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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35896   clinical trials with a EudraCT protocol, of which   5892   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).
     
    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:
    An exploratory, randomized, double-blind, double-dummy, placebo- and active-controlled Phase II trial to evaluate the efficacy and safety of a topical application of GRT7019 in subjects with chronic pain due to knee osteoarthritis

    Summary
    EudraCT number
    2016-002611-18
    Trial protocol
    AT   DE   ES  
    Global end of trial date
    17 Jan 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    17 Oct 2018
    First version publication date
    17 Oct 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    KF7019-01
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    U1111-1184-3912
    Sponsors
    Sponsor organisation name
    Grünenthal GmbH
    Sponsor organisation address
    Zieglerstr. 6, Aachen, Germany, 52078
    Public contact
    Grünenthal Trial Information Desk, Grünenthal GmbH, 0049 2415693223, Clinical-Trials@grunenthal.com
    Scientific contact
    Dr. Irmgard Bösl, Grünenthal GmbH, 0049 2415690, Clinical-Trials@grunenthal.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
    13 Aug 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Jan 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Evaluation of the analgesic efficacy of a once daily application of GRT7019 for 4 weeks compared to placebo.
    Protection of trial subjects
    The trial was conducted according to ICH-GCP guidelines, the applicable local laws and regulations, and in accordance with the ethical principles that have their origins in the Declaration of Helsinki. Regulatory authorities were notified of the trial as required by national regulations, and where necessary relevant authorization was obtained.
    Background therapy
    Allowed concomitant treatments included: Acetylsalicylic acid (oral doses less than or equal to 325 mg per day for cardiac prophylaxis). Hypnotics including benzodiazepines and non-benzodiazepines if previously used regularly according to the respective Summary of Product Characteristics (SmPCs) for at least 4 weeks prior to the Enrollment Visit and planned to continue on the same dose regimen throughout the trial. Selective serotonin reuptake inhibitors for the treatment of stable depression if previously used at a controlled, stable dose for at least 3 months prior to Enrollment Visit. Triptans for the treatment of migraine. Transcutaneous electrical nerve stimulation, acupuncture, and other physiotherapy, packs and massages, and psychological support were allowed during the trial, provided that the subjects had been on that therapy for at least 4 weeks prior to the Enrollment Visit and continued to undergo that therapy for the duration of the trials at the same frequency and intensity as before. Packs were only allowed if they did not apply external heat to the subject. For unacceptable pain due to chronic osteoarthritis during the trial, paracetamol tablets (500 mg) were provided as rescue medication to all treatment groups. No rescue medication was allowed during the last 3 days before the Baseline Visit. The maximum total daily dose of paracetamol was 2000 mg during the Washout Phase and after allocation to trial treatment until the Follow-up Visit. During the Treatment Period, paracetamol was not be taken for more than 3 consecutive days at the maximum allowed total daily dose. In the subjects randomized to the diclofenac treatment arm, over-encapsulated pantoprazole 20-mg tablets were provided once daily to prevent gastrointestinal system related injuries/bleeding that could result from the treatment with oral diclofenac.
    Evidence for comparator
    Diclofenac, an approved drug indicated for use in chronic pain due to osteoarthritis (OA) and recommended in treatment guidelines for OA (McAlindon et al. 2014, American Academy of Orthopaedic Surgeons 2013, Jordan et al. 2003), was selected as active comparator/standard of care to demonstrate assay sensitivity. The use of NSAIDs is also in line with The National Institute for Health and Care Excellence (NICE) recommendations for the pharmacological treatment of OA (NICE 2014). A lidocaine patch (Versatis®) was selected as comparator to fulfill in part the requirements of the draft Guideline on clinical development of fixed combination medicinal products (EMA/CHMP/281825/2015) to test the efficacy and show the tolerability profile of the individual component.
    Actual start date of recruitment
    12 Jun 2017
    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
    Poland: 29
    Country: Number of subjects enrolled
    Austria: 14
    Country: Number of subjects enrolled
    Germany: 116
    Country: Number of subjects enrolled
    Spain: 26
    Worldwide total number of subjects
    185
    EEA total number of subjects
    185
    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)
    117
    From 65 to 84 years
    68
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    A total of 229 subjects signed an informed consent at 29 active sites. 185 of these subjects were allocated to study drug (investigational medicinal product = IMP) and received IMP (46 subjects in the placebo arm, 46 in the GRT7019 arm, 48 in the diclofenac arm, and 45 in the lidocaine topical patch arm).

    Pre-assignment
    Screening details
    -

    Pre-assignment period milestones
    Number of subjects started
    229 [1]
    Number of subjects completed
    185

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Adverse event, non-fatal: 1
    Reason: Number of subjects
    Consent withdrawn by subject: 10
    Reason: Number of subjects
    Failure to meet randomization criteria: 31
    Reason: Number of subjects
    Technical reason: 1
    Reason: Number of subjects
    Other: 1
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 229 subjects signed an informed consent. 185 subjects received at least one dose of investigational medicinal product.
    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Placebo patches (matching GRT7019 and lidocaine 5% medicated plasters) and placebo capsules (matching over-encapsulated diclofenac sodium tablets)
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Medicated plaster
    Routes of administration
    Oral use, Topical use
    Dosage and administration details
    All IMPs were administered in a double-dummy design to maintain the blinding. A placebo patch (matching GRT7019 and lidocaine 5% medicated plaster) was administered once daily for 4 weeks with a wearing time of up to 18 hours but not less than 11 hours. Placebo patches, approximately 14 x 10 cm, should have been administered in the morning at a time suitable to accommodate the subjects’ needs and had to be fixed at the bent knee with an elastic mesh bandage. Placebo capsules matching the over-encapsulated diclofenac tablets were administered twice daily, i.e., in the morning (before a meal) and in the evening, for 4 weeks. A placebo capsule matching pantoprazole tablets was taken once daily in the morning for 4 weeks.

    Arm title
    GRT7019
    Arm description
    A fixed-dose combination patch containing 5% lidocaine (700 mg) and 1.3% diclofenac epolamine (182 mg)
    Arm type
    Experimental

    Investigational medicinal product name
    GRT7019
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Medicated plaster
    Routes of administration
    Topical use
    Dosage and administration details
    All IMPs were administered in a double-dummy design to maintain the blinding. GRT7019 patches were administered once daily for 4 weeks with a wearing time of up to 18 hours but not less than 11 hours. The patches, approximately 14 x 10 cm, should have been administered in the morning at a time suitable to accommodate the subjects’ needs and had to be fixed at the bent knee with an elastic mesh bandage. Placebo capsules matching the over-encapsulated diclofenac tablets were administered twice daily, i.e., in the morning (before a meal) and in the evening, for 4 weeks. A placebo capsule matching pantoprazole tablets was taken once daily in the morning for 4 weeks.

    Arm title
    Diclofenac
    Arm description
    Over-encapsulated diclofenac sodium sustained-release (62.5 mg)/immediate-release (12.5 mg) tablets.
    Arm type
    Active comparator

    Investigational medicinal product name
    Diclofenac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    All IMPs were administered in a double-dummy design to maintain the blinding. A diclofenac capsule (containing 62.5 mg sustained-release and 12.5 mg immediate-release diclofenac sodium) was administered orally twice daily, i.e., in the morning (before a meal) and in the evening, for 4 weeks. Over-encapsulated pantoprazole 20-mg tablets were taken once daily to prevent gastrointestinal system related injuries/bleeding that could result from the treatment with oral diclofenac. A placebo patch (matching GRT7019 and lidocaine 5% medicated plaster) was administered once daily for 4 weeks with a wearing time of up to 18 hours but not less than 11 hours. Placebo patches should have been administered in the morning at a time suitable to accommodate the subjects’ needs and must be fixed at the bent knee with an elastic mesh bandage.

    Arm title
    Lidocaine 5% medicated plaster
    Arm description
    Versatis® (lidocaine 5% medicated plaster, containing 700 mg lidocaine)
    Arm type
    Active comparator

    Investigational medicinal product name
    Lidocaine 5% medicated plaster
    Investigational medicinal product code
    Other name
    Versatis
    Pharmaceutical forms
    Medicated plaster
    Routes of administration
    Topical use
    Dosage and administration details
    Lidocaine 5% medicated plasters were applied once daily for 4 weeks with a wearing time of up to 18 hours and a minimum wearing time of 11 hours. Patches should have been administered in the morning to accommodate the subject's needs and were required to be fixed at the bent knee with an elastic mesh bandage. Placebo capsules matching the over-encapsulated diclofenac tablets were administered twice daily, i.e., in the morning (before a meal) and in the evening, for 4 weeks. A placebo capsule matching pantoprazole tablets was taken once daily in the morning for 4 weeks.

    Number of subjects in period 1
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Started
    46
    46
    48
    45
    Completed
    41
    42
    39
    42
    Not completed
    5
    4
    9
    3
         Technical reason
    -
    -
    1
    -
         Protocol deviation
    1
    1
    -
    -
         Missing
    2
    -
    2
    2
         Lack of efficacy
    -
    -
    1
    -
         Adverse event, non-fatal
    2
    1
    2
    -
         Consent withdrawn by subject
    -
    2
    3
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo patches (matching GRT7019 and lidocaine 5% medicated plasters) and placebo capsules (matching over-encapsulated diclofenac sodium tablets)

    Reporting group title
    GRT7019
    Reporting group description
    A fixed-dose combination patch containing 5% lidocaine (700 mg) and 1.3% diclofenac epolamine (182 mg)

    Reporting group title
    Diclofenac
    Reporting group description
    Over-encapsulated diclofenac sodium sustained-release (62.5 mg)/immediate-release (12.5 mg) tablets.

    Reporting group title
    Lidocaine 5% medicated plaster
    Reporting group description
    Versatis® (lidocaine 5% medicated plaster, containing 700 mg lidocaine)

    Reporting group values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster Total
    Number of subjects
    46 46 48 45 185
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    31 26 29 31 117
        Adults (65-84 years)
    15 20 19 14 68
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    61.2 ± 8.0 63.4 ± 7.5 61.2 ± 8.6 60.7 ± 9.0 -
    Gender categorical
    Units: Subjects
        Female
    27 30 36 28 121
        Male
    19 16 12 17 64
    Race
    Units: Subjects
        White
    45 46 48 44 183
        American Indian or Alaska Native
    1 0 0 0 1
        Native Hawaiian or Other Pacific Islander
    0 0 0 1 1
    Height
    Units: meter
        arithmetic mean (standard deviation)
    1.707 ± 0.089 1.68 ± 0.095 1.672 ± 0.08 1.708 ± 0.091 -
    Weight
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    83.1 ± 13.9 83.1 ± 13.6 83.0 ± 12.3 83.1 ± 15.4 -
    Body Mass Index
    Units: kilogram(s)/square meter
        arithmetic mean (standard deviation)
    28.4 ± 3.6 29.3 ± 3.5 29.8 ± 4.2 28.4 ± 3.7 -
    WOMAC index score
    The WOMAC index score was calculated for the Full Analysis Set by summarizing the scores for the pain, stiffness and physical function subscales (as described by McConnel S, Kolopack P, Davis AM. The Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties. Arthritis Rheum 2001; 45(5):453-61.)
    Units: units on a scale
        arithmetic mean (standard deviation)
    NA ± NA NA ± NA NA ± NA NA ± NA -
    Baseline pain intensity
    Baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the evening pain intensity of Day -3 up to the morning value of Day 1). Pain intensities were assessed by the subject in an eDiary twice daily (in the morning and the evening) using an 11-point NRS (where 0 = no pain and 10 = pain as bad as you can imagine).
    Units: units on a scale
        arithmetic mean (standard deviation)
    NA ± NA NA ± NA NA ± NA NA ± NA -
    History of osteoarthritis
    Answer to the question: "When were you diagnosed with OA of the knee?"
    Units: years
        arithmetic mean (standard deviation)
    9.0 ± 8.4 9.7 ± 8.3 11.5 ± 10.8 11.0 ± 9.8 -
    Subject analysis sets

    Subject analysis set title
    Placebo FAS
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

    Subject analysis set title
    GRT7019 FAS
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

    Subject analysis set title
    Diclofenac FAS
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

    Subject analysis set title
    Lidocaine 5% medicated plaster FAS
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

    Subject analysis sets values
    Placebo FAS GRT7019 FAS Diclofenac FAS Lidocaine 5% medicated plaster FAS
    Number of subjects
    46
    45
    47
    45
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    31
    26
    29
    31
        Adults (65-84 years)
    15
    19
    18
    14
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    61.2 ± 8.0
    63.3 ± 7.5
    61.0 ± 8.7
    60.7 ± 9.0
    Gender categorical
    Units: Subjects
        Female
    27
    29
    35
    28
        Male
    19
    16
    12
    17
    Race
    Units: Subjects
        White
    46
    45
    47
    44
        American Indian or Alaska Native
    1
    0
    0
    0
        Native Hawaiian or Other Pacific Islander
    0
    0
    0
    1
    Height
    Units: meter
        arithmetic mean (standard deviation)
    170.7 ± 8.9
    168.0 ± 9.6
    167.3 ± 8.1
    170.8 ± 9.1
    Weight
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    83.1 ± 13.9
    83.4 ± 13.5
    83.2 ± 12.4
    83.1 ± 15.4
    Body Mass Index
    Units: kilogram(s)/square meter
        arithmetic mean (standard deviation)
    28.4 ± 3.6
    29.5 ± 3.5
    29.8 ± 4.3
    28.4 ± 3.7
    WOMAC index score
    The WOMAC index score was calculated for the Full Analysis Set by summarizing the scores for the pain, stiffness and physical function subscales (as described by McConnel S, Kolopack P, Davis AM. The Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties. Arthritis Rheum 2001; 45(5):453-61.)
    Units: units on a scale
        arithmetic mean (standard deviation)
    50.9 ± 11.3
    43.5 ± 12.5
    48.7 ± 11.0
    49.7 ± 11.0
    Baseline pain intensity
    Baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the evening pain intensity of Day -3 up to the morning value of Day 1). Pain intensities were assessed by the subject in an eDiary twice daily (in the morning and the evening) using an 11-point NRS (where 0 = no pain and 10 = pain as bad as you can imagine).
    Units: units on a scale
        arithmetic mean (standard deviation)
    5.76 ± 0.93
    5.59 ± 0.90
    5.55 ± 0.78
    5.69 ± 0.98
    History of osteoarthritis
    Answer to the question: "When were you diagnosed with OA of the knee?"
    Units: years
        arithmetic mean (standard deviation)
    NA ± NA
    NA ± NA
    NA ± NA
    NA ± NA

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo patches (matching GRT7019 and lidocaine 5% medicated plasters) and placebo capsules (matching over-encapsulated diclofenac sodium tablets)

    Reporting group title
    GRT7019
    Reporting group description
    A fixed-dose combination patch containing 5% lidocaine (700 mg) and 1.3% diclofenac epolamine (182 mg)

    Reporting group title
    Diclofenac
    Reporting group description
    Over-encapsulated diclofenac sodium sustained-release (62.5 mg)/immediate-release (12.5 mg) tablets.

    Reporting group title
    Lidocaine 5% medicated plaster
    Reporting group description
    Versatis® (lidocaine 5% medicated plaster, containing 700 mg lidocaine)

    Subject analysis set title
    Placebo FAS
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

    Subject analysis set title
    GRT7019 FAS
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

    Subject analysis set title
    Diclofenac FAS
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

    Subject analysis set title
    Lidocaine 5% medicated plaster FAS
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

    Primary: Change from baseline to week 4 of the double-blind treatment period in the weekly average pain intensity

    Close Top of page
    End point title
    Change from baseline to week 4 of the double-blind treatment period in the weekly average pain intensity
    End point description
    The primary endpoint was the change from baseline to Week 4 of the double-blind Treatment Period in the weekly average pain intensity. The baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the evening pain intensity of Day -3 up to the morning value of Day 1). Pain intensity was recorded twice daily (morning and evening) using an 11-point Numeric Rating Scale (NRS) with a half-day recall period (where 0 = no pain and 10 = Pain as bad as you can imagine). The weekly average pain was defined as the average of the non-missing weekly average morning and weekly average evening pain intensity assessments per trial week.
    End point type
    Primary
    End point timeframe
    Baseline to Week 4 of the double-blind Treatment Period. Subjects used their eDiary to record their current pain intensity between 06:00 h and 09:00 h in the morning and once between 19:00 h and 22:00 h in the evening.
    End point values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Number of subjects analysed
    40 [1]
    41 [2]
    39 [3]
    41 [4]
    Units: units on a scale
        least squares mean (standard error)
    -2.03 ± 0.27
    -1.83 ± 0.27
    -2.16 ± 0.26
    -1.44 ± 0.27
    Notes
    [1] - Full Analysis Set
    [2] - Full Analysis Set
    [3] - Full Analysis Set
    [4] - Full Analysis Set
    Statistical analysis title
    GRT7019 versus placebo
    Statistical analysis description
    MMRM with fixed effects of pooled sites, treatment, time (in weeks), treatment-by-time interaction, positive expectancy score (of SETS questionnaire), and baseline intensity score. An unstructured covariance matrix is used to model the covariance structure, while denominator degrees of freedom are estimated using the Kenward-Roger approximation. The analysis was performed based on all post-baseline weekly pain intensities using only the observed cases without imputation of missing values.
    Comparison groups
    GRT7019 v Placebo
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    Method
    MMRM
    Parameter type
    MMRM
    Point estimate
    0.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    0.92
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36

    Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current morning pain intensity

    Close Top of page
    End point title
    Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current morning pain intensity
    End point description
    The average morning pain intensity is the mean of the morning pain intensities assessed once daily in the morning using an 11-point NRS (where 0 = no pain and 10 = pain as bad as you can imagine) and asking the subject to “Please indicate how much osteoarthritis knee pain you have right now by selecting one number". A negative change indicates that there was a decrease in pain. If there were 4 or more missing morning pain intensity assessments in a week, the value for the weekly average morning pain intensity was set to missing.
    End point type
    Secondary
    End point timeframe
    Baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the morning pain intensity of Day -3 up to the morning value of Day 1), the change was up to 31 days after the start of treatment.
    End point values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Number of subjects analysed
    46 [5]
    45 [6]
    47 [7]
    45 [8]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Change from baseline to Week 1
    -1.4 ± 1.2
    -1.1 ± 1.2
    -1.5 ± 1.4
    -1.2 ± 1.4
        Change from baseline to Week 2
    -1.9 ± 1.5
    -1.7 ± 1.7
    -2.0 ± 1.8
    -1.6 ± 1.6
        Change from baseline to Week 3
    -2.1 ± 1.6
    -1.9 ± 1.8
    -2.3 ± 1.8
    -1.6 ± 1.5
        Change from baseline to Week 4
    -2.2 ± 1.6
    -2.0 ± 1.7
    -2.2 ± 2.0
    -1.7 ± 1.5
    Notes
    [5] - Full Analysis Set (N = 45 at Week 1) (N = 44 at Week 2) (N = 41 at Week 3) (N = 40 at Week 4)
    [6] - Full Analysis Set (N = 45 at Week 1) (N = 45 at Week 2) (N = 42 at Week 3) (N = 41 at Week 4)
    [7] - Full Analysis Set (N = 47 at Week 1) (N = 46 at Week 2) (N = 41 at Week 3) (N = 39 at Week 4)
    [8] - Full Analysis Set (N = 45 at Week 1) (N = 45 at Week 2) (N = 44 at Week 3) (N = 42 at Week 4)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current evening pain intensity

    Close Top of page
    End point title
    Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current evening pain intensity
    End point description
    The average evening pain intensity is the mean of the evening pain intensities assessed once daily in the evening using an 11-point NRS (where 0 = no pain and 10 = pain as bad as you can imagine) and asking the subject to “Please indicate how much osteoarthritis knee pain you have right now by selecting one number.” A negative change indicates that there was a decrease in pain. If there were 4 or more missing evening pain intensity assessments in a week, the value for the weekly average evening pain intensity was set to missing.
    End point type
    Secondary
    End point timeframe
    Baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the evening pain intensity of Day -3 up to the evening value of Day 1), the change was up to 31 days after the start of treatment.
    End point values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Number of subjects analysed
    46 [9]
    45 [10]
    47 [11]
    45 [12]
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Change from baseline to Week 1
    -1.5 ± 1.3
    -0.8 ± 1.4
    -1.6 ± 1.3
    -0.9 ± 1.5
        Change from baseline to Week 2
    -2.0 ± 1.4
    -1.5 ± 1.6
    -2.2 ± 1.7
    -1.5 ± 1.7
        Change from baseline to Week 3
    -2.2 ± 1.6
    -1.8 ± 1.7
    -2.4 ± 1.8
    -1.5 ± 1.7
        Change from baseline to Week 4
    -2.2 ± 1.7
    -1.9 ± 1.6
    -2.5 ± 2.0
    -1.6 ± 1.9
    Notes
    [9] - Full Analysis Set (N = 45 at Week 1) (N = 46 at Week 2) (N = 43 at Week 3) (N = 43 at Week 4)
    [10] - Full Analysis Set (N = 45 at Week 1) (N = 45 at Week 2) (N = 42 at Week 3) (N = 41 at Week 4)
    [11] - Full Analysis Set (N = 47 at Week 1) (N = 46 at Week 2) (N = 43 at Week 3) (N = 40 at Week 4)
    [12] - Full Analysis Set (N = 44 at Week 1) (N = 45 at Week 2) (N = 44 at Week 3) (N = 42 at Week 4)
    No statistical analyses for this end point

    Secondary: Assessment of responder rate

    Close Top of page
    End point title
    Assessment of responder rate
    End point description
    A subject is listed as responder in the responder status if both sub-criteria ("At least 30% pain reduction at Week 4 on an 11-point NRS" and "Rescue medication intake at most 500 mg") are fulfilled.
    End point type
    Secondary
    End point timeframe
    From first dose of investigational medicinal product (IMP) to Week 4 (End of the double-blind Treatment Period).
    End point values
    Placebo FAS GRT7019 FAS Diclofenac FAS Lidocaine 5% medicated plaster FAS
    Number of subjects analysed
    46 [13]
    45 [14]
    47 [15]
    45 [16]
    Units: subjects
        Responder
    19
    19
    23
    16
        Non responder
    27
    26
    24
    29
        At least 30% pain reduction at Week 4
    20
    21
    24
    16
        Rescue medication intake at most 500mg
    39
    36
    39
    41
    Notes
    [13] - Full Analysis Set
    [14] - Full Analysis Set
    [15] - Full Analysis Set
    [16] - Full Analysis Set
    No statistical analyses for this end point

    Secondary: Change from baseline in pain intensity after physical exercise

    Close Top of page
    End point title
    Change from baseline in pain intensity after physical exercise
    End point description
    Subjects were asked at the investigational site to walk a stair for 1 minute (Andersson et al. 2010). Pain was recorded on an 11-point Numeric Rating Scale (where 0 = no pain to 10 = pain as bad as you can imagine) directly afterwards by asking the question "Please indicate how much osteoarthritis knee pain you have right now by selecting one number". A negative change in pain intensity score indicates that there has been a decrease in pain from baseline.
    End point type
    Secondary
    End point timeframe
    At Final Visit 29 days after starting treatment.
    End point values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Number of subjects analysed
    44 [17]
    43 [18]
    42 [19]
    45 [20]
    Units: units of a scale
        arithmetic mean (standard deviation)
    -2.0 ± 2.1
    -2.2 ± 1.9
    -2.2 ± 2.2
    -1.5 ± 2.3
    Notes
    [17] - Full Analysis Set
    [18] - Full Analysis Set
    [19] - Full Analysis Set
    [20] - Full Analysis Set
    No statistical analyses for this end point

    Secondary: Average daily rescue medication intake during Week 4 of the double-blind Treatment Period

    Close Top of page
    End point title
    Average daily rescue medication intake during Week 4 of the double-blind Treatment Period
    End point description
    The average daily rescue medication intake was calculated from the information captured in the eDiary reported in Week 4. In case of missing diary information, a day was imputed with 500 mg paracetamol intake.
    End point type
    Secondary
    End point timeframe
    Final Visit 29 days after start of treatment.
    End point values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Number of subjects analysed
    43 [21]
    42 [22]
    42 [23]
    44 [24]
    Units: milligram(s)/24 hours
        arithmetic mean (standard deviation)
    150.5 ± 368.9
    177.4 ± 359.0
    101.2 ± 301.0
    119.3 ± 333.6
    Notes
    [21] - Full Analysis Set
    [22] - Full Analysis Set
    [23] - Full Analysis Set
    [24] - Full Analysis Set
    No statistical analyses for this end point

    Secondary: Changes from baseline in Western Ontario McMaster Score

    Close Top of page
    End point title
    Changes from baseline in Western Ontario McMaster Score
    End point description
    The WOMAC is a valid, reliable, and responsive measure of outcome in knee OA (Roos et al. 1999). The WOMAC version used was the WOMAC™ LK3.1, 5-point Likert format. The WOMAC was chosen as a complementary assessment of efficacy. The scores of the 3 subscales pain, stiffness, physical function and the WOMAC index score were calculated. Each of the 5 response categories was assigned a numerical value (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = extreme). Each WOMAC subscale score was calculated by a simple summation of the assigned values scored on the items. The WOMAC index score was calculated by summating the scores for the 3 subscales (McConnel et al. 2001). A negative value indicates that there has been an improvement since baseline.
    End point type
    Secondary
    End point timeframe
    Final Visit 29 days after the start of treatment.
    End point values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Number of subjects analysed
    44 [25]
    43 [26]
    43 [27]
    45 [28]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Change in WOMAC Index Score
    -17.8 ± 15.7
    -13.9 ± 13.1
    -20.3 ± 15.1
    -15.9 ± 15.7
        Change in WOMAC Subscale Pain
    -4.1 ± 3.7
    -3.7 ± 3.2
    -4.6 ± 3.5
    -3.6 ± 3.3
        Change in WOMAC Subscale Stiffness
    -1.5 ± 1.7
    -1.0 ± 1.6
    -1.7 ± 1.3
    -1.2 ± 1.6
        Change in WOMAXC Subscale Physical Function
    -12.2 ± 11.5
    -9.2 ± 9.8
    -13.9 ± 11.5
    -11.0 ± 11.9
    Notes
    [25] - Full Analysis Set
    [26] - Full Analysis Set
    [27] - Full Analysis Set
    [28] - Full Analysis Set
    No statistical analyses for this end point

    Secondary: Patient Global Impression of Change (PGIC)

    Close Top of page
    End point title
    Patient Global Impression of Change (PGIC)
    End point description
    Patient Global Impression of Change used a 7-point scale at Final Visit. The subject was asked to respond by indicating which category fitted best to the question: "Since the start of the study, my overall status is": “Very much improved”, “Much improved”, “Minimally improved", ”No change” , “Minimally worse”, “Much worse”, or “Very much worse”.
    End point type
    Secondary
    End point timeframe
    Final Visit 29 Days after starting treatment.
    End point values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Number of subjects analysed
    46 [29]
    45 [30]
    47 [31]
    45 [32]
    Units: subjects
        Very much improved
    2
    3
    9
    5
        Much improved
    13
    12
    17
    12
        Minimally improved
    18
    22
    10
    14
        No change
    9
    6
    5
    11
        Minimally worse
    1
    0
    1
    3
        Much worse
    1
    0
    0
    0
        Very much worse
    0
    0
    0
    0
        Missing
    2
    2
    5
    0
    Notes
    [29] - Full Analysis Set
    [30] - Full Analysis Set
    [31] - Full Analysis Set
    [32] - Full Analysis Set
    No statistical analyses for this end point

    Secondary: Clinician’s Global Impression of Change (CGIC)

    Close Top of page
    End point title
    Clinician’s Global Impression of Change (CGIC)
    End point description
    The Clinician's Global Impression of Change used a 7-point scale at Final Visit. The clinician was asked to respond by indicating which category fitted best to the question: "Compared with the patient’s condition at Baseline, how has it changed?": “Very much improved”, “Much improved”, “Minimally improved", ”No change” , “Minimally worse”, “Much worse”, or “Very much worse”.
    End point type
    Secondary
    End point timeframe
    Final Visit 29 days after start of treatment.
    End point values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Number of subjects analysed
    46 [33]
    45 [34]
    47 [35]
    45 [36]
    Units: subjects
        Very much improved
    2
    3
    9
    1
        Much improved
    16
    15
    19
    16
        Minimally improved
    14
    16
    9
    13
        No change
    9
    9
    6
    13
        Minimally worse
    2
    0
    0
    2
        Much worse
    1
    0
    0
    0
        Very much worse
    0
    0
    0
    0
        Missing
    2
    2
    4
    0
    Notes
    [33] - Full Analysis Set
    [34] - Full Analysis Set
    [35] - Full Analysis Set
    [36] - Full Analysis Set
    No statistical analyses for this end point

    Secondary: Incidence of treatment emergent adverse events

    Close Top of page
    End point title
    Incidence of treatment emergent adverse events
    End point description
    The number of subjects were categorized by the number of Treatment Emergent Adverse Events (none, one, two, three, four, five or more than 5 TEAEs).
    End point type
    Secondary
    End point timeframe
    Final Follow-up Visit 31 days after start of treatment.
    End point values
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Number of subjects analysed
    46 [37]
    46 [38]
    48 [39]
    45 [40]
    Units: subjects
        No TEAEs
    30
    34
    27
    29
        One TEAE
    10
    8
    15
    13
        Two TEAEs
    6
    3
    6
    3
        Three TEAEs
    0
    1
    0
    0
        Four TEAEs
    0
    0
    0
    0
        Five TEAEs
    0
    0
    0
    0
        More than 5 TEAEs
    0
    0
    0
    0
    Notes
    [37] - Safety Set
    [38] - Safety Set
    [39] - Safety Set
    [40] - Safety Set
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Treatment Emergent Adverse Events (TEAEs) reported include all Adverse Events occuring after first topical application or oral intake of investigational medicinal product (IMP) up to and including Visit 7 (Follow-up visit, i.e. scheduled for Day 31).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo patches (matching GRT7019 and lidocaine 5% medicated plasters) and placebo capsules (matching over-encapsulated diclofenac sodium tablets)

    Reporting group title
    GRT7019
    Reporting group description
    A fixed-dose combination patch containing 5% lidocaine (700 mg) and 1.3% diclofenac epolamine (182 mg)

    Reporting group title
    Diclofenac
    Reporting group description
    Over-encapsulated diclofenac sodium sustained-release (62.5 mg)/immediate-release (12.5 mg) tablets

    Reporting group title
    Lidocaine 5% medicated plaster
    Reporting group description
    Versatis® (lidocaine 5% medicated plaster, containing 700 mg lidocaine)

    Serious adverse events
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 46 (2.17%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (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
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea exertional
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (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
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Placebo GRT7019 Diclofenac Lidocaine 5% medicated plaster
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 46 (32.61%)
    11 / 46 (23.91%)
    21 / 48 (43.75%)
    16 / 45 (35.56%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Immune system disorders
    Food allergy
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    General disorders and administration site conditions
    Application site erythema
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Application site haematoma
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Application site haemorrhage
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Application site pruritus
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    Application site reaction
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Application site warmth
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Malaise
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Peripheral swelling
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Intentional overdose
         subjects affected / exposed
    3 / 46 (6.52%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Procedural pain
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tendon rupture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Investigations
    Blood creatine increased
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Glomerular filtration rate decreased
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    2 / 48 (4.17%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    2
    1
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Catarrh
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Headache
         subjects affected / exposed
    1 / 46 (2.17%)
    1 / 46 (2.17%)
    1 / 48 (2.08%)
    1 / 45 (2.22%)
         occurrences all number
    1
    1
    1
    1
    Paraesthesia
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    2 / 48 (4.17%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Abdominal pain upper
         subjects affected / exposed
    2 / 46 (4.35%)
    2 / 46 (4.35%)
    1 / 48 (2.08%)
    1 / 45 (2.22%)
         occurrences all number
    2
    2
    1
    1
    Diarrhoea
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    2 / 48 (4.17%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    2
    1
    Dyspepsia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Faeces soft
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal pain
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haematochezia
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Toothache
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Dandruff
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Erythema
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Petechiae
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 46 (2.17%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Joint swelling
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    5 / 48 (10.42%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    5
    1
    Bronchitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Cystitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Influenza
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    1 / 48 (2.08%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 46 (0.00%)
    0 / 48 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    3

    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA