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

Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT03704519
Collaborator
(none)
26
Enrollment
1
Location
6
Arms
12.4
Actual Duration (Months)
2.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
26 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
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.
Actual Study Start Date :
Oct 23, 2018
Actual Primary Completion Date :
Oct 1, 2019
Actual Study Completion Date :
Nov 5, 2019

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in grey-matter cerebral blood flow of enzalutamide as compared to placebo [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).

    2. Change in grey-matter cerebral blood flow of darolutamide as compared to placebo [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.

    3. Change in grey-matter cerebral blood flow of enzalutamide as compared to darolutamide [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.

    Secondary Outcome Measures

    1. 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]

      Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.

    2. 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]

      Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.

    3. 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]

      Brain areas related to cognitive function comprise hippocampus and frontal cortex. Cerebral blood flow measured with ASL-MRI.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Centre for Neuroimaging Sciences, King's College London United Kingdom SE5 8AF

    Sponsors and Collaborators

    • Bayer

    Investigators

    • Study Director: Bayer Study Director, Bayer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bayer
    ClinicalTrials.gov Identifier:
    NCT03704519
    Other Study ID Numbers:
    • 18426
    • 2018-001599-39
    First Posted:
    Oct 12, 2018
    Last Update Posted:
    Oct 30, 2020
    Last Verified:
    Oct 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bayer
    Healthy volunteers
    Magnetic Resonance Imaging (MRI)

    Study Results

    No Results Posted as of Oct 30, 2020