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

Bayer

Status and phase: Completed; Phase 1

Conditions: Cerebrovascular Circulation

Treatments: Other: Placebo; Drug: Enzalutamide; Drug: Darolutamide (BAY1841788)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03704519

18426

2018-001599-39 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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 design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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26 participants in 6 patient groups

Men_EPD

Experimental group

Description:

Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide.

Treatment:

Drug: Darolutamide (BAY1841788)

Drug: Enzalutamide

Other: Placebo

Men_DEP

Experimental group

Description:

Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo.

Treatment:

Drug: Darolutamide (BAY1841788)

Drug: Enzalutamide

Other: Placebo

Men_PDE

Experimental group

Description:

Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide.

Treatment:

Drug: Darolutamide (BAY1841788)

Drug: Enzalutamide

Other: Placebo

Men_DPE

Experimental group

Description:

Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide.

Treatment:

Drug: Darolutamide (BAY1841788)

Drug: Enzalutamide

Other: Placebo

Men_EDP

Experimental group

Description:

Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo.

Treatment:

Drug: Darolutamide (BAY1841788)

Drug: Enzalutamide

Other: Placebo

Men_PED

Experimental group

Description:

Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide.

Treatment:

Drug: Darolutamide (BAY1841788)

Drug: Enzalutamide

Other: Placebo