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:
    Effects of ODM-109 on respiratory function in patients with ALS. A randomised, double blind, placebo-controlled, cross-over, 3-period, multicentre study with open-label follow-up extension

    Summary
    EudraCT number
    		 2014-004567-21
    Trial protocol
    		 IE   DE   GB   NL  
    Global end of trial date
    11 May 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 May 2018
    First version publication date
    25 May 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    3119001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02487407
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Orion Pharma
    Sponsor organisation address
    Orionintie 1, Espoo, Finland, 02200
    Public contact
    Clinical Trials Information, Orion Corporation Orion Pharma, 358 0104261, clinicaltrials@orionpharma.com
    Scientific contact
    Clinical Trials Information, Orion Corporation Orion Pharma, 358 0104261, clinicaltrials@orionpharma.com
    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
    11 May 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 May 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    11 May 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to investigate the efficacy of oral levosimendan on respiratory function in patients with Amyotrophic Lateral Sclerosis.
    Protection of trial subjects
    The study data was monitored regularly by the Sponsor, and accumulating data were reviewed periodically by an independent Data and Safety Monitoring Board (DSMB). The DSMB were able to amend the study protocol for safety reasons, stop the study or withdraw individual patients from treatment if deemed necessary. The study included frequent assessment of safety measurements typical of clinical trials, including blood pressure, heart rate 12-lead ECG, 24 hour Holter (ECG) recording, safety laboratory tests and adverse events. These were performed before, during and after study drug treatment Specific criteria were in place for the withdrawal of patients from study treatment, including increased heart rate (increased >15 bpm from baseline), ventricular tachycardia, atrial fibrillation/flutter, pregnancy and need for invasive ventilator support. The investigator could also withdraw the treatment if considered to be in the best interests of the subject. Patients were free to leave the study at any time but were also withdrawn in the event of a safety finding of clinical concern.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Jul 2015
    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
    Netherlands: 5
    Country: Number of subjects enrolled
    United Kingdom: 25
    Country: Number of subjects enrolled
    Germany: 33
    Country: Number of subjects enrolled
    Ireland: 3
    Worldwide total number of subjects
    66
    EEA total number of subjects
    66
    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)
    50
    From 65 to 84 years
    16
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients with amyotrophic lateral sclerosis (ALS) were recruited.

    Pre-assignment
    Screening details
    		 Male or female subjects, disease duration from symptom onset 12-48 months before the baseline, written informed consent (IC) obtained. Age at least 18 years, upright slow vital capacity (SVC) between 60-90% of the predicted value for age, height and sex at screening visit, mormal oxygen saturation during daytime, using riluzole.

    Period 1
    Period 1 title
    Cross-over part
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    Exactly similar placebo capsules were used, and 1 placebo capsule was given in the evening for the 1 mg treatment group.

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Levosimendan 1 mg
    Arm description
    		 1 levosimendan 1 mg capsule in the morning and 1 placebo capsule 12 hours later for 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Levosimendan 1 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 levosimendan 1 mg capsule in the morning for 14 days.

    Arm title
    		 Levosimendan 2 mg
    Arm description
    		 1 levosimendan 1 mg capsule in the morning and 1 mg capsule 12 hours later for 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Levosimendan 1 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 levosimendan 1 mg capsule in the morning and 1 mg capsule 12 hours later for 14 days.

    Arm title
    		 Placebo
    Arm description
    		 1 placebo capsule in the morning and 1 placebo capsule 12 hours later.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo levosimendan capsule
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo levosimendan capsule containing only excipients.

    Number of subjects in period 1
    		Levosimendan 1 mg Levosimendan 2 mg Placebo
    Started
    66
    66
    66
    Completed
    50
    50
    50
    Not completed
    16
    16
    16
         Adverse event, serious fatal
    1
    1
    1
         Adverse event, non-fatal
    7
    7
    7
         Personal reason
    3
    3
    3
         Other
    3
    3
    3
         Adverse event, serious, non-fatal
    2
    2
    2
    Period 2
    Period 2 title
    Open label extension
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Opel label extension
    Arm description
    		 Levosimendan treatment 1-2 mg was continued for 6 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Levosimendan 1 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg dose of levosimendan in the morning for 2 weeks. Then the dose was increased to 1 mg b.i.d., if the 1 mg once a day dosing was well tolerated.

    Number of subjects in period 2
    		Opel label extension
    Started
    50
    Completed
    35
    Not completed
    15
         Adverse event, serious fatal
    4
         Adverse event, non-fatal
    5
         Personal reason
    1
         Other
    2
         Adverse event, serious, non-fatal
    2
         Protocol deviation
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cross-over part
    Reporting group description
    		 -

    Reporting group values
    		 Cross-over part Total
    Number of subjects
    		 66 66
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 50 50
        Adults 65-84 years
    		 16 16
    Gender categorical
    Units: Subjects
        Female
    		 19 19
        Male
    		 47 47

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Levosimendan 1 mg
    Reporting group description
    		 1 levosimendan 1 mg capsule in the morning and 1 placebo capsule 12 hours later for 14 days.

    Reporting group title
    Levosimendan 2 mg
    Reporting group description
    		 1 levosimendan 1 mg capsule in the morning and 1 mg capsule 12 hours later for 14 days.

    Reporting group title
    Placebo
    Reporting group description
    		 1 placebo capsule in the morning and 1 placebo capsule 12 hours later.
    Reporting group title
    Opel label extension
    Reporting group description
    		 Levosimendan treatment 1-2 mg was continued for 6 months.

    Primary: SVC (sitting)

    		 Close Top of page
    End point title
    		 SVC (sitting)
    End point description
    The primary efficacy endpoint was SVC assessed in sitting position (% predicted for age, height and sex), defined as change from baseline at day 14 predose assessment.
    End point type
    Primary
    End point timeframe
    Pre-dose on day 14
    End point values
    		 Levosimendan 1 mg Levosimendan 2 mg Placebo
    Number of subjects analysed
    59
    59
    58
    Units: percent
        arithmetic mean (standard deviation)
    -2.8 ( 8.9 )
    -1.9 ( 8.1 )
    -1.8 ( 7.3 )
    Statistical analysis title
    		 Change from baseline, SVC (sitting)
    Statistical analysis description
    Analysis of covariance
    Comparison groups
    Levosimendan 1 mg v Placebo
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.67
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 Change from baseline, SVC (sitting)
    Statistical analysis description
    Analysis of covariance
    Comparison groups
    Levosimendan 2 mg v Placebo
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.98
    Method
    		 ANCOVA
    Confidence interval

    Post-hoc: SVC (sitting, post-hoc)

    		 Close Top of page
    End point title
    		 SVC (sitting, post-hoc)
    End point description
    Due to significant period effect, changes from period-wise baselines (period 1 day 1, period 2 day 1 and period 3 day 1, respectively) were considered as primary comparisons (post-hoc).
    End point type
    Post-hoc
    End point timeframe
    Pre-dose on day 14
    End point values
    		 Levosimendan 1 mg Levosimendan 2 mg Placebo
    Number of subjects analysed
    59
    59
    58
    Units: percent
        arithmetic mean (standard deviation)
    -0.8 ( 7.1 )
    0.2 ( 7.3 )
    -0.7 ( 6.0 )
    Statistical analysis title
    		 Change from baseline SVC (sitting, post-hoc)
    Comparison groups
    Levosimendan 1 mg v Placebo
    Number of subjects included in analysis
    117
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.97
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 Change from baseline SVC (sitting, post-hoc)
    Comparison groups
    Levosimendan 2 mg v Placebo
    Number of subjects included in analysis
    117
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.85
    Method
    		 ANCOVA
    Confidence interval

    Post-hoc: SVC (supine, post-hoc)

    		 Close Top of page
    End point title
    		 SVC (supine, post-hoc)
    End point description
    Due to significant period effect, changes from period-wise baselines (period 1 day 1, period 2 day 1 and period 3 day 1, respectively) were considered as primary comparisons (post-hoc).
    End point type
    Post-hoc
    End point timeframe
    Pre-dose day 14
    End point values
    		 Levosimendan 1 mg Levosimendan 2 mg Placebo
    Number of subjects analysed
    59
    58
    56
    Units: percent
        arithmetic mean (standard deviation)
    1.0 ( 8.6 )
    2.7 ( 8.3 )
    -4.0 ( 9.4 )
    Statistical analysis title
    		 Change from baseline SVC (supine, post-hoc)
    Comparison groups
    Levosimendan 1 mg v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.018
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 Change from baseline SVC (supine, post-hoc)
    Comparison groups
    Levosimendan 2 mg v Placebo
    Number of subjects included in analysis
    114
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    AEs were assessed from signing the informed consent until the end-of study visit. The duration of the study was about 13-14 weeks for the double-blind crossover part, and about 9-10 months for the entire study, including the 6 months open-label follow-up.
    Adverse event reporting additional description
    Non-serious adverse events are reported, if the frequency in cross-over part was >/= 3 subjects, appr. 5 %.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19
    Reporting groups
    Reporting group title
    Levosimendan 1 mg
    Reporting group description
    		 1 levosimendan 1 mg capsule in the morning and 1 placebo capsule 12 hours later for 14 days.

    Reporting group title
    Levosimendan 2 mg
    Reporting group description
    		 1 levosimendan 1 mg capsule in the morning and 1 mg capsule 12 hours later for 14 days.

    Reporting group title
    Placebo
    Reporting group description
    		 1 placebo capsule in the morning and 1 placebo capsule 12 hours later.

    Reporting group title
    Open label extension
    Reporting group description
    		 Levosimendan treatment 1-2 mg daily continued for 6 months

    Serious adverse events
    		 Levosimendan 1 mg Levosimendan 2 mg Placebo Open label extension
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 59 (8.47%)
    3 / 59 (5.08%)
    6 / 58 (10.34%)
    31 / 50 (62.00%)
         number of deaths (all causes)
    1
    0
    0
    4
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Craniocerebral injury
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 58 (1.72%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 58 (1.72%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 58 (1.72%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Femoral neck fracture
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Amyotrophic lateral sclerosis
         subjects affected / exposed
    2 / 59 (3.39%)
    0 / 59 (0.00%)
    1 / 58 (1.72%)
    2 / 50 (4.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    6 / 50 (12.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic cyst
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 59 (1.69%)
    0 / 58 (0.00%)
    6 / 50 (12.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Hypoventilation
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    2 / 50 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nocturnal dyspnoea
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    2 / 50 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Panic attack
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 58 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 58 (1.72%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Levosimendan 1 mg Levosimendan 2 mg Placebo Open label extension
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    42 / 59 (71.19%)
    50 / 59 (84.75%)
    31 / 58 (53.45%)
    42 / 50 (84.00%)
    Investigations
    Heart rate increased
         subjects affected / exposed
    1 / 59 (1.69%)
    5 / 59 (8.47%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    1
    5
    0
    1
    Oxygen saturation decreased
         subjects affected / exposed
    3 / 59 (5.08%)
    4 / 59 (6.78%)
    0 / 58 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    3
    5
    0
    1
    Blood glucose increased
         subjects affected / exposed
    1 / 59 (1.69%)
    3 / 59 (5.08%)
    0 / 58 (0.00%)
    0 / 50 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    9 / 59 (15.25%)
    9 / 59 (15.25%)
    5 / 58 (8.62%)
    14 / 50 (28.00%)
         occurrences all number
    12
    10
    7
    23
    Skin abrasion
         subjects affected / exposed
    3 / 59 (5.08%)
    0 / 59 (0.00%)
    1 / 58 (1.72%)
    4 / 50 (8.00%)
         occurrences all number
    3
    0
    3
    1
    Contusion
         subjects affected / exposed
    2 / 59 (3.39%)
    3 / 59 (5.08%)
    1 / 58 (1.72%)
    0 / 50 (0.00%)
         occurrences all number
    2
    3
    2
    0
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    1 / 59 (1.69%)
    4 / 59 (6.78%)
    0 / 58 (0.00%)
    5 / 50 (10.00%)
         occurrences all number
    1
    4
    0
    10
    Tachycardia
         subjects affected / exposed
    2 / 59 (3.39%)
    2 / 59 (3.39%)
    1 / 58 (1.72%)
    0 / 50 (0.00%)
         occurrences all number
    2
    2
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    10 / 59 (16.95%)
    17 / 59 (28.81%)
    2 / 58 (3.45%)
    5 / 50 (10.00%)
         occurrences all number
    10
    17
    2
    6
    Dizziness
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 59 (5.08%)
    1 / 58 (1.72%)
    1 / 50 (2.00%)
         occurrences all number
    0
    3
    1
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    4 / 59 (6.78%)
    1 / 59 (1.69%)
    1 / 58 (1.72%)
    3 / 50 (6.00%)
         occurrences all number
    4
    1
    1
    3
    Diarrhoea
         subjects affected / exposed
    1 / 59 (1.69%)
    3 / 59 (5.08%)
    2 / 58 (3.45%)
    3 / 50 (6.00%)
         occurrences all number
    1
    3
    2
    3
    Constipation
         subjects affected / exposed
    2 / 59 (3.39%)
    2 / 59 (3.39%)
    3 / 58 (5.17%)
    1 / 50 (2.00%)
         occurrences all number
    2
    2
    3
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 59 (1.69%)
    2 / 59 (3.39%)
    1 / 58 (1.72%)
    2 / 50 (4.00%)
         occurrences all number
    1
    2
    1
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 59 (10.17%)
    0 / 59 (0.00%)
    1 / 58 (1.72%)
    3 / 50 (6.00%)
         occurrences all number
    6
    0
    1
    3
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 59 (3.39%)
    1 / 59 (1.69%)
    0 / 58 (0.00%)
    3 / 50 (6.00%)
         occurrences all number
    2
    1
    0
    4
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    1 / 59 (1.69%)
    2 / 59 (3.39%)
    0 / 58 (0.00%)
    0 / 50 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    3 / 58 (5.17%)
    2 / 50 (4.00%)
         occurrences all number
    0
    0
    3
    2
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 59 (6.78%)
    4 / 59 (6.78%)
    3 / 58 (5.17%)
    4 / 50 (8.00%)
         occurrences all number
    4
    4
    3
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Apr 2015
    Amendment 1.0. UK only. Addition and update to patient withdrawal criteria as requested by the UK CA. Superseded by Amendment 4.0
    05 Jun 2015
    Amendment 2.0. NL only. Addition and update to patient withdrawal criteria as requested by the UK CA. Superseded by Amendment 4.0.
    16 Jul 2015
    Amendment 3.0 Version 1.0. DE only. Superseded by Amendment 5. IC text updated. Acceptable forms of contraception added.
    29 Oct 2015
    Amendment 4.0. Version 1.0. Final protocol in countries listed: UK, NL only. • IC text updated • Subjects not taking riluzole allowed to enter the study • Changes to entry criteria to make them clinically more precise/adequate without affecting the scientific integrity of the study • Use of EMG in the diagnosis of ALS clarified
    29 Oct 2015
    Amendment 5.0 Version 1.0. Superseded by Amendment 5 Version 2. DE only. Inclusion of a DSMB for the study.
    05 Jan 2016
    Amendment 6.0 version 1.0 Not accepted by CA Superseded by AM6 version 2.0. IRE only. • IC text updated • Subjects not taking riluzole allowed to enter the study • Changes to entry criteria to make them clinically more precise/adequate without affecting the scientific integrity of the study • Use of EMG in the diagnosis of ALS clarified
    04 Mar 2016
    Amendment 6.0 version 2.0 Final protocol. IRE only. Update to study stopping rules regarding ventricular tachycardia.
    22 Apr 2016
    Amendment 5.0, Version 2.0 Final protocol. DE only. • IC text updated • Subjects not taking riluzole allowed to enter the study • Changes to entry criteria to make them clinically more precise/adequate without affecting the scientific integrity of the study • Use of EMG in the diagnosis of ALS clarified • Access to post study levosimendan updated • Order of assessment for respiratory and grip strength updated to be provided as separate instructions.

    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
    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-Fri May 02 05:21:47 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA