Clinical trial NCT03704519: Imaging Study to Compare Effects of Darolutamide and Enzalutamide With Respect to Placebo on the Blood Flow in the Brain in Healthy Male Volunteers.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cerebrovascular Circulation
Keywords: Healthy volunteers
Magnetic Resonance Imaging (MRI)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-10-12
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* Participants who are healthy as determined by medical history, physical examination, laboratory tests, and cardiac monitoring.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in grey-matter cerebral blood flow of enzalutamide as compared to placebo
timeFrame: At 4 hours after drug
measure: Change in grey-matter cerebral blood flow of darolutamide as compared to placebo
timeFrame: At 4 hours after drug
measure: Change in grey-matter cerebral blood flow of enzalutamide as compared to darolutamide
timeFrame: At 4 hours after drug
Secondary outcomes:
measure: Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to placebo
timeFrame: At 4 hours after drug
measure: Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of darolutamide as compared to placebo
timeFrame: At 4 hours after drug
measure: Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to darolutamide
timeFrame: At 4 hours after drug
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Centre for Neuroimaging Sciences, King's College
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: