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   43851   clinical trials with a EudraCT protocol, of which   7283   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:
    Effects of Acetyl-DL-Leucine on cerebellar ataxia - a multinational, multicenter, randomized, double-blind, placebo-controlled, 2-way crossover phase III trial (ALCAT)

    Summary
    EudraCT number
    		 2015-000460-34
    Trial protocol
    		 DE   AT  
    Global end of trial date
    07 Jul 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Dec 2022
    First version publication date
    15 Dec 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ALCAT
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    LMU Klinikum
    Sponsor organisation address
    Marchioninistr. 15, Munich, Germany, 81377
    Public contact
    Studienzentrale der Neurologie, LMU Klinikum Munich, 0049 089440076977, IFB-Studienzentrale@med.uni-muenchen.de
    Scientific contact
    Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ), LMU Klinikum Munich, 0049 089440073678, michael.strupp@med.uni-muenchen.de
    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
    29 Jun 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jul 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary aim of the ALCAT trial was to determine the efficacy of a symptomatic treatment with Acetyl-DL-Leucine compared to placebo on absolute change from baseline to week 6 in motor function as assessed by the total score of the Scale for the Assessment and Rating of Ataxia (SARA).
    Protection of trial subjects
    Only standard diagnostic examinations were used during the trial, no experimental examination were performed. Patients received best clinical treatment with continous monitoring of adverse events and side effects including blood tests.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Jan 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 10
    Country: Number of subjects enrolled
    Germany: 98
    Worldwide total number of subjects
    108
    EEA total number of subjects
    108
    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)
    77
    From 65 to 84 years
    31
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 ALCAT was an investigator-initiated, multicenter, double-blind, randomized, placebo-controlled, 2-treatment 2-period crossover phase 3 clinical trial at 7 university centers in Germany (Munich, Bonn, Essen, Tübingen, Berlin) and Austria (Innsbruck). Recruitment occurred between January 25, 2016, and February 17, 2017

    Pre-assignment
    Screening details
    		 Patients were aged at least 18 years and diagnosed with cerebellar ataxia of hereditary (suspected or genetically confirmed) or nonhereditary or unknown type presenting with a total score of at least 3 points on the Scale for the Assessment and Rating of Ataxia (SARA).

    Period 1
    Period 1 title
    First treatment
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo followed by acetyl-DL-leucine (P-A)
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo; subjects took three placebo capsules in the morning; three placebo capsules at noon; and four placebo capsules in the evening in week 3 to 6 (week 1: dose schedule (1-1-1); week 2: dose schedule (2-2-2)).

    Arm title
    		 Acetyl-DL-leucine followed by placebo (A-P)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Acetyl-DL-leucine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Acetyl-DL-Leucine 5 g per day (dose schedule: 3-3-4) in week 3 to 6 after a 2-week up-titration (week 1: 1.5 g per day, dose schedule: 1-1-1; week 2: 3 g per day, dose schedule: 2-2-2). Each capsule contained 500 mg Acetyl-DL-Leucine.

    Number of subjects in period 1
    		Placebo followed by acetyl-DL-leucine (P-A) Acetyl-DL-leucine followed by placebo (A-P)
    Started
    54
    54
    Completed
    52
    50
    Not completed
    2
    4
         Adverse event, non-fatal
    1
    1
         hereditary spastic paraplegia diagnosis
    1
    1
         Lack of efficacy
    -
    2
    Period 2
    Period 2 title
    Washout period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo followed by acetyl-DL-leucine (P-A)
    Arm description
    		 -
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Acetyl-DL-leucine followed by placebo (A-P)
    Arm description
    		 -
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    		Placebo followed by acetyl-DL-leucine (P-A) Acetyl-DL-leucine followed by placebo (A-P)
    Started
    52
    50
    Completed
    50
    49
    Not completed
    2
    1
         Adverse event, non-fatal
    1
    1
         Lost to follow-up
    1
    -
    Period 3
    Period 3 title
    Second treatment
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo followed by acetyl-DL-leucine (P-A)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Acetyl-DL-leucine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Acetyl-DL-Leucine 5 g per day (dose schedule: 3-3-4) in week 3 to 6 after a 2-week up-titration (week 1: 1.5 g per day, dose schedule: 1-1-1; week 2: 3 g per day, dose schedule: 2-2-2). Each capsule contained 500 mg Acetyl-DL-Leucine.

    Arm title
    		 Acetyl-DL-leucine followed by placebo (A-P)
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo; subjects took three placebo capsules in the morning; three placebo capsules at noon; and four placebo capsules in the evening in week 3 to 6 (week 1: dose schedule (1-1-1); week 2: dose schedule (2-2-2)).

    Number of subjects in period 3
    		Placebo followed by acetyl-DL-leucine (P-A) Acetyl-DL-leucine followed by placebo (A-P)
    Started
    50
    49
    Completed
    45
    48
    Not completed
    5
    1
         Adverse event, non-fatal
    4
    -
         Excluded due to Friedreich ataxia diagnosis
    1
    -
         Lack of efficacy
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo followed by acetyl-DL-leucine (P-A)
    Reporting group description
    		 -

    Reporting group title
    Acetyl-DL-leucine followed by placebo (A-P)
    Reporting group description
    		 -

    Reporting group values
    		 Placebo followed by acetyl-DL-leucine (P-A) Acetyl-DL-leucine followed by placebo (A-P) Total
    Number of subjects
    		 54 54 108
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 53 ( 14.3 ) 56.7 ( 14.3 ) -
    Gender categorical
    Units: Subjects
        Female
    		 25 30 55
        Male
    		 29 24 53

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo followed by acetyl-DL-leucine (P-A)
    Reporting group description
    		 -

    Reporting group title
    Acetyl-DL-leucine followed by placebo (A-P)
    Reporting group description
    		 -
    Reporting group title
    Placebo followed by acetyl-DL-leucine (P-A)
    Reporting group description
    		 -

    Reporting group title
    Acetyl-DL-leucine followed by placebo (A-P)
    Reporting group description
    		 -
    Reporting group title
    Placebo followed by acetyl-DL-leucine (P-A)
    Reporting group description
    		 -

    Reporting group title
    Acetyl-DL-leucine followed by placebo (A-P)
    Reporting group description
    		 -

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    105 subjects were Included in the FAS (103 Received placebo treatment, 104 Received acetyl-DL-leucine treatment in the first or the third period; both periods were accounted for in the final analysis). Afterwashout period new baseline was established and all measurements were conducted. 52 In P-A (both time points: 50 for placebo, 41 for acetyl-DL-leucine) 53 In A-P (both time points: 48 for placebo, 49 for acetyl-DL-leucine)

    Primary: Change in SARA total score from baseline to Week 6 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Change in SARA total score from baseline to Week 6 (Acetyl-DL-leucine - placebo) [1]
    End point description
    P value from the mixed model for repeated measures (fixed effects: factor variables for treatment [acetyl-DL-leucine vs placebo], visit and treatment period, and treatment-by-visit interaction; random effects: patient-specific random intercepts). Estimated marginal means (least-squares means) derived from the mixed model, averaged over the levels of period. The mean absolute change from baseline to week 6 in SARA total scores did not differ significantly between acetyl-DL-leucine and placebo (mean treatment difference: 0.23 points [95%CI, −0.40 to 0.85 points]; P = 0.48).
    End point type
    Primary
    End point timeframe
    6 weeks from baseline
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: System limitation - cannot accurately enter the number of participants enrolled in each treatment arm of this cross-over design. Full data set of 105 patients was analyzed of which 103 received placebo and 104 received Acetyl-DL-leucine treatment. The principal model was used to derive (marginal) mean absolute changes in SARA total score from (period-dependent) baseline to posttreatment values, and to compare between both treatment conditions (difference in mean absolute change scores at w6.
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    0.23 (-0.40 to 0.85)
    No statistical analyses for this end point

    Secondary: Change in SCAFI, total z score from baseline to Week 6 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Change in SCAFI, total z score from baseline to Week 6 (Acetyl-DL-leucine - placebo)
    End point description
    Estimated marginal means derived from the mixed model for repeated measures, averaged over the levels of period. Contrast of primary interest: difference means the effect of treatment (mean difference on acetyl-DL-leucine versus placebo) on the efficacy outcome. In SCAFI z score, no treatment benefit of acetyl-DL-leucine compared with placebo could be found. At week 6, the marginal mean treatment difference between acetyl-DL-leucine and placebo in the overall SCAFI score was -0.02 points (95%CI, −0.07 to 0.04 points; P = 0.52) Likewise, we identified a significant period effect, with higher SCAFI z scores in the second period (main effect for mean improvement in index values was 0.12 points [95%CI, 0.06 to 0.17 points; P < 0.001] compared with the first period).
    End point type
    Secondary
    End point timeframe
    6 weeks from baseline
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    -0.02 (-0.07 to 0.04)
    No statistical analyses for this end point

    Secondary: Change in EQ VAS score from baseline to Week 6 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Change in EQ VAS score from baseline to Week 6 (Acetyl-DL-leucine - placebo)
    End point description
    Estimated marginal means derived from the mixed model for repeated measures, averaged over the levels of period. Contrast of primary interest: difference means the effect of treatment (mean difference on acetyl-DL-leucine versus placebo) on the efficacy outcome. There was no evidence for a clinically relevant effect of acetyl-DL-leucine on the subjective health rating EQ visual analogue scale compared with placebo at week 6 with no evidence of a period effect. At week 6, the marginal mean treatment difference between acetyl-DL-leucine and placebo in the overall self-rated health status was −1.84 points (95%CI, −5.19 to 1.50 points; P = 0.28)
    End point type
    Secondary
    End point timeframe
    6 weeks from baseline
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    -1.84 (-5.19 to 1.50)
    No statistical analyses for this end point

    Secondary: Change in BDI-II, sum score from baseline to Week 6 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Change in BDI-II, sum score from baseline to Week 6 (Acetyl-DL-leucine - placebo)
    End point description
    Estimated marginal means derived from the mixed model for repeated measures, averaged over the levels of period. Contrast of primary interest: difference means the effect of treatment (mean difference on acetyl-DL-leucine versus placebo) on the efficacy outcome. At week 6, the marginal mean treatment difference between acetyl-DL-leucine and placebo in the BDI-II sum score was 0.10 points (95%CI, -0.91 to 1.11 points; P = 0.85) Higher BDI scores (range 0 to 63) indicate greater impairment.
    End point type
    Secondary
    End point timeframe
    6 weeks from baseline
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    0.10 (-0.91 to 1.11)
    No statistical analyses for this end point

    Secondary: Change in FSS, mean score from baseline to Week 6 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Change in FSS, mean score from baseline to Week 6 (Acetyl-DL-leucine - placebo)
    End point description
    Estimated marginal means derived from the mixed model for repeated measures, averaged over the levels of period. Contrast of primary interest: difference means the effect of treatment (mean difference on acetyl-DL-leucine versus placebo) on the efficacy outcome. At week 6, the marginal mean treatment difference between acetyl-DL-leucine and placebo in the FSS mean score was 0.06 points (95%CI, -0.17 to 0.30 points; P = 0.61) Higher FSS scores (range 1 to 7) indicate greater impairment.
    End point type
    Secondary
    End point timeframe
    6 weeks from baseline
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    0.06 (-0.17 to 0.30)
    No statistical analyses for this end point

    Secondary: Changes in SARA total score from baseline to Week 2 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Changes in SARA total score from baseline to Week 2 (Acetyl-DL-leucine - placebo)
    End point description
    Contrast of primary interest: difference is the effect of treatment (acetyl-DL-leucine versus placebo) on the efficacy outcome. At week 2, the marginal mean treatment difference in SARA total scores did not differ significantly between acetyl-DL-leucine and placebo (mean treatment difference: 0.43 points [95%CI, −0.18 to 1.05 points]; P = 0.17).
    End point type
    Secondary
    End point timeframe
    2 weeks from baseline
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    0.43 (-0.18 to 1.05)
    No statistical analyses for this end point

    Secondary: Changes in SCAFI total z score from baseline to Week 2 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Changes in SCAFI total z score from baseline to Week 2 (Acetyl-DL-leucine - placebo)
    End point description
    Estimated marginal means derived from the mixed model for repeated measures, averaged over the levels of period. Contrast of primary interest: difference means the effect of treatment (mean difference on acetyl-DL-leucine versus placebo) on the efficacy outcome. In SCAFI z score, no treatment benefit of acetyl-DL-leucine compared with placebo could be found. At week 6, the marginal mean treatment difference between acetyl-DL-leucine and placebo in the overall SCAFI score was 0.03 points (95%CI, −0.02 to 0.08 points; P = 0.26)
    End point type
    Secondary
    End point timeframe
    2 weeks from baseline
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    0.03 (-0.02 to 0.08)
    No statistical analyses for this end point

    Secondary: Changes in EQ VAS score from baseline to Week 2 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Changes in EQ VAS score from baseline to Week 2 (Acetyl-DL-leucine - placebo)
    End point description
    Estimated marginal means derived from the mixed model for repeated measures, averaged over the levels of period. Contrast of primary interest: difference means the effect of treatment (mean difference on acetyl-DL-leucine versus placebo) on the efficacy outcome. There was no evidence for a clinically relevant effect of acetyl-DL-leucine on the subjective health rating EQ visual analogue scale compared with placebo at week 6 with no evidence of a period effect. At week 2, the marginal mean treatment difference between acetyl-DL-leucine and placebo in the overall self-rated health status was 0.78 points (95%CI, −2.51 to 4.07 points; P = 0.64)
    End point type
    Secondary
    End point timeframe
    2 weeks from baseline
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    0.78 (-2.51 to 4.07)
    No statistical analyses for this end point

    Secondary: Change in BDI-II, sum score from baseline to Week 2 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Change in BDI-II, sum score from baseline to Week 2 (Acetyl-DL-leucine - placebo)
    End point description
    Estimated marginal means derived from the mixed model for repeated measures, averaged over the levels of period. Contrast of primary interest: difference means the effect of treatment (mean difference on acetyl-DL-leucine versus placebo) on the efficacy outcome. At week 6, the marginal mean treatment difference between acetyl-DL-leucine and placebo in the BDI-II sum score was 0.49 points (95%CI, -0.50 to 1.48 points; P = 0.33). Higher BDI scores (range 0 to 63) indicate greater impairment.
    End point type
    Secondary
    End point timeframe
    2 weeks from baseline
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    0.49 (-0.50 to 1.48)
    No statistical analyses for this end point

    Secondary: Change in FSS, mean score from baseline to Week 2 (Acetyl-DL-leucine - placebo)

    		 Close Top of page
    End point title
    		 Change in FSS, mean score from baseline to Week 2 (Acetyl-DL-leucine - placebo)
    End point description
    Estimated marginal means derived from the mixed model for repeated measures, averaged over the levels of period. Contrast of primary interest: difference means the effect of treatment (mean difference on acetyl-DL-leucine versus placebo) on the efficacy outcome. At week 6, the marginal mean treatment difference between acetyl-DL-leucine and placebo in the FSS mean score was 0.09 points (95%CI, -0.15 to 0.32 points; P = 0.47). Higher FSS scores (range 1 to 7) indicate greater impairment.
    End point type
    Secondary
    End point timeframe
    2 weeks from baseline
    End point values
    		 Full Analysis Set
    Number of subjects analysed
    105
    Units: points
        least squares mean (confidence interval 95%)
    0.09 (-0.15 to 0.32)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Documentation and evaluation of each AE occurred between the start with first study specific intervention up to 30 days after the subject has received the last dose of trial drug.
    Adverse event reporting additional description
    A total of 246 AEs (86 patients with at least 1 AE) occurred in similar numbers in both sequence groups (A-P: 42 patients; P-A: 45 patients) with a median of 2 (range 0-10) AEs per patient throughout their individual observation period. Of these 8 were assessed as SAEs (6 on acetyl-DLleucine, 2 on placebo), whereas 191 were mild and 48 moderate.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21
    Reporting groups
    Reporting group title
    Placebo followed by Acetyl-DL-leucin
    Reporting group description
    		 Patients were initially screened and assessed for eligibility at the first visit and randomized at the second to 1 of 2 treatment sequences and after the washout period they were given the alternatie therapy. In this group the first therapy they received was placebo and was followed by active treatment [P-A].

    Reporting group title
    Acetyl-DL-leucin followed by placebo
    Reporting group description
    		 Patients were initially screened and assessed for eligibility at the first visit and randomized at the second to 1 of 2 treatment sequences and after the washout period they were given the alternatie therapy. In this group the first therapy they received was Acetyl-DL-leucine and was followed by placebo treatment [A-P].

    Serious adverse events
    		 Placebo followed by Acetyl-DL-leucin Acetyl-DL-leucin followed by placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 103 (5.83%)
    2 / 104 (1.92%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    2 / 103 (1.94%)
    0 / 104 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischemic stroke
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Active suicidal ideation
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient global amnesia
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin texture abnormal
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 4%
    Non-serious adverse events
    		 Placebo followed by Acetyl-DL-leucin Acetyl-DL-leucin followed by placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    59 / 103 (57.28%)
    52 / 104 (50.00%)
    Injury, poisoning and procedural complications
    Bruise from the fall
         subjects affected / exposed
    1 / 103 (0.97%)
    2 / 104 (1.92%)
         occurrences all number
    1
    2
    Cut
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Injury
         subjects affected / exposed
    4 / 103 (3.88%)
    3 / 104 (2.88%)
         occurrences all number
    4
    3
    Nervous system disorders
    Additive behavior to study medication
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Concentration disturbance
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 104 (0.96%)
         occurrences all number
    1
    1
    Inner restlessness
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Parkinson's disease worsening
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    2
    0
    Ataxia worsening
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 104 (0.96%)
         occurrences all number
    1
    1
    Vertigo
         subjects affected / exposed
    2 / 103 (1.94%)
    0 / 104 (0.00%)
         occurrences all number
    2
    0
    Mixed anxiety-panic disorder
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Ischias
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Deterioration of gait
         subjects affected / exposed
    0 / 103 (0.00%)
    3 / 104 (2.88%)
         occurrences all number
    0
    3
    Increase in pre-existing depressive moods
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Tingling paresthesias left hand, distally accentuated
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 103 (3.88%)
    3 / 104 (2.88%)
         occurrences all number
    5
    3
    Chills
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Daytime sleepiness
         subjects affected / exposed
    2 / 103 (1.94%)
    1 / 104 (0.96%)
         occurrences all number
    2
    1
    Deterioration of hand motor skills/coordination
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 104 (0.96%)
         occurrences all number
    1
    1
    Difficulty falling asleep
         subjects affected / exposed
    2 / 103 (1.94%)
    0 / 104 (0.00%)
         occurrences all number
    2
    0
    Sleep disorder
         subjects affected / exposed
    3 / 103 (2.91%)
    0 / 104 (0.00%)
         occurrences all number
    3
    0
    Dizziness/increase of dizziness
         subjects affected / exposed
    5 / 103 (4.85%)
    5 / 104 (4.81%)
         occurrences all number
    8
    6
    Fall
         subjects affected / exposed
    8 / 103 (7.77%)
    11 / 104 (10.58%)
         occurrences all number
    12
    13
    Headache/Migraine
         subjects affected / exposed
    4 / 103 (3.88%)
    7 / 104 (6.73%)
         occurrences all number
    5
    9
    Increased instability
         subjects affected / exposed
    2 / 103 (1.94%)
    1 / 104 (0.96%)
         occurrences all number
    2
    1
    Increased staggering
         subjects affected / exposed
    3 / 103 (2.91%)
    0 / 104 (0.00%)
         occurrences all number
    3
    0
    Speech disorder
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 104 (0.96%)
         occurrences all number
    1
    1
    Sensory disturbance increase
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Pain in extremity
         subjects affected / exposed
    7 / 103 (6.80%)
    4 / 104 (3.85%)
         occurrences all number
    7
    4
    Numbness
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Uncontrolled sallivation
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Disturbances of neck muscles after a BOTOX inje
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Increased clumsiness after the up-titration of the study medication
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Nocturia
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Stabbing chest/breast pain
         subjects affected / exposed
    0 / 103 (0.00%)
    2 / 104 (1.92%)
         occurrences all number
    0
    2
    Thick feet without water retention
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Worsening of restless leg syndrome
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    General malaise after taking tablets
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Bilateral hearing aid device supply
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Preexisting mild tinnitus on right side increased significantly
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Eye disorders
    Increase in double vision
         subjects affected / exposed
    0 / 103 (0.00%)
    3 / 104 (2.88%)
         occurrences all number
    0
    3
    Gastrointestinal disorders
    Bowel movements drier and harder
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    1 / 103 (0.97%)
    2 / 104 (1.92%)
         occurrences all number
    1
    2
    Diarrhoea
         subjects affected / exposed
    5 / 103 (4.85%)
    7 / 104 (6.73%)
         occurrences all number
    6
    9
    Dyspepsia
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Reflux gastritis
         subjects affected / exposed
    5 / 103 (4.85%)
    1 / 104 (0.96%)
         occurrences all number
    5
    1
    Stomach ache
         subjects affected / exposed
    2 / 103 (1.94%)
    4 / 104 (3.85%)
         occurrences all number
    3
    5
    Nausea
         subjects affected / exposed
    2 / 103 (1.94%)
    3 / 104 (2.88%)
         occurrences all number
    3
    4
    Vomiting
         subjects affected / exposed
    1 / 103 (0.97%)
    5 / 104 (4.81%)
         occurrences all number
    1
    5
    Weight decreased
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Flatulence
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Persistent morning sickness
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Rhinitis allergic
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    2 / 103 (1.94%)
    1 / 104 (0.96%)
         occurrences all number
    2
    1
    Influenza
         subjects affected / exposed
    4 / 103 (3.88%)
    1 / 104 (0.96%)
         occurrences all number
    4
    1
    Sore throat
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Laryngitis
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 104 (0.96%)
         occurrences all number
    1
    1
    Cough
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Psoriasis worsening
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Eczema
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 103 (0.00%)
    4 / 104 (3.85%)
         occurrences all number
    0
    6
    Renal and urinary disorders
    Cystitis
         subjects affected / exposed
    2 / 103 (1.94%)
    0 / 104 (0.00%)
         occurrences all number
    2
    0
    Urinary urge increase
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 104 (0.96%)
         occurrences all number
    1
    1
    Renal pain
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    5 / 103 (4.85%)
    2 / 104 (1.92%)
         occurrences all number
    5
    2
    Blockage in hip joint with limitation of movement and pain
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Lumbago
         subjects affected / exposed
    2 / 103 (1.94%)
    1 / 104 (0.96%)
         occurrences all number
    2
    1
    Muscle soreness
         subjects affected / exposed
    2 / 103 (1.94%)
    0 / 104 (0.00%)
         occurrences all number
    3
    0
    Muscle spasms
         subjects affected / exposed
    0 / 103 (0.00%)
    5 / 104 (4.81%)
         occurrences all number
    0
    5
    Jaw blockage with toothache
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Spontaneous cramps in the cave
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 103 (5.83%)
    5 / 104 (4.81%)
         occurrences all number
    6
    5
    Herpes labialis infection after a cold
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Tooth inflammation
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 104 (0.96%)
         occurrences all number
    1
    1
    Suspected sinusitis
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Hyperlipidaemia
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Weight increased
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 104 (0.00%)
         occurrences all number
    1
    0
    Anorexia nervosa
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 104 (0.96%)
         occurrences all number
    0
    1

    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/34905009
    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-Sat Apr 20 06:23:24 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA