Imaging Study to Compare Effects of Darolutamide and Enzalutamide With Respect to Placebo on the Blood Flow in the Brain in Healthy Male Volunteers.

Cerebrovascular Circulation Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03704519
• Other study ID #: 18426
• Secondary ID: 2018-001599-39
• Status: Completed
• Phase: Phase 1
• Start date: October 23, 2018
• Est. completion date: November 5, 2019

Study information

• Verified date: October 2020
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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 information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: November 5, 2019
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cerebrovascular Circulation

Intervention

Drug:
• Darolutamide (BAY1841788)
300 mg tablet darolutamide, once orally
• Enzalutamide
4 x 40 mg capsules, once orally

Other:
• Placebo
4 placebo tablets, once orally

Locations

Country	Name	City	State
United Kingdom	Centre for Neuroimaging Sciences, King's College	London

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	At 4 hours after drug
Primary	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.	At 4 hours after drug
Primary	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.	At 4 hours after drug
Secondary	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.	At 4 hours after drug
Secondary	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.	At 4 hours after drug
Secondary	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.	At 4 hours after drug

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