Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Effect of a reduced dose on cognitive side effects of enzalutamide in frail (m)CRPC patients

    Summary
    EudraCT number
    		 2018-000779-33
    Trial protocol
    		 NL  
    Global end of trial date
    08 Jan 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Jan 2025
    First version publication date
    04 Jan 2025
    Other versions
    Summary report(s)
    		 Scientific publication

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    UMCN-AKF-18.01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Radboud University Medical Center
    Sponsor organisation address
    Geert Grooteplein 10, Nijmegen, Netherlands, 6525GA
    Public contact
    Department of Pharmacy, Radboud University Medical Center, 0031 243617744, nielka.vanerp@radboudumc.nl
    Scientific contact
    Department of Pharmacy, Radboud University Medical Center, 0031 243617744, nielka.vanerp@radboudumc.nl
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Jan 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Jan 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Jan 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the decrease in the CNS side effect fatigue in frail mCRPC patients treated with a reduced dose of enzalutamide (120mg OD) compared to the standard dose of enzalutamide (160mg OD) after 6 weeks of treatment
    Protection of trial subjects
    In this study the patients are treated with enzalutamide. This drug is licensed, although the intervention group receives a reduced dose. In a phase 1 trial of enzalutamide FDHT PET scans revealed that enzalutamide substantially displaced FDHT binding with a maximum effect seen at 150mg (corresponding with a Ctrough of 11.4 mg/L) was only minimally higher than seen at 60mg (corresponding with a Ctrough of 5.0mg/L)18. This suggests that androgen receptor binding may be saturated at serum levels of ~5.0-11,4 mg/L enzalutamide. Therefore, a minimum trough concentration of 5.0 mg/L could be considered as a target for exposure to enzalutamide. The CV% of the enzalutamide and n-desmethyl concentration is low (≤30%) and the half life is very long (~140h for parent and 180h for active metabolite), therefore the monitoring of plasma concentrations on week 6, month 3 and 6 will prevent patients from being underdosed and consequently suboptimally treated. If a Ctrough concentration of enzalutamide <5.0 mg/L is measured the dose will be increased to standard dose. By starting enzalutamide treatment for frail patients at a reduced dose unnecessary toxicity can be prevented. The potential risk is therefore considered no higher and potentially even lower than with standard patient care. Risk assessment is negligible.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Jun 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 57
    Worldwide total number of subjects
    57
    EEA total number of subjects
    57
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    49
    85 years and over
    8

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 -

    Pre-assignment period milestones
    Number of subjects started
    		 57
    Number of subjects completed
    		 57

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Standard dose
    Arm description
    		 160 mg enzalutamide
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Enzalutamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    160 mg once daily administered as 40 mg tablets

    Arm title
    		 Reduced dose
    Arm description
    		 120 mg enzalutamide
    Arm type
    		 Experimental

    Investigational medicinal product name
    Enzalutamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    120 mg once daily administered as 40 mg tablets

    Number of subjects in period 1
    		Standard dose Reduced dose
    Started
    28
    29
    Completed
    27
    25
    Not completed
    1
    4
         Consent withdrawn by subject
    -
    1
         Physician decision
    -
    1
         Adverse event, non-fatal
    -
    1
         Lack of efficacy
    1
    1

    Baseline characteristics

    		 Close Top of page

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Standard dose
    Reporting group description
    		 160 mg enzalutamide

    Reporting group title
    Reduced dose
    Reporting group description
    		 120 mg enzalutamide

    Primary: Fatigue

    		 Close Top of page
    End point title
    		 Fatigue
    End point description
    Change in score from FACIT-Fatigue questionnaire
    End point type
    Primary
    End point timeframe
    6 weeks versus baseline
    End point values
    		 Standard dose Reduced dose
    Number of subjects analysed
    27 [1]
    26 [2]
    Units: points
        least squares mean (confidence interval 95%)
    -1.1 (-4.2 to 2.0)
    1.1 (-2.2 to 4.3)
    Notes
    [1] - 1 patient discontinued < 6 weeks
    [2] - 3 patients discontinued < 6 weeks
    Statistical analysis title
    		 Primary endpoint fatigue
    Statistical analysis description
    Analyses were performed based on the allocated dose group, regardless of dose modifications during treatment. Linear mixed-effect model analyses were performed to study the differences in side effects over time. Regression coefficients (b) and corresponding 95% confidence intervals (CIs) were presented, indicating the difference in side effects between and within dose groups over time.
    Comparison groups
    Standard dose v Reduced dose
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 6.6

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    SAEs were reported throughout the study period. AEs were monitored according to clinical practice
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    Overall population
    Reporting group description
    		 -

    Serious adverse events
    		 Overall population
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 56 (7.14%)
         number of deaths (all causes)
    4
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Spinal cord injury
    Additional description: due to metastases
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Sepsis
    Additional description: Urosepsis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Overall population
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    31 / 56 (55.36%)
    Nervous system disorders
    Cognitive disturbance
         subjects affected / exposed
    10 / 56 (17.86%)
         occurrences all number
    10
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    31 / 56 (55.36%)
         occurrences all number
    31

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/38485614
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed May 07 17:57:51 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA