NCT03704519

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
26

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Oct 2018

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 10, 2018

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 12, 2018

Completed
11 days until next milestone

Study Start

First participant enrolled

October 23, 2018

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2019

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

November 5, 2019

Completed
Last Updated

October 30, 2020

Status Verified

October 1, 2020

Enrollment Period

11 months

First QC Date

October 10, 2018

Last Update Submit

October 28, 2020

Conditions

Cerebrovascular Circulation

Keywords

Healthy volunteersMagnetic Resonance Imaging (MRI)

Outcome Measures

Primary Outcomes (3)

  • 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

  • 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

  • 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 Outcomes (3)

  • 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

  • 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

  • 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

Study Arms (6)

Men_EPD

EXPERIMENTAL

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

Drug: Darolutamide (BAY1841788)Drug: EnzalutamideOther: Placebo

Men_DEP

EXPERIMENTAL

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

Drug: Darolutamide (BAY1841788)Drug: EnzalutamideOther: Placebo

Men_PDE

EXPERIMENTAL

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

Drug: Darolutamide (BAY1841788)Drug: EnzalutamideOther: Placebo

Men_DPE

EXPERIMENTAL

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

Drug: Darolutamide (BAY1841788)Drug: EnzalutamideOther: Placebo

Men_EDP

EXPERIMENTAL

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

Drug: Darolutamide (BAY1841788)Drug: EnzalutamideOther: Placebo

Men_PED

EXPERIMENTAL

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

Drug: Darolutamide (BAY1841788)Drug: EnzalutamideOther: Placebo

Interventions

Darolutamide (BAY1841788)DRUG

300 mg tablet darolutamide, once orally

Also known as: Darolutamide: ODM-201
Men_DEPMen_DPEMen_EDPMen_EPDMen_PDEMen_PED
EnzalutamideDRUG

4 x 40 mg capsules, once orally

Also known as: MDV3100
Men_DEPMen_DPEMen_EDPMen_EPDMen_PDEMen_PED
PlaceboOTHER

4 placebo tablets, once orally

Also known as: Darolutamide-matching placebo
Men_DEPMen_DPEMen_EDPMen_EPDMen_PDEMen_PED

Eligibility Criteria

Age18 Years - 45 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre for Neuroimaging Sciences, King's College

London, SE5 8AF, United Kingdom

Location

Related Publications (1)

  • Williams SCR, Mazibuko N, O'Daly O, Zurth C, Patrick F, Kappeler C, Kuss I, Cole PE. Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial. Target Oncol. 2023 May;18(3):403-413. doi: 10.1007/s11523-023-00959-5. Epub 2023 Apr 27.

    PMID: 37103658DERIVED

Related Links

MeSH Terms

Interventions

darolutamideenzalutamide

Study Officials

  • Bayer Study Director

    Bayer

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 10, 2018

First Posted

October 12, 2018

Study Start

October 23, 2018

Primary Completion

October 1, 2019

Study Completion

November 5, 2019

Last Updated

October 30, 2020

Record last verified: 2020-10

Locations

GB(1)