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   43874   clinical trials with a EudraCT protocol, of which   7294   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:
    Randomized, controlled, double-blind, multi-center trial to evaluate the efficacy and safety of an Etofenamate 5% cutaneous patch vs. Placebo in the treatment of acute uncomplicated unilateral ankle sprain

    Summary
    EudraCT number
    		 2016-000252-99
    Trial protocol
    		 DE  
    Global end of trial date
    27 Apr 2017

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    DRO-200/III/15/1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Drossapharm AG
    Sponsor organisation address
    Birsweg 1, Arlesheim, Switzerland, 4144
    Public contact
    Dr. Roger Imboden, Drossapharm AG, 0041 617051000, roger.imboden@drossapharm.ch
    Scientific contact
    Dr. Roger Imboden, Drossapharm AG, 0041 617051000, roger.imboden@drossapharm.ch
    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
    09 Oct 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Apr 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Apr 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of an Etofenamate 5% cutaneous patch applied two times a day compared with a placebo patch in patients with acute ankle sprains, in particular with regard to pain relief.
    Protection of trial subjects
    Patients were monitored throughout participation in the study for adverse events.
    Background therapy
    		 As necessary: Use of a crutch, exercise(Achilles’ tendon stretching), muscle strengthening exercises only after range of motion has been regained. Standard care by rest, ice, compression (non-occlusive bandage), or elevation (RICE) at the discretion of the Investigator. Rescue medication (paracetamol) except for the 6 hours prior to Visit 4 (48 h), Visit 5 (72 h) and Visit 6 (96 h).
    Evidence for comparator
    		 Placebo patch was indistinguishable from the investigational drug etofenamate 5% cutaneous patch.
    Actual start date of recruitment
    03 Sep 2016
    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
    Germany: 156
    Worldwide total number of subjects
    156
    EEA total number of subjects
    156
    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)
    156
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients were enrolled in the clinical trial by five investigators in Germany. To qualify for participation, patients had to experience an acute Grade I or II sprain of the ankle within the previous 12 hours. Patients were to be randomized as soon as possible after the injury.

    Pre-assignment
    Screening details
    		 To minimize unnecessary risks to patients they were to be screened at baseline to ensure absence of the various clinical disorders described in the exclusion criteria. This process included a baseline physical examination, vital signs, medical and drug history.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Patients were treated with etofenamate 5% cutaneous patch or with a matching placebo patch.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Etofenamate 5% cutaneous patch
    Arm description
    		 Patients were treated with a cutaneous patch containing 5% etofenamate.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etofenamate 5% cutaneous patch
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Cutaneous patch
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The patch was applied twice daily for 7 days.

    Arm title
    		 Placebo
    Arm description
    		 Patients were treated with a matching placebo patch.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Cutaneous patch
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The patch was applied twice daily for 7 days.

    Number of subjects in period 1
    		Etofenamate 5% cutaneous patch Placebo
    Started
    78
    78
    Completed
    78
    78

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 156 156
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 156 156
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age continuous
    According to the study protocol patients ages 18-60 years could be enrolled.
    Units: years
        arithmetic mean (standard deviation)
    		 35.3 ( 11.8 ) -
    Gender categorical
    Units: Subjects
        Female
    		 64 64
        Male
    		 92 92
    Subject analysis sets

    Subject analysis set title
    Full Analysis Set (FAS) etofenamate 5% cutaneous patch
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The FAS includes all randomized patients who received at least one dose of IMP. The FAS population is the primary population for the analysis of efficacy. The intention-to-treat (ITT) population is identical to the full analysis set (FAS).

    Subject analysis set title
    Full Analysis Set (FAS) placebo patch
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The FAS includes all randomized patients who received at least one dose of study treatment. The FAS population is the primary population for the analysis of efficacy. The intention-to-treat (ITT) population is identical to the full analysis set (FAS).

    Subject analysis sets values
    		 Full Analysis Set (FAS) etofenamate 5% cutaneous patch Full Analysis Set (FAS) placebo patch
    Number of subjects
    78
    78
    Age categorical
    Units: Subjects
        In utero
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    0
    0
        Adults (18-64 years)
    78
    78
        From 65-84 years
    0
    0
        85 years and over
    0
    0
    Age continuous
    According to the study protocol patients ages 18-60 years could be enrolled.
    Units: years
        arithmetic mean (standard deviation)
    33.8 ( 11.6 )
    36.9 ( 11.9 )
    Gender categorical
    Units: Subjects
        Female
    28
    36
        Male
    50
    42

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Etofenamate 5% cutaneous patch
    Reporting group description
    		 Patients were treated with a cutaneous patch containing 5% etofenamate.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were treated with a matching placebo patch.

    Subject analysis set title
    Full Analysis Set (FAS) etofenamate 5% cutaneous patch
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The FAS includes all randomized patients who received at least one dose of IMP. The FAS population is the primary population for the analysis of efficacy. The intention-to-treat (ITT) population is identical to the full analysis set (FAS).

    Subject analysis set title
    Full Analysis Set (FAS) placebo patch
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The FAS includes all randomized patients who received at least one dose of study treatment. The FAS population is the primary population for the analysis of efficacy. The intention-to-treat (ITT) population is identical to the full analysis set (FAS).

    Primary: Ankle pain-on-movement (POM)

    		 Close Top of page
    End point title
    		 Ankle pain-on-movement (POM)
    End point description
    Ankle-pain on movement was assessed in mm using a 100 mm Visual Analogue Scale (VAS) (0 mm = ‘no pain’, and 100 mm = ‘extreme pain’).
    End point type
    Primary
    End point timeframe
    Assessed at Visit 5 (72 hours after initiation of treatment).
    End point values
    		 Etofenamate 5% cutaneous patch Placebo
    Number of subjects analysed
    78
    78
    Units: mm
        arithmetic mean (standard deviation)
    36.3 ( 21.8 )
    57.4 ( 16.1 )
    Statistical analysis title
    		 ANCOVA
    Statistical analysis description
    For quantitative efficacy outcomes assessed at the clinical trial sites (pain-on-movement, pain-at rest, ankle swelling) and derived outcomes (area-under-the-curve) null hypotheses were tested with an analysis of covariance (ANCOVA) model. For comparisons using the specified ANCOVA models above, the least square mean for each treatment and the corresponding difference between least square means (EFM 5% patch - Placebo) with the p-value and 95% confidence interval were presented from the model.
    Comparison groups
    Etofenamate 5% cutaneous patch v Placebo
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean
    Point estimate
    22.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.2
         upper limit
    		 26
    Variability estimate
    Standard deviation

    Secondary: Ankle-pain on movement at visit 4

    		 Close Top of page
    End point title
    		 Ankle-pain on movement at visit 4
    End point description
    Ankle-pain on movement was assessed in mm using a 100 mm Visual Analogue Scale (VAS) (0 mm = ‘no pain’, and 100 mm = ‘extreme pain’).
    End point type
    Secondary
    End point timeframe
    Assessed at Visit 4 (48 hours after initiation of treatment).
    End point values
    		 Etofenamate 5% cutaneous patch Placebo
    Number of subjects analysed
    78
    78
    Units: mm
        arithmetic mean (standard deviation)
    46.5 ( 22.3 )
    62.8 ( 14.8 )
    Statistical analysis title
    		 ANCOVA
    Statistical analysis description
    For quantitative efficacy outcomes assessed at the clinical trial sites (pain-on-movement, pain-at rest, ankle swelling) and derived outcomes (area-under-the-curve) null hypotheses were tested with an analysis of covariance (ANCOVA) model. For comparisons using the specified ANCOVA models above, the least square mean for each treatment and the corresponding difference between least square means (EFM 5% patch - Placebo) with the p-value and 95% confidence interval were presented from the model.
    Comparison groups
    Etofenamate 5% cutaneous patch v Placebo
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean
    Point estimate
    17.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.5
         upper limit
    		 21.3
    Variability estimate
    Standard deviation

    Secondary: Ankle-pain on movement at Visit 6

    		 Close Top of page
    End point title
    		 Ankle-pain on movement at Visit 6
    End point description
    Ankle-pain on movement was assessed in mm using a 100 mm Visual Analogue Scale (VAS) (0 mm = ‘no pain’, and 100 mm = ‘extreme pain’).
    End point type
    Secondary
    End point timeframe
    Assessed at Visit 6 (96 hours after initiation treatment).
    End point values
    		 Etofenamate 5% cutaneous patch Placebo
    Number of subjects analysed
    78
    78
    Units: mm
        arithmetic mean (standard deviation)
    27.9 ( 21.6 )
    50.1 ( 17.4 )
    Statistical analysis title
    		 ANCOVA
    Statistical analysis description
    For quantitative efficacy outcomes assessed at the clinical trial sites (pain-on-movement, pain-at rest, ankle swelling) and derived outcomes (area-under-the-curve) null hypotheses were tested with an analysis of covariance (ANCOVA) model. For comparisons using the specified ANCOVA models above, the least square mean for each treatment and the corresponding difference between least square means (EFM 5% patch - Placebo) with the p-value and 95% confidence interval were presented from the model.
    Comparison groups
    Etofenamate 5% cutaneous patch v Placebo
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean
    Point estimate
    23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.9
         upper limit
    		 27.1
    Variability estimate
    Standard deviation

    Secondary: Ankle-pain on movemement at Visit 7

    		 Close Top of page
    End point title
    		 Ankle-pain on movemement at Visit 7
    End point description
    Ankle-pain on movement was assessed in mm using a 100 mm Visual Analogue Scale (VAS) (0 mm = ‘no pain’, and 100 mm = ‘extreme pain’).
    End point type
    Secondary
    End point timeframe
    Assessed at Visit 7 (Day 8 (±1) after initiation of treatment.
    End point values
    		 Etofenamate 5% cutaneous patch Placebo
    Number of subjects analysed
    78
    78
    Units: mm
        arithmetic mean (standard deviation)
    12.8 ( 13.5 )
    31.2 ( 17.9 )
    Statistical analysis title
    		 ANCOVA
    Statistical analysis description
    For quantitative efficacy outcomes assessed at the clinical trial sites (pain-on-movement, pain-at rest, ankle swelling) and derived outcomes (area-under-the-curve) null hypotheses were tested with an analysis of covariance (ANCOVA) model. For comparisons using the specified ANCOVA models above, the least square mean for each treatment and the corresponding difference between least square means (EFM 5% patch - Placebo) with the p-value and 95% confidence interval were presented from the model.
    Comparison groups
    Etofenamate 5% cutaneous patch v Placebo
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean
    Point estimate
    19.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.8
         upper limit
    		 23.4
    Variability estimate
    Standard deviation

    Secondary: Ankle-pain at rest at Visit 5

    		 Close Top of page
    End point title
    		 Ankle-pain at rest at Visit 5
    End point description
    Ankle-pain at rest was assessed in mm using a 100 mm Visual Analogue Scale (VAS) (0 mm = ‘no pain’, and 100 mm = ‘extreme pain’).
    End point type
    Secondary
    End point timeframe
    Assessed at Visit 5 (72 h after initiation of treatment)
    End point values
    		 Etofenamate 5% cutaneous patch Placebo
    Number of subjects analysed
    78
    78
    Units: mm
        arithmetic mean (standard deviation)
    12.5 ( 12.6 )
    17.9 ( 15.0 )
    Statistical analysis title
    		 ANCOVA
    Statistical analysis description
    For quantitative efficacy outcomes assessed at the clinical trial sites (pain-on-movement, pain-at rest, ankle swelling) and derived outcomes (area-under-the-curve) null hypotheses were tested with an analysis of covariance (ANCOVA) model. For comparisons using the specified ANCOVA models above, the least square mean for each treatment and the corresponding difference between least square means (EFM 5% patch - Placebo) with the p-value and 95% confidence interval were presented from the model.
    Comparison groups
    Placebo v Etofenamate 5% cutaneous patch
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean
    Point estimate
    6.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.8
         upper limit
    		 9.5
    Variability estimate
    Standard deviation

    Secondary: AUC of pain on movement at Visit 5

    		 Close Top of page
    End point title
    		 AUC of pain on movement at Visit 5
    End point description
    The area-under-the-curve (AUC) over time between baseline and the first 72 hours was calculated by means of the trapezoidal rule for POM measured by VAS.
    End point type
    Secondary
    End point timeframe
    0 - 72 h after initiation of treatment
    End point values
    		 Etofenamate 5% cutaneous patch Placebo
    Number of subjects analysed
    78
    78
    Units: mm * h
        arithmetic mean (standard deviation)
    3851.2 ( 1266.5 )
    4655.5 ( 926.9 )
    Statistical analysis title
    		 ANCOVA
    Statistical analysis description
    For quantitative efficacy outcomes assessed at the clinical trial sites (pain-on-movement, pain-at rest, ankle swelling) and derived outcomes (area-under-the-curve) null hypotheses were tested with an analysis of covariance (ANCOVA) model. For comparisons using the specified ANCOVA models above, the least square mean for each treatment and the corresponding difference between least square means (EFM 5% patch - Placebo) with the p-value and 95% confidence interval were presented from the model.
    Comparison groups
    Etofenamate 5% cutaneous patch v Placebo
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean
    Point estimate
    879.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 677.3
         upper limit
    		 1081.7
    Variability estimate
    Standard deviation

    Secondary: Circumference (ankle swelling)

    		 Close Top of page
    End point title
    		 Circumference (ankle swelling)
    End point description
    The circumference measurements of ankle swelling as further secondary variable were carried out by “Figure-of-eight-method” comparing the injured ankle with the contralateral site.
    End point type
    Secondary
    End point timeframe
    Visit 5 (72 h after initiation of treatment)
    End point values
    		 Etofenamate 5% cutaneous patch Placebo
    Number of subjects analysed
    78
    78
    Units: cm
        arithmetic mean (standard deviation)
    1.0 ( 0.9 )
    1.3 ( 1.0 )
    Statistical analysis title
    		 ANCOVA
    Statistical analysis description
    For quantitative efficacy outcomes assessed at the clinical trial sites (pain-on-movement, pain-at rest, ankle swelling) and derived outcomes (area-under-the-curve) null hypotheses were tested with an analysis of covariance (ANCOVA) model. For comparisons using the specified ANCOVA models above, the least square mean for each treatment and the corresponding difference between least square means (EFM 5% patch - Placebo) with the p-value and 95% confidence interval were presented from the model.
    Comparison groups
    Etofenamate 5% cutaneous patch v Placebo
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 0.4

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were documented from visit 1 (randomization, initiation of treatment) until visit 7 (day 7+1 of treatment)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Etofenamate 5% cutaneous patch
    Reporting group description
    		 Patients were treated with a cutaneous patch containing 5% etofenamate.

    Reporting group title
    Placebo patch
    Reporting group description
    		 Patients were treated with a matching placebo cutaneous patch.

    Serious adverse events
    		 Etofenamate 5% cutaneous patch Placebo patch
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 78 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Etofenamate 5% cutaneous patch Placebo patch
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 78 (2.56%)
    3 / 78 (3.85%)
    Nervous system disorders
    headache
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 78 (1.28%)
         occurrences all number
    1
    1
    General disorders and administration site conditions
    Application site erythema
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 78 (1.28%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 78 (1.28%)
         occurrences all number
    0
    1
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 78 (0.00%)
         occurrences all number
    1
    0

    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
    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-Thu May 16 18:55:07 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA