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   44339   clinical trials with a EudraCT protocol, of which   7369   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:
    Pilot study to assess the safety and effect of SYL1001 in patients with ocular pain

    Summary
    EudraCT number
    		 2012-001177-93
    Trial protocol
    		 ES  
    Global end of trial date
    30 Apr 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Mar 2017
    First version publication date
    01 Mar 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SYL1001_II
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Sylentis SAU - Grupo PharmaMar
    Sponsor organisation address
    Parque Tecnológico de Madrid C/Santiago Grisolía nº 2, Tres Cantos, Madrid, Spain, 28760
    Public contact
    Head of Regulatory Affairs & QP, Sylentis S.A.U. , +34 918047667, info@sylentis.com
    Scientific contact
    Head of Regulatory Affairs & QP, Sylentis S.A.U. , +34 918047667, info@sylentis.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
    20 May 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Apr 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Apr 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    - Compare the analgesic effect of SYL1001 versus placebo - Compare the tolerability on the ocular surface (cornea and conjunctiva) in the treatment of ocular pain associated with dry eye syndrome.
    Protection of trial subjects
    The investigators and their collaborators undertook to accurately comply with the instructions of the Spanish Medical Deontological Code, the Declaration of Helsinki and the National Guidelines regarding clinical trials in humans (Royal Decree 223/2004, of 6 February). Furthermore, the study was conducted in accordance with the European Good Clinical Practice (CGP) guidelines.
    Background therapy
    		 -
    Evidence for comparator
    		 Evidence for comparator: In this trial, the same vehicle was used in the formulation of the investigational product (PBS) as placebo. The use of a placebo group in this clinical trial was justified due to the following facts: • Pain was a subjective symptom which was difficult to assess and using a placebo was essential to demonstrate the efficacy of the product. • There was currently no product of reference for treating this symptom and neither was there any established reference control. • All patients were strictly monitored and those patients whose condition deteriorated significantly during the study period could leave the study (voluntarily or according to the judgement of the investigator) and commence a treatment that the investigator considers to be most appropriate in each case (see the section regarding concomitant medication).
    Actual start date of recruitment
    01 Oct 2012
    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
    Spain: 61
    Worldwide total number of subjects
    61
    EEA total number of subjects
    61
    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)
    45
    From 65 to 84 years
    16
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 61 patients were included from 18/02/2013 to 08/04/2015

    Pre-assignment
    Screening details
    		 ≥ 18 years; IC sign;mild to moderate dry eye symptoms (OSDI 13-70 and VAS2-7);Eye tests in both eyes (Oxford>0,TBUT<10 sec, Schirmer´s test<10 mm/ 5m)

    Period 1
    Period 1 title
    Overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Subject
    Blinding implementation details
    The sponsor provided the vials with the study medication for each patient. Evaluation of the effect and ocular tolerance was performed in both eyes in a masked fashion meaning neither the patients nor the investigational team knew what medication the patients received. For each patient the sponsor provided single-dose vials with the study medication. The medication should be stored as specified by the Sponsor.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Patients assigned to placebo group received 40 μL of phosphate buffer saline solution for topical application without active ingredient once daily in each eye over a period of 10 days via the ophthalmic route.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Eye drops, solution
    Routes of administration
    Ophthalmic use
    Dosage and administration details
    Placebo: Supplied in vials of 0.1 mL with ophthalmic solution: NaCl 140 mM, Sodium phosphate 11 mM, pH 7.2 ± 0.5

    Arm title
    		 1.125% SYL1001
    Arm description
    		 Patients assigned to 1.125% SYL1001 arm received 40 μL of 1.125% ophthalmic solution (0.45 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).
    Arm type
    		 Experimental

    Investigational medicinal product name
    SYL1001
    Investigational medicinal product code
    SYL1001
    Other name
    Pharmaceutical forms
    Eye drops, solution
    Routes of administration
    Ophthalmic use
    Dosage and administration details
    This group received 40 μL of SYL1001 ophthalmic solution in both eyes. SYL1001 is a chemically synthesized 19-base small interfering oligonucleotide of RNA (siRNA) targeted to human Transient Receptor Potential Vanilloid 1 (TRPV1)

    Arm title
    		 2.25% SYL1001
    Arm description
    		 Patients assigned to any of the two SYL1001 arms received 40 μL of 2.25% ophthalmic solution (0.90 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).
    Arm type
    		 Experimental

    Investigational medicinal product name
    SYL1001
    Investigational medicinal product code
    SYL1001
    Other name
    Pharmaceutical forms
    Eye drops, solution
    Routes of administration
    Ophthalmic use
    Dosage and administration details
    This group received 40 μL of SYL1001 ophthalmic solution in both eyes. SYL1001 is a chemically synthesized 19-base small interfering oligonucleotide of RNA (siRNA) targeted to human Transient Receptor Potential Vanilloid 1 (TRPV1)

    Number of subjects in period 1 [1]
    		Placebo 1.125% SYL1001 2.25% SYL1001
    Started
    20
    20
    20
    Completed
    20
    20
    19
    Not completed
    0
    0
    1
         Consent withdrawn by subject
    -
    -
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: One patient was excluded because this patient was not treated

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Patients assigned to placebo group received 40 μL of phosphate buffer saline solution for topical application without active ingredient once daily in each eye over a period of 10 days via the ophthalmic route.

    Reporting group title
    1.125% SYL1001
    Reporting group description
    		 Patients assigned to 1.125% SYL1001 arm received 40 μL of 1.125% ophthalmic solution (0.45 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Reporting group title
    2.25% SYL1001
    Reporting group description
    		 Patients assigned to any of the two SYL1001 arms received 40 μL of 2.25% ophthalmic solution (0.90 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Reporting group values
    		 Placebo 1.125% SYL1001 2.25% SYL1001 Total
    Number of subjects
    		 20 20 20 60
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 17 15 13 45
        From 65-84 years
    		 3 5 7 15
    Age continuous
    Units: years
        median (full range (min-max))
    		 40.39 (23.56 to 75.38) 45.83 (27.36 to 76.35) 60.67 (27.89 to 78.23) -
    Gender categorical
    Units: Subjects
        Female
    		 15 17 18 50
        Male
    		 5 3 2 10
    Hyperemia - Right eye
    Units: Subjects
        Normal
    		 11 7 15 33
        Abnormal
    		 9 13 5 27
    Hyperemia - Left eye
    Units: Subjects
        Normal
    		 12 8 15 35
        Abnormal
    		 8 12 5 25
    Corneal fluorescein staining - Right eye
    Units: Subjects
        Oxford I
    		 14 12 13 39
        Oxford II
    		 5 7 6 18
        Oxford III
    		 1 1 1 3
    Corneal fluorescein staining - Left eye
    Units: Subjects
        Oxford I
    		 13 11 13 37
        Oxford II
    		 6 8 6 20
        Oxford III
    		 1 1 1 3
    Blepharitis - Right eye
    Units: Subjects
        Present
    		 11 11 13 35
        Absent
    		 9 9 7 25
    Blepharitis - Left eye
    Units: Subjects
        Present
    		 11 11 13 35
        Absent
    		 9 9 7 25
    Correct blinking and eyelid closure - Right eye
    Units: Subjects
        Correct
    		 20 19 20 59
        Incorrect
    		 0 1 0 1
    Correct blinking and eyelid closure - Left eye
    Units: Subjects
        Correct
    		 20 19 20 59
        Incorrect
    		 0 1 0 1
    Tear meniscus - Right eye
    Units: Subjects
        Normal
    		 9 9 5 23
        Thin
    		 11 11 15 37
    Tear meniscus - Left eye
    Units: Subjects
        Normal
    		 9 9 5 23
        Thin
    		 11 11 15 37
    SBP
    SBP=sistolic blood pressure
    Units: mmHg
        median (full range (min-max))
    		 111 (90 to 147) 116.5 (90 to 140) 112.5 (82 to 139) -
    DBP
    DBP=Diastolic blood pressure
    Units: mmHg
        median (full range (min-max))
    		 70 (50 to 91) 70 (60 to 87) 71.5 (57 to 86) -
    Heart rate
    Units: bpm
        median (full range (min-max))
    		 74 (51 to 96) 71 (48 to 82) 73 (55 to 89) -
    OSDI score
    OSDI: Ocular surface disease index
    Units: points
        median (full range (min-max))
    		 37.5 (22.9 to 70) 39.12 (13 to 62.5) 43.75 (20.45 to 63.64) -
    VAS score - Right eye
    VAS: Visual analogue scale
    Units: points
        median (full range (min-max))
    		 5 (2 to 7) 5 (2 to 7) 5 (2 to 7) -
    VAS score - Left eye
    VAS: Visual analogue scale
    Units: points
        median (full range (min-max))
    		 5 (2 to 7) 5.9 (2 to 7) 5.25 (2 to 7) -
    TBUT - Right eye
    TBUT = Tear break-up time
    Units: second
        median (full range (min-max))
    		 5 (2 to 9) 4 (1 to 9) 4 (1 to 8) -
    TBUT - Left eye
    TBUT= Tear break-up time
    Units: second
        median (full range (min-max))
    		 6 (1 to 9) 4 (1 to 9) 4 (1 to 8) -
    Schirmer’s test - Right eye
    Schirmer’s test with anesthesia
    Units: mm
        median (full range (min-max))
    		 5 (0 to 9) 4.5 (1 to 9) 4 (1 to 9) -
    Schirmer’s test - Left eye
    Schirmer’s test with anesthesia
    Units: mm
        median (full range (min-max))
    		 6 (1 to 9) 5 (0 to 9) 5.5 (1 to 9) -
    IOP - Right eye
    IOP= intraocular pressure
    Units: mmHg
        median (full range (min-max))
    		 14 (10 to 18) 16 (10 to 19) 14.5 (8 to 19) -
    IOP - Left eye
    IOP= intraocular pressure
    Units: mmHg
        median (full range (min-max))
    		 13 (10 to 17) 16 (11 to 21) 15 (6 to 19) -
    Visual acuity - Right eye
    Units: points
        median (full range (min-max))
    		 1 (0.4 to 1.2) 1 (0.5 to 1) 1 (0.7 to 1.25) -
    Visual acuity - Left eye
    Units: units
        median (full range (min-max))
    		 1 (0.7 to 1.2) 1 (0.5 to 1.2) 1 (0.9 to 1.25) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Patients assigned to placebo group received 40 μL of phosphate buffer saline solution for topical application without active ingredient once daily in each eye over a period of 10 days via the ophthalmic route.

    Reporting group title
    1.125% SYL1001
    Reporting group description
    		 Patients assigned to 1.125% SYL1001 arm received 40 μL of 1.125% ophthalmic solution (0.45 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Reporting group title
    2.25% SYL1001
    Reporting group description
    		 Patients assigned to any of the two SYL1001 arms received 40 μL of 2.25% ophthalmic solution (0.90 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All subjects who received any study drug (placebo included) and who participated in at least one post-day 0 assessment. This population coincided with the safety population and full analyses set (FAS)

    Subject analysis set title
    PP
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All subjects who adhered to the major criteria in the protocol, all subjects who completed at least one post-day 0 assessment of the primary endpoint, whose study drug administrations’ were greater than 75% (8 over 10) and who did not take any analgesic concomitant medication. Additionally patients with findings detected were excluded from PP

    Primary: Absolute change of OSDI score

    		 Close Top of page
    End point title
    		 Absolute change of OSDI score
    End point description
    OSDI=Ocular surface disease index
    End point type
    Primary
    End point timeframe
    Change from day 0 to day 10 post-administration
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: points
        arithmetic mean (confidence interval 95%)
    -12.51 (-19 to -6)
    -15.15 (-21.7 to -8.6)
    -7.6 (-14.2 to -1)
    Attachments
    		 OSDI score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2763
    Method
    		 ANCOVA
    Confidence interval

    Primary: Absolute change of OSDI score (PP)

    		 Close Top of page
    End point title
    		 Absolute change of OSDI score (PP)
    End point description
    End point type
    Primary
    End point timeframe
    at day 10 post-administration from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: points
        arithmetic mean (confidence interval 95%)
    -12.37 (-19.2 to -5.5)
    -15.2 (-21.8 to -8.6)
    -11.38 (-19.3 to -3.5)
    Attachments
    		 OSDI score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7298
    Method
    		 ANCOVA
    Confidence interval

    Primary: Absolute changes of VAS score at day 10 pre-administration

    		 Close Top of page
    End point title
    		 Absolute changes of VAS score at day 10 pre-administration
    End point description
    End point type
    Primary
    End point timeframe
    at day 10 pre-administration (24h after the 9th administration) from day 1
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: points
        arithmetic mean (confidence interval 95%)
    -0.98 (-1.5 to -0.4)
    -1.97 (-2.5 to -1.4)
    -1.1 (-1.7 to -0.5)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0255 [1]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [1] - Placebo vs 1.125% SYL1001: Dif 0.99 95%CI (0.2, 1.8) p=0.0127 Placebo vs 2.25% SYL1001: Dif 0.13 95%CI (-0.7, 0.9) p=0.7457 1.125% SYL1001 vs 2.25% SYL1001: Dif -0.87 95%CI (-1.7, 0.1) p=0.0300

    Primary: Absolute change of VAS score at day 10 post-administration

    		 Close Top of page
    End point title
    		 Absolute change of VAS score at day 10 post-administration
    End point description
    Due to protocol deviations, only 38 out of 60 patients could be included in this analysis. 22 patients did not have the measurement at day 10 post-treatment
    End point type
    Primary
    End point timeframe
    at day 10 post-administration (1h after the 10th administration) from day 1
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    12
    17
    11
    Units: points
        arithmetic mean (confidence interval 95%)
    -1.61 (-2.32 to -0.89)
    -2.24 (-2.83 to -1.64)
    -2.38 (-3.2 to -1.55)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.283
    Method
    		 ANCOVA
    Confidence interval

    Primary: Absolute change at day 10 post-treatment (imputation)

    		 Close Top of page
    End point title
    		 Absolute change at day 10 post-treatment (imputation)
    End point description
    Due to missing data at day 10 post-treatment, the change of the VAS scored was imputed using a imputation method which if VAS value at day 10 post-treatment was missing, it was set to the global mean VAS value in the corresponding treatment group (for all subjects) during the treatment period.
    End point type
    Primary
    End point timeframe
    at day 10 post-treatment from day 1
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: points
        arithmetic mean (confidence interval 95%)
    -1.55 (-2 to -1.1)
    -2.35 (-2.8 to -1.9)
    -2.65 (-3.1 to -2.2)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004 [2]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [2] - Placebo vs 1.125% SYL1001: Dif 0.80 95%CI (0.2, 1.4) p=0.0160 Placebo vs 2.25% SYL1001: Dif 1.01 95%CI (0.5, 1.7) p=0.0010 1.125% SYL1001 vs 2.25% SY1001: Dif 0.30 95%CI (-0.3, 0.9) p=0.3520

    Primary: Absolute changes of VAS score at day 10 pre-administration (PP)

    		 Close Top of page
    End point title
    		 Absolute changes of VAS score at day 10 pre-administration (PP)
    End point description
    End point type
    Primary
    End point timeframe
    at day 10 pre-administration (24h after the 9th administration) from day 1
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: points
        arithmetic mean (confidence interval 95%)
    -1.21 (-1.7 to -0.7)
    -1.98 (-2.5 to -1.5)
    -1.46 (-2.1 to -0.9)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.11
    Method
    		 ANCOVA
    Confidence interval

    Primary: Absolute change of VAS score at day 10 post-treatment (PP)

    		 Close Top of page
    End point title
    		 Absolute change of VAS score at day 10 post-treatment (PP)
    End point description
    End point type
    Primary
    End point timeframe
    at day 10 post-treatment (1h after the 10th administration) from day 1
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    11
    17
    8
    Units: points
        arithmetic mean (confidence interval 95%)
    -1.44 (-2.2 to -0.7)
    -2.27 (-2.9 to -1.7)
    -2.51 (-3.4 to -1.6)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.137
    Method
    		 ANCOVA
    Confidence interval

    Primary: Absolute change at day 10 post-treatment (imputation) (PP)

    		 Close Top of page
    End point title
    		 Absolute change at day 10 post-treatment (imputation) (PP)
    End point description
    Due to missing data at day 10 post-treatment, the change of the VAS score was imputed using a imputation method which if VAS value at day 10 post-treatment was missing, it was set to the global mean VAS value in the corresponding treatment group (for all subjects) during the treatment period.
    End point type
    Primary
    End point timeframe
    at day 10 post-treatment from day 1 using imputation method
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: points
        arithmetic mean (confidence interval 95%)
    -1.42 (-1.9 to -0.9)
    -2.4 (-2.9 to -1.9)
    -2.79 (-3.3 to -2.2)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [3]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [3] - Placebo vs 1.125% SYL1001: Dif 0.97 95%CI (0.3, 1.6) p=0.0060 Placebo vs 2.25% SYL1001: Dif 1.37 95%CI (0.6, 2.1) p=0.0010 1.125% SYL1001vs 2.25% SYL1001: Dif 0.40 95%CI (-0.3, 1.1) p=0.2710

    Primary: Absolute change of VAS score at each day from day 1

    		 Close Top of page
    End point title
    		 Absolute change of VAS score at each day from day 1
    End point description
    During the first three days of treatment, there were not significant differences between treatments. From day 4 until the end of treatment, the decrease of VAS was significantly higher in 1.125% SYL1001 compared to placebo.
    End point type
    Primary
    End point timeframe
    at each day from day 1
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: points
    arithmetic mean (confidence interval 95%)
        Day 2
    -0.58 (-1 to -0.1)
    -0.06 (-0.5 to 0.4)
    0.27 (-0.2 to 0.7)
        Day 3
    -0.31 (-0.8 to 0.2)
    -0.47 (-1 to 0.1)
    0.08 (-0.5 to 0.6)
        Day 4
    -0.61 (-1.1 to 0.1)
    -1.27 (-1.8 to 0.8)
    -0.04 (-0.5 to 0.5)
        Day 5
    -0.7 (-1.2 to -0.2)
    -1.46 (-1.9 to -1)
    -0.43 (-0.9 to 0)
        Day 6
    -0.88 (-1.4 to -0.4)
    -1.8 (-2.3 to -1.3)
    -0.72 (-1.2 to -0.2)
        Day 7
    -0.87 (-1.4 to -0.4)
    -2.02 (-2.5 to -1.5)
    -1.06 (-1.6 to -0.6)
        Day 8
    -0.68 (-1.3 to -0.1)
    -1.92 (-2.5 to -1.3)
    -0.91 (-1.5 to -0.3)
        Day 9
    -0.9 (-1.5 to -0.3)
    -1.92 (-2.5 to -1.3)
    -1.04 (-1.6 to -0.4)
        Day 10
    -0.98 (-1.5 to -0.4)
    -1.97 (-2.5 to -1.4)
    -1.1 (-1.7 to -0.5)
        Day 10 post
    -1.55 (-2 to -1.1)
    -2.35 (-2.8 to -1.9)
    -2.65 (-3.1 to -2.2)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    1.125% SYL1001 v Placebo v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4222 [4]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [4] - Pb-1.125% SYL1001: p (Dif CI95%) Day 2: 0.4222; Day 3: 0.6743; Day 4: 0.0633; Day 5: 0.0253 (0.76 (0.1,1.4)); Day 6: 0.0105 (0.91 (0.2,1.6)); Day 7: 0.0016 (1.15 (0.4,1.9)); Day 8: 0.0029 (1.24 (0.4,2.1)); Day 9: 0.0181 (1.02 (0.2,1.9)

    Primary: Change of hyperemia

    		 Close Top of page
    End point title
    		 Change of hyperemia
    End point description
    Improvement: patients with abnormal hyperemia at day 0 and normal hyperemia at day 10 Maintenance: patients with: Abnormal Hyperemia at day 0 and Abnormal Hyperemia at Day 10 or Normal Hyperemia at day 0 and Normal Hyperemia at Day 10 Worsening: patients with Normal Hyperemia at day 0 and Abnormal Hyperemia at Day 10 Two measurements (one for each eye) by patient
    End point type
    Primary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: Number
        Improvement
    7
    20
    4
        Maintenance
    29
    15
    34
        Worsening
    4
    5
    2
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001 [5]
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [5] - Pairwise comparisons (Bonferroni): 1vs2: 0.0134; 1vs3: 1.0000; 2vs3: 0.0002;

    Primary: Change of hyperemia (PP)

    		 Close Top of page
    End point title
    		 Change of hyperemia (PP)
    End point description
    Improvement: patients with abnormal hyperemia at day 0 and normal hyperemia at day 10 Maintenance: patients with: Abnormal Hyperemia at day 0 and Abnormal Hyperemia at Day 10 or Normal Hyperemia at day 0 and Normal Hyperemia at Day 10 Worsening: patients with Normal Hyperemia at day 0 and Abnormal Hyperemia at Day 10 Two measurements (one for each eye) by patient
    End point type
    Primary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: Number
        Improvement
    5
    20
    0
        Maintenance
    29
    15
    28
        Worsening
    2
    5
    0
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001 [6]
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [6] - Pairwise comparisons (Bonferroni): 1vs2: 0.0021; 1vs3: 0.1412; 2vs3: 0.0001;

    Primary: Change of corneal staining

    		 Close Top of page
    End point title
    		 Change of corneal staining
    End point description
    Two measurements (one for each eye) by patient Improvement of Corneal fluorescein staining: improve at least one degree the Oxford scale
    End point type
    Primary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: Number
        Improvement
    18
    27
    22
        Maintenance
    18
    12
    18
        Worsening
    4
    1
    0
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0743 [7]
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [7] - Improvement at least 2 degrees Oxford scale p-value=0.0012 (Pairwise comparisons (Bonferroni): 1vs2: 0.0542; 1vs3: 0.7057; 2vs3: 0.0024)

    Primary: Change of corneal staining (PP)

    		 Close Top of page
    End point title
    		 Change of corneal staining (PP)
    End point description
    Two measurements (one for each eye) by patient Improvement of Corneal fluorescein staining: improve at least one degree the Oxford scale
    End point type
    Primary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: Number
        Improvement
    16
    27
    14
        Maintenance
    16
    12
    14
        Worsening
    4
    1
    0
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0713 [8]
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [8] - Improvement at least 2 degrees Oxford scale p-value=0.0008 (Pairwise comparisons (Bonferroni): 1vs2: 0.0160; 1vs3: 1.0000; 2vs3: 0.0063)

    Secondary: Change of Blepharitis

    		 Close Top of page
    End point title
    		 Change of Blepharitis
    End point description
    Improvement: patient with present at day 0 and absent at day 10 Two measurements (one for each eye) by patient
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: Number
        Improvement
    6
    8
    4
        Maintenance
    33
    26
    32
        Worsening
    1
    6
    4
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6755
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Change of Blepharitis (PP)

    		 Close Top of page
    End point title
    		 Change of Blepharitis (PP)
    End point description
    Improvement: patient with present at day 0 and absent at day 10 Two measurements (one for each eye) by patient
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: Number
        Improvement
    6
    8
    0
        Maintenance
    29
    26
    26
        Worsening
    1
    6
    2
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1523
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Tear meniscus

    		 Close Top of page
    End point title
    		 Tear meniscus
    End point description
    Two measurements (one for each eye) by patient Improvement: patient with thin at day 0 and normal at day 10
    End point type
    Secondary
    End point timeframe
    at day 10 post-treatment from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: Number
        Improvement
    13
    8
    9
        Maintenance
    24
    26
    31
        Worsening
    3
    6
    0
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    1.125% SYL1001 v 2.25% SYL1001 v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5506
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Tear meniscus (PP)

    		 Close Top of page
    End point title
    		 Tear meniscus (PP)
    End point description
    Two measurements (one for each eye) by patient Improvement: patient with thin at day 0 and normal at day 10
    End point type
    Secondary
    End point timeframe
    at day 10 post-treatment from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: Number
        Improvement
    11
    8
    6
        Maintenance
    22
    26
    22
        Worsening
    3
    6
    0
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    1.125% SYL1001 v 2.25% SYL1001 v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5832
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Change of IOP

    		 Close Top of page
    End point title
    		 Change of IOP
    End point description
    IOP=Intraocular pressure
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: mmHg
        arithmetic mean (confidence interval 95%)
    -0.24 (-0.8 to 0.4)
    -0.29 (-0.9 to 0.3)
    -0.93 (-1.6 to -0.3)
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2573
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Change of IOP (PP)

    		 Close Top of page
    End point title
    		 Change of IOP (PP)
    End point description
    IOP=Intraocular pressure
    End point type
    Secondary
    End point timeframe
    at day 10 post-treatment from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: mmHg
        arithmetic mean (confidence interval 95%)
    -0.55 (-1.2 to 0.1)
    -1.12 (-1.8 to -0.5)
    -0.32 (-1.1 to 0.4)
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2525
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Change of BCVA

    		 Close Top of page
    End point title
    		 Change of BCVA
    End point description
    Visual acuity
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: points
        arithmetic mean (confidence interval 95%)
    0 (0 to 0)
    0 (0 to 0)
    0.02 (0 to 0.021)
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.641
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Change of BCVA (PP)

    		 Close Top of page
    End point title
    		 Change of BCVA (PP)
    End point description
    Visual acuity
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: points
        arithmetic mean (confidence interval 95%)
    -0.01 (-0.011 to 0)
    0 (0 to 0)
    0.01 (0 to 0.011)
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3721
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Change of TBUT

    		 Close Top of page
    End point title
    		 Change of TBUT
    End point description
    TBUT=tear break-up time
    End point type
    Secondary
    End point timeframe
    at day 10 post-treatment from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: seconds
        arithmetic mean (confidence interval 95%)
    0.75 (-0.4 to 1.9)
    1.85 (0.7 to 3)
    0.56 (-0.5 to 1.7)
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2192
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Change of TBUT (PP)

    		 Close Top of page
    End point title
    		 Change of TBUT (PP)
    End point description
    Tear break-up time
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: seconds
        arithmetic mean (confidence interval 95%)
    0.49 (-0.7 to 1.7)
    1.84 (0.7 to 2.9)
    0.47 (-0.8 to 1.8)
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1668
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Change of Schirmer´s test

    		 Close Top of page
    End point title
    		 Change of Schirmer´s test
    End point description
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    20
    20
    20
    Units: mm
        arithmetic mean (confidence interval 95%)
    4.42 (2.6 to 6.2)
    -0.11 (-1.9 to 1.7)
    2.56 (0.7 to 4.4)
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003 [9]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [9] - Placebo vs 1.125% SYL1001: Dif 4.53 95%CI(2.0, 7.1) p=0.0007 Placebo vs 2.25% SYL1001: Dif 1.86 95%CI(-0.7, 4.4) p=0.1552 1.125% SYL1001 vs 2.25% SYL1001: Dif -2.67 95%CI(-5.3, -0.1) p=0.0427

    Secondary: Change of Schirmer’s test (PP)

    		 Close Top of page
    End point title
    		 Change of Schirmer’s test (PP)
    End point description
    End point type
    Secondary
    End point timeframe
    at day 10 post-treatment from day 0
    End point values
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Number of subjects analysed
    18
    20
    14
    Units: mm
        arithmetic mean (confidence interval 95%)
    3.6 (2 to 5.2)
    -0.17 (-1.7 to 1.4)
    2.47 (0.6 to 4.3)
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 1.125% SYL1001 v 2.25% SYL1001
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0044 [10]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [10] - Placebo vs 1.125% SYL1001: Dif 3.77 95%CI(1.5, 6.0) p=0.0014 Placebo vs 2.25% SYL1001: Dif 1.12 95%CI(-1.4, 3.6) p=0.3717 1.125% SYL1001 vs 2.25% SYL1001: Dif -2.64 95%CI(-5.1, -0.2) p=0.0337

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Overall periods
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Patients assigned to placebo group received 40 μL of phosphate buffer saline solution for topical application without active ingredient once daily in each eye over a period of 10 days via the ophthalmic route.

    Reporting group title
    1.125% SYL1001
    Reporting group description
    		 Patients assigned to 1.125% SYL1001 arm received 40 μL of 1.125% ophthalmic solution (0.45 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Reporting group title
    2.25% SYL1001
    Reporting group description
    		 Patients assigned to any of the two SYL1001 arms received 40 μL of 2.25% ophthalmic solution (0.90 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Serious adverse events
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo 1.125% SYL1001 2.25% SYL1001
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 20 (10.00%)
    2 / 20 (10.00%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    3 / 20 (15.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    3
    0
    0
    Headache
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    0
    1
    General disorders and administration site conditions
    Malaise
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    1
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    1
    Eye pruritus
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    2
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    0
    0
    Abdominal discomfort
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Nov 2012
    New site: Fundación Jiménez Díaz (IP: Ignacio Jiménez-Alfaro Morote)
    03 May 2013
    New site: Hospital Ramón y Cajal (IP Francisco José Muñoz Negrete)
    05 Dec 2013
    The dose of the investigational medicinal product administered to patients in the study was changed. It went from being 900 micrograms/40 microliters to 450 micrograms/40 microliters. Protocol version v2.0 dated on December 5, 2013 and the version of the Patient Information Sheet and Informed Consent v3.0 dated December 5, 2013 were generated.
    03 Mar 2014
    New sites: - Clínica Universitaria de Navarra (IP: Dr. Javier Moreno Montañés) - Instituto Clínico Quirúrgico de Oftalmología (IP: Dr. Juan Antonio Durán de la Colina)

    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-Thu May 29 23:04:28 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA