Study Completed

Cerebrovascular Circulation

Bayer Identifier:

18426

ClinicalTrials.gov Identifier:

NCT03704519

EudraCT Number:

2018-001599-39

EU CT Number:

Not Available

Imaging study to compare effects of darolutamide and enzalutamide with respect to placebo on the blood flow in the brain in healthy male volunteers.

Trial purpose

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.

Key Participants Requirements

Sex

Male

Age

18 - 45 Years

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.

Trial summary

Enrollment Goal

Trial Dates

October 2018 - November 2019

Phase

Phase 1

Could I Receive a placebo

Yes

Products

Nubeqa (Darolutamide, BAY1841788)

Accepts Healthy Volunteer

Yes

Where to participate

Status	Institution	Location
Completed	Centre for Neuroimaging Sciences, King's College	London, SE5 8AF, United Kingdom

Primary Outcome

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).
Time Frame:
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.
Time Frame:
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.
Time Frame:
At 4 hours after drug

Secondary Outcome

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.
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
Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
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
Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
Time Frame:
At 4 hours after drug

Trial design

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.

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Basic Science

Allocation

Randomized

Blinding

N/A

Assignment

Crossover Assignment

Trial Arms

Additional Information

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