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

October 28, 2020 updated by: Bayer

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SE5 8AF
        • Centre for Neuroimaging Sciences, King's College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Men_EPD
Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide.
Drug: Darolutamide (BAY1841788)
300 mg tablet darolutamide, once orally
Other Names:
  • Darolutamide: ODM-201
Drug: Enzalutamide
4 x 40 mg capsules, once orally
Other Names:
  • MDV3100
Other: Placebo
4 placebo tablets, once orally
Other Names:
  • Darolutamide-matching placebo
Experimental: Men_DEP
Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo.
Drug: Darolutamide (BAY1841788)
300 mg tablet darolutamide, once orally
Other Names:
  • Darolutamide: ODM-201
Drug: Enzalutamide
4 x 40 mg capsules, once orally
Other Names:
  • MDV3100
Other: Placebo
4 placebo tablets, once orally
Other Names:
  • Darolutamide-matching placebo
Experimental: Men_PDE
Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide.
Drug: Darolutamide (BAY1841788)
300 mg tablet darolutamide, once orally
Other Names:
  • Darolutamide: ODM-201
Drug: Enzalutamide
4 x 40 mg capsules, once orally
Other Names:
  • MDV3100
Other: Placebo
4 placebo tablets, once orally
Other Names:
  • Darolutamide-matching placebo
Experimental: Men_DPE
Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide.
Drug: Darolutamide (BAY1841788)
300 mg tablet darolutamide, once orally
Other Names:
  • Darolutamide: ODM-201
Drug: Enzalutamide
4 x 40 mg capsules, once orally
Other Names:
  • MDV3100
Other: Placebo
4 placebo tablets, once orally
Other Names:
  • Darolutamide-matching placebo
Experimental: Men_EDP
Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo.
Drug: Darolutamide (BAY1841788)
300 mg tablet darolutamide, once orally
Other Names:
  • Darolutamide: ODM-201
Drug: Enzalutamide
4 x 40 mg capsules, once orally
Other Names:
  • MDV3100
Other: Placebo
4 placebo tablets, once orally
Other Names:
  • Darolutamide-matching placebo
Experimental: Men_PED
Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide.
Drug: Darolutamide (BAY1841788)
300 mg tablet darolutamide, once orally
Other Names:
  • Darolutamide: ODM-201
Drug: Enzalutamide
4 x 40 mg capsules, once orally
Other Names:
  • MDV3100
Other: Placebo
4 placebo tablets, once orally
Other Names:
  • Darolutamide-matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in grey-matter cerebral blood flow of enzalutamide as compared to placebo
Time Frame: At 4 hours after drug
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
Time Frame: At 4 hours after drug
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
Time Frame: At 4 hours after drug
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to placebo
Time Frame: At 4 hours after drug
Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
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
Time Frame: At 4 hours after drug
Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
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
Time Frame: At 4 hours after drug
Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.
At 4 hours after drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2018

Primary Completion (Actual)

October 1, 2019

Study Completion (Actual)

November 5, 2019

Study Registration Dates

First Submitted

October 10, 2018

First Submitted That Met QC Criteria

October 10, 2018

First Posted (Actual)

October 12, 2018

Study Record Updates

Last Update Posted (Actual)

October 30, 2020

Last Update Submitted That Met QC Criteria

October 28, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 18426
  • 2018-001599-39 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cerebrovascular Circulation

Clinical Trials on Darolutamide (BAY1841788)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Suriname

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe