compared to each other on human brain blood flow using arterial spin labeling magnetic resonance imaging (ASL-MRI), a non-invasive MRI technique. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cerebrovascular Circulation
- What is being tested?
- Darolutamide (BAY1841788) and Enzalutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 23 Oct 2018to 5 Nov 2019
- 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 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants who are healthy as determined by medical history, physical examination, laboratory tests, and cardiac monitoring.
Who cannot join
- Existing or recent relevant diseases of vital organs (eg, liver diseases, heart diseases, renal disease, lung disease), central nervous system or other organs (eg, Diabetes mellitus, myasthenia gravis).
- Known contraindication to magnetic resonance imaging.
- Any structural variants or pathological abnormalities on structural brain MRI during screening.
- Any history of seizures including a febrile seizure in childhood, loss of consciousness, transient ischemic attack, or any condition that may pre-dispose to seizure.
- Participant with any type of neurological problems or history of psychiatric disorder, especially mood disorders including medical history with suicidal ideation and/or suicide attempts, which may disable the participant to consent to the study.
- Participants who use prescription or oral over the counter medications which might influence the study objectives, dietary/nutritional supplements, (including vitamins, natural and herbal remedies, eg, St. John's wort) within 2 weeks prior to first study intervention administration or during the study.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Centre for Neuroimaging Sciences, King's College
London, SE5 8AF
About this study
Official title: A Phase I, Randomized, Placebo-controlled, Open-label, Three Period Crossover Study to Investigate the Effect of Darolutamide and Enzalutamide on Cerebral Blood Flow in Healthy Male Volunteers.
The current study would investigate the effects of a single dose of darolutamide and enzalutamide compared with placebo and compared to each other on human brain blood flow using arterial spin labeling magnetic resonance imaging (ASL-MRI), a non-invasive MRI technique. The change in cerebral blood flow was an indirect measure of brain penetration.
The risk of drug-associated CNS-related adverse events was likely to be correlated with the concentration of the drug in the brain. In contrast to enzalutamide, preclinical studies of darolutamide indicate that its brain penetration was much lower.
The aim of this study was to determine whether there was a difference between darolutamide and enzalutamide compared to placebo in cerebral blood flow and thus in brain penetration.
Read the detailed description
The primary objective was to investigate drug-induced changes in grey matter cerebral blood flow during single-dose treatment with darolutamide or enzalutamide as compared to placebo using voxel-wise quantification of the grey matter for the entire brain.
The secondary objective was to investigate drug-induced changes in regional cerebral blood flow in brain areas related to cognitive function after single-dose treatment.
- Conditions
- Cerebrovascular Circulation
- Being tested
- Darolutamide (BAY1841788), Enzalutamide, Placebo
- Keywords
- Healthy volunteers, Magnetic Resonance Imaging (MRI)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darolutamide (BAY1841788)Drug
Also called Darolutamide: ODM-201
300 mg tablet darolutamide, once orally
EnzalutamideDrug
Also called MDV3100
4 x 40 mg capsules, once orally
PlaceboOther
Also called Darolutamide-matching placebo
4 placebo tablets, once orally
| Study group | Role | What they receive |
|---|---|---|
| Men_EPD | Experimental | Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide. Receives: Drug: Darolutamide (BAY1841788); Drug: Enzalutamide; Other: Placebo |
| Men_DEP | Experimental | Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo. Receives: Drug: Darolutamide (BAY1841788); Drug: Enzalutamide; Other: Placebo |
| Men_PDE | Experimental | Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide. Receives: Drug: Darolutamide (BAY1841788); Drug: Enzalutamide; Other: Placebo |
| Men_DPE | Experimental | Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide. Receives: Drug: Darolutamide (BAY1841788); Drug: Enzalutamide; Other: Placebo |
| Men_EDP | Experimental | Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo. Receives: Drug: Darolutamide (BAY1841788); Drug: Enzalutamide; Other: Placebo |
| Men_PED | Experimental | Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide. Receives: Drug: Darolutamide (BAY1841788); Drug: Enzalutamide; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in grey-matter cerebral blood flow of enzalutamide as compared to placebo
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of enzalutamide to placebo. Measured in grey matter voxels with arterial spin labeling magnetic resonance imaging (ASL-MRI).
Measured: At 4 hours after drug
Change in grey-matter cerebral blood flow of darolutamide as compared to placebo
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of darolutamide to placebo. Measured in grey matter voxels with ASL-MRI.
Measured: At 4 hours after drug
Change in grey-matter cerebral blood flow of enzalutamide as compared to darolutamide
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of enzalutamide to darolutamide. Measured in grey matter voxels with ASL-MRI.
Measured: At 4 hours after drug
Secondary outcomes (3)
Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to placebo
Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
Measured: At 4 hours after drug
Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of darolutamide as compared to placebo
Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
Measured: At 4 hours after drug
Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to darolutamide
Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
Measured: At 4 hours after drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2018
- Study start23 Oct 2018
- Primary completion1 Oct 2019
- Study completion5 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cerebrovascular CirculationStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03704519
- Sponsor's protocol ID
- 18426
- Other IDs
- 2018-001599-39, 2018
- Status last verified
- Oct 2020
- First submitted
- 10 Oct 2018
- Last updated
- 30 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Williams SCR, Mazibuko N, O'Daly O, Zurth C, Patrick F, Kappeler C, Kuss I, Cole PE. Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial. Target Oncol. 2023 May;18(3):403-413. doi: 10.1007/s11523-023-00959-5. Epub 2023 Apr 27.
PubMed 37103658
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Placebo-controlled, Open-label, Three Period Crossover Study to Investigate the Effect of Darolutamide and Enzalutamide on Cerebral Blood Flow in Healthy Male Volunteers.
- ClinicalTrials.gov ID
- NCT03704519
- Acronym / sponsor ID
- 18426
- Conditions
- Cerebrovascular Circulation
- Keywords
- Healthy volunteers, Magnetic Resonance Imaging (MRI)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 23 Oct 2018 (actual)
- Primary completion
- 1 Oct 2019 (actual)
- Study completion
- 5 Nov 2019 (actual)
- First posted
- 12 Oct 2018 (actual)
- 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.
The current study would investigate the effects of a single dose of darolutamide and enzalutamide compared with placebo and compared to each other on human brain blood flow using arterial spin labeling magnetic resonance imaging (ASL-MRI), a non-invasive MRI technique. The change in cerebral blood flow was an indirect measure of brain penetration.
The risk of drug-associated CNS-related adverse events was likely to be correlated with the concentration of the drug in the brain. In contrast to enzalutamide, preclinical studies of darolutamide indicate that its brain penetration was much lower.
The aim of this study was to determine whether there was a difference between darolutamide and enzalutamide compared to placebo in cerebral blood flow and thus in brain penetration.
Detailed description
The primary objective was to investigate drug-induced changes in grey matter cerebral blood flow during single-dose treatment with darolutamide or enzalutamide as compared to placebo using voxel-wise quantification of the grey matter for the entire brain.
The secondary objective was to investigate drug-induced changes in regional cerebral blood flow in brain areas related to cognitive function after single-dose treatment.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Men_EPD | Experimental | Drug: Darolutamide (BAY1841788), Drug: Enzalutamide, Other: PlaceboHealthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide. |
| Men_DEP | Experimental | Drug: Darolutamide (BAY1841788), Drug: Enzalutamide, Other: PlaceboHealthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo. |
| Men_PDE | Experimental | Drug: Darolutamide (BAY1841788), Drug: Enzalutamide, Other: PlaceboHealthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide. |
| Men_DPE | Experimental | Drug: Darolutamide (BAY1841788), Drug: Enzalutamide, Other: PlaceboHealthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide. |
| Men_EDP | Experimental | Drug: Darolutamide (BAY1841788), Drug: Enzalutamide, Other: PlaceboHealthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo. |
| Men_PED | Experimental | Drug: Darolutamide (BAY1841788), Drug: Enzalutamide, Other: PlaceboHealthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Participants who are healthy as determined by medical history, physical examination, laboratory tests, and cardiac monitoring.
Key exclusion criteria (6 listed)
- Existing or recent relevant diseases of vital organs (eg, liver diseases, heart diseases, renal disease, lung disease), central nervous system or other organs (eg, Diabetes mellitus, myasthenia gravis).
- Known contraindication to magnetic resonance imaging.
- Any structural variants or pathological abnormalities on structural brain MRI during screening.
- Any history of seizures including a febrile seizure in childhood, loss of consciousness, transient ischemic attack, or any condition that may pre-dispose to seizure.
- Participant with any type of neurological problems or history of psychiatric disorder, especially mood disorders including medical history with suicidal ideation and/or suicide attempts, which may disable the participant to consent to the study.
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 |
|---|---|---|
| Darolutamide (BAY1841788)Also: Darolutamide: ODM-201300 mg tablet darolutamide, once orally | Drug | Men_DEP, Men_DPE, Men_EDP, Men_EPD, Men_PDE, Men_PED |
| EnzalutamideAlso: MDV31004 x 40 mg capsules, once orally | Drug | Men_DEP, Men_DPE, Men_EDP, Men_EPD, Men_PDE, Men_PED |
| PlaceboAlso: Darolutamide-matching placebo4 placebo tablets, once orally | Other | Men_DEP, Men_DPE, Men_EDP, Men_EPD, Men_PDE, Men_PED |
Primary outcome
Change in grey-matter cerebral blood flow of enzalutamide as compared to placebo
Time frame: At 4 hours after drug
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of enzalutamide to placebo. Measured in grey matter voxels with arterial spin labeling magnetic resonance imaging (ASL-MRI).
Change in grey-matter cerebral blood flow of darolutamide as compared to placebo
Time frame: At 4 hours after drug
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of darolutamide to placebo. Measured in grey matter voxels with ASL-MRI.
Change in grey-matter cerebral blood flow of enzalutamide as compared to darolutamide
Time frame: At 4 hours after drug
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of enzalutamide to darolutamide. Measured in grey matter voxels with ASL-MRI.
3 secondary outcomes
Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to placebo
Time frame: At 4 hours after drug
Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of darolutamide as compared to placebo
Time frame: At 4 hours after drug
Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to darolutamide
Time frame: At 4 hours after drug
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 30 Oct 2020.
- Derived from this study: PubMed 37103658Williams SCR, Mazibuko N, O'Daly O, Zurth C, Patrick F, Kappeler C, Kuss I, Cole PE. Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial. Target Oncol. 2023 May;18(3):403-413. doi: 10.1007/s11523-023-00959-5. Epub 2023 Apr 27.
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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.
Bayer Study Director study director
Bayer
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 Darolutamide (BAY1841788) and Enzalutamide in people with Cerebrovascular Circulation, run by Bayer at 1 site in United Kingdom.
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 1 inclusion and 6 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 30 Oct 2020. 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 United Kingdom. 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?
Change in grey-matter cerebral blood flow of enzalutamide as compared to placebo (time frame: At 4 hours after drug). 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?
On the ClinicalTrials.gov record for NCT03704519, which also lists 1 linked publication.
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 30 Oct 2020.