Imaging Study to Compare Effects of Darolutamide and Enzalutamide With Respect to Placebo on the Blood Flow in the Brain in Healthy Male Volunteers.
- Conditions
- Cerebrovascular Circulation
- Interventions
- Registration Number
- NCT03704519
- Lead Sponsor
- Bayer
- Brief 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. 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 26
- Participants who are healthy as determined by medical history, physical examination, laboratory tests, and cardiac monitoring.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Men_PDE Darolutamide (BAY1841788) Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide. Men_EDP Darolutamide (BAY1841788) Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo. Men_DPE Darolutamide (BAY1841788) Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide. Men_DPE Placebo Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide. Men_EDP Enzalutamide Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo. Men_EPD Darolutamide (BAY1841788) Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide. Men_DEP Placebo Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo. Men_PDE Placebo Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide. Men_EPD Placebo Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide. Men_DEP Darolutamide (BAY1841788) Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo. Men_PED Darolutamide (BAY1841788) Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide. Men_PED Placebo Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide. Men_EDP Placebo Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo. Men_DPE Enzalutamide Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide. Men_EPD Enzalutamide Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide. Men_DEP Enzalutamide Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo. Men_PDE Enzalutamide Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide. Men_PED Enzalutamide Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide.
- Primary Outcome Measures
Name Time Method Change in grey-matter cerebral blood flow of enzalutamide as compared to placebo 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 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 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.
- Secondary Outcome Measures
Name Time Method Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of darolutamide as compared to placebo At 4 hours after drug Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to darolutamide At 4 hours after drug Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to placebo At 4 hours after drug Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
Trial Locations
- Locations (1)
Centre for Neuroimaging Sciences, King's College
🇬🇧London, United Kingdom