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   43871   clinical trials with a EudraCT protocol, of which   7290   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:
    DOSE-FINDING STUDY TO ASSESS THE SAFETY AND EFFECT OF SYL1001 IN PATIENTS WITH OCULAR PAIN

    Summary
    EudraCT number
    		 2014-004857-15
    Trial protocol
    		 ES   EE  
    Global end of trial date
    10 Dec 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_III
    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
    10 Dec 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Dec 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    - Assessment of the analgesic effect of different doses of SYL1001 ophthalmic solution using the scoring of eye pain on the Visual Analogue Scale (VAS) and the scoring of ocular discomfort in the Ocular Surface Disease Index (OSDI) questionnaire. - Ocular tolerance at the site of administration (cornea and conjunctiva) after 10 days of treatment.
    Protection of trial subjects
    The investigators and their collaborators committed to conduct the study in accordance with the ICH guidelines and guidelines for Good Clinical Practice (GCP), with the Declaration of Helsinki (revised version, Fortaleza, October 2013) and the local laws and guidelines of the countries in which the study is being conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 In this trial, the same vehicle used in the formulation of the investigational product (PBS) was used 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 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 considered to be most appropriate in each case (see the section regarding concomitant medication).
    Actual start date of recruitment
    29 Jun 2015
    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: 43
    Country: Number of subjects enrolled
    Estonia: 25
    Worldwide total number of subjects
    68
    EEA total number of subjects
    68
    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)
    59
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 68 patints were included from 29/06/2015 to 19/11/2015.

    Pre-assignment
    Screening details
    		 ≥ 18 years of age, written consent Usual mild to moderate dry eye symptoms persistent and daily for more than 3 months (OSDI 13 -70,VAS 2-7) Eye tests in both eyes: Oxford scale>0, TBUT<10 sec, Schirmer´s test<10 mm/ 5m

    Pre-assignment period milestones
    Number of subjects started
    		 68
    Number of subjects completed
    		 66

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Concomitant medication with analgesic activity: 1
    Reason: Number of subjects
    		 Ocular test out of range: 1
    Period 1
    Period 1 title
    Overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    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
    Placeboo
    Other name
    Pharmaceutical forms
    Eye drops, solution
    Routes of administration
    Ophthalmic use
    Dosage and administration details
    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 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
    		 0.375% SYL1001
    Arm description
    		 Patients assigned to 0.357% SYL1001 arm received 40 μL of 0.375% ophthalmic solution (0.15 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
    Chemically synthesized 19-base small interfering oligonucleotide of RNA (siRNA) - 0.375% SYL1001: Supplied in vials of 0.1 ml with ophthalmic solution: SYL1001 3.75 mg/mL, pH: 7.2 ± 0.5 The patient went daily to the clinical site for the administration of medication to be administered by staff of the investigational team. The dose was administered with a pipette by placing the volume into the conjunctival sac, then closing the eye for about 10-20 seconds.

    Arm title
    		 0.75% SYL1001
    Arm description
    		 Patients assigned to 0.75% SYL1001 arm received 40 μL of 0.75% ophthalmic solution (0.30 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
    Chemically synthesized 19-base small interfering oligonucleotide of RNA (siRNA) - 0.75% SYL1001: Supplied in vials of 0.1 ml with ophthalmic solution: SYL1001 7.5 mg/mL, pH: 7.2 ± 0.5 The patient went daily to the clinical site for the administration of medication to be administered by staff of the investigational team. The dose was administered with a pipette by placing the volume into the conjunctival sac, then closing the eye for about 10-20 seconds.

    Number of subjects in period 1 [1]
    		Placebo 0.375% SYL1001 0.75% SYL1001
    Started
    24
    21
    21
    Completed
    24
    21
    20
    Not completed
    0
    0
    1
         Adverse event, non-fatal
    -
    -
    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: Two patients were not randomized and these patients were excluded from study

    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
    0.375% SYL1001
    Reporting group description
    		 Patients assigned to 0.357% SYL1001 arm received 40 μL of 0.375% ophthalmic solution (0.15 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Reporting group title
    0.75% SYL1001
    Reporting group description
    		 Patients assigned to 0.75% SYL1001 arm received 40 μL of 0.75% ophthalmic solution (0.30 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Reporting group values
    		 Placebo 0.375% SYL1001 0.75% SYL1001 Total
    Number of subjects
    		 24 21 21 66
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 21 18 19 58
        From 65-84 years
    		 3 3 2 8
    Age continuous
    Units: years
        median (full range (min-max))
    		 48 (26 to 76) 47 (19 to 72) 46 (38 to 52) -
    Gender categorical
    Units: Subjects
        Female
    		 22 18 17 57
        Male
    		 2 3 4 9
    Race
    Units: Subjects
        Caucasian
    		 23 21 20 64
        Hispanic
    		 1 0 1 2
    Relevant medical condition
    Units: Subjects
        Yes
    		 12 9 13 34
        No
    		 12 12 8 32
    Relevant ocular procedure
    Units: Subjects
        Yes
    		 2 2 0 4
        No
    		 22 19 21 62
    Relevant systemic procedure
    Units: Subjects
        Yes
    		 7 4 7 18
        No
    		 17 17 14 48
    Urine analysis
    Units: Subjects
        Positive
    		 9 7 11 27
        Negative
    		 15 14 10 39
    Hyperemia - Rigth eye
    Units: Subjects
        Normal
    		 16 8 10 34
        Abnormal
    		 8 13 11 32
    Hyperemia - Left eye
    Units: Subjects
        Normal
    		 16 9 10 35
        Abnormal
    		 8 12 11 31
    Corneal fluorescein staining - Right eye
    Oxford scale
    Units: Subjects
        Oxford I
    		 17 15 16 48
        Oxford II
    		 6 5 5 16
        Oxford III
    		 1 1 0 2
    Corneal fluorescein staining - Left eye
    Oxford scale
    Units: Subjects
        Oxford I
    		 16 14 16 46
        Oxford II
    		 6 5 5 16
        Oxford III
    		 2 2 0 4
    Blepharitis - Right eye
    Units: Subjects
        Present
    		 14 8 10 32
        Absent
    		 10 13 11 34
    Blepharitis - Left eye
    Units: Subjects
        Present
    		 14 8 10 32
        Absent
    		 10 13 11 34
    Altered eyelashes - Right eye
    Units: Subjects
        Present
    		 1 4 0 5
        Absent
    		 23 17 21 61
    Altered eyelashes - Left eye
    Units: Subjects
        Present
    		 2 4 0 6
        Absent
    		 22 17 21 60
    Correct blinking and eyelid closure - Right eye
    Units: Subjects
        Correct
    		 22 21 21 64
        Incorrect
    		 2 0 0 2
    Correct blinking and eyelid closure - left eye
    Units: Subjects
        Correct
    		 22 21 21 64
        Incorrect
    		 2 0 0 2
    Tear meniscus - Right eye
    Units: Subjects
        Normal
    		 8 6 10 24
        Thin
    		 16 15 11 42
    Tear meniscus - Left eye
    Units: Subjects
        Normal
    		 8 7 6 21
        Thin
    		 16 14 15 45
    Weight
    Units: Kg
        median (full range (min-max))
    		 64.4 (42.5 to 108) 67 (48 to 90.9) 60.5 (45 to 95) -
    Height
    Units: meters
        median (full range (min-max))
    		 1.62 (1.48 to 1.82) 1.63 (1.56 to 1.87) 1.67 (1.45 to 1.85) -
    BMI
    Body mass index
    Units: Kg/m2
        median (full range (min-max))
    		 24.6 (19.1 to 38.9) 23.6 (19.5 to 34.2) 22.4 (19 to 30.1) -
    SBP
    sistolic blood pressure
    Units: mmHg
        median (full range (min-max))
    		 120.5 (80 to 150) 120 (100 to 158) 120 (90 to 130) -
    DBP
    Diastolic blood pressure
    Units: mmHg
        median (full range (min-max))
    		 74 (60 to 90) 75 (60 to 109) 73 (60 to 89) -
    HR
    Heart rate
    Units: ppm
        median (full range (min-max))
    		 70.5 (61 to 94) 66 (60 to 99) 68 (60 to 92) -
    Temperature
    Units: Centigrades
        median (full range (min-max))
    		 36.5 (35.5 to 36.8) 36.5 (36 to 36.9) 36.5 (35.5 to 36.8) -
    Leucocytes
    Units: 10^3/μL
        median (full range (min-max))
    		 5.84 (4 to 10.7) 6.2 (4.6 to 9.5) 6 (2.8 to 8.8) -
    Neutrophils
    Units: 10^3/μL
        median (full range (min-max))
    		 3.25 (1.62 to 6.38) 3.3 (2.19 to 5) 3.18 (1.6 to 4.53) -
    Neutrophils
    Units: Percentage
        median (full range (min-max))
    		 53.95 (35.4 to 67.1) 52.9 (33.3 to 63.4) 52.2 (33.4 to 62.1) -
    Lymphocytes
    Units: 10^3/μL
        median (full range (min-max))
    		 2.21 (1.3 to 3.3) 2.09 (1.3 to 3.97) 2.06 (0.8 to 3.19) -
    Lymphocytes
    Units: Percentage
        median (full range (min-max))
    		 36 (22 to 54.8) 34.1 (22.3 to 47.1) 33.7 (21 to 50) -
    Monocytes
    Units: 10^3/μL
        median (full range (min-max))
    		 0.46 (0.2 to 0.86) 0.52 (0.37 to 0.8) 0.5 (0.28 to 0.91) -
    Monocytes
    Units: Percentages
        median (full range (min-max))
    		 7.95 (3.9 to 11.1) 8.6 (6.07 to 12.7) 8.4 (5.3 to 12.1) -
    Eosinophils
    Units: 10^3/μL
        median (full range (min-max))
    		 0.14 (0.08 to 0.53) 0.2 (0 to 0.43) 0.2 (0 to 0.63) -
    Eosinophils
    Units: Percentages
        median (full range (min-max))
    		 2.55 (1.14 to 6.1) 2.9 (0.7 to 6.5) 3.1 (0.6 to 9.9) -
    Basophils
    Units: 10^3/μL
        median (full range (min-max))
    		 0.04 (0 to 0.1) 0.04 (0 to 0.1) 0.04 (0 to 0.1) -
    Basophils
    Units: Percentages
        median (full range (min-max))
    		 0.7 (0.2 to 1.3) 0.6 (0.2 to 1.2) 0.7 (0.3 to 1.7) -
    RBC
    Red blood cells
    Units: 10^6/μL
        median (full range (min-max))
    		 4.58 (4.1 to 5.48) 4.74 (4.15 to 5.44) 4.63 (4.04 to 5.96) -
    Haemoglobin
    Units: g/dl
        median (full range (min-max))
    		 13.6 (12.4 to 16.6) 14.2 (13.1 to 15.5) 13.6 (11.7 to 15.3) -
    Haematocrite
    Units: percent
        median (full range (min-max))
    		 41.45 (36.4 to 47.2) 42.3 (38.5 to 46.1) 41.3 (37.8 to 45.5) -
    Platelets
    Units: 10^3/μL
        median (full range (min-max))
    		 253.5 (166 to 405) 240 (169 to 371) 251 (152 to 333) -
    MCV
    Units: fL
        median (full range (min-max))
    		 90.35 (83.4 to 98.5) 89.6 (83.3 to 99.5) 89.2 (74.5 to 94.7) -
    MCH
    Units: pg
        median (full range (min-max))
    		 30.05 (26.5 to 32.9) 29.6 (27.3 to 32.6) 29.4 (23.2 to 31.7) -
    MCHC
    Units: g/dl
        median (full range (min-max))
    		 32.9 (31.8 to 35.2) 33 (23.2 to 34.9) 32.9 (30.5 to 34.4) -
    Creatinine
    Units: mg/dl
        median (full range (min-max))
    		 0.7 (0.5 to 0.91) 0.72 (0.59 to 1.02) 0.84 (0.5 to 1.19) -
    Glucose
    Units: mg/dl
        median (full range (min-max))
    		 90 (63.33 to 110) 91 (68.33 to 106) 86 (75 to 98) -
    GOT
    Units: U/l
        median (full range (min-max))
    		 17 (10 to 41) 21 (11 to 33) 17 (13 to 23) -
    GPT
    Units: U/l
        median (full range (min-max))
    		 14 (7 to 59) 17 (7 to 37) 15 (9 to 28) -
    GGT
    Units: U/l
        median (full range (min-max))
    		 14.5 (8 to 53) 15 (11 to 80) 18 (7 to 47) -
    Alkaline phosphatase
    Units: U/l
        median (full range (min-max))
    		 58.5 (34 to 114) 53 (34 to 144) 46 (31 to 105) -
    Serum bilirubin
    Units: mg/dl
        median (full range (min-max))
    		 0.51 (0.2 to 1.05) 0.64 (0.35 to 1.23) 0.47 (0.13 to 1.35) -
    OSDI Score
    Ocular Surface Disease Index
    Units: points
        median (full range (min-max))
    		 46.75 (14.6 to 68.8) 43.8 (14.6 to 68.8) 41.7 (16.7 to 68.8) -
    Ocular vision-related subscore
    Units: points
        median (full range (min-max))
    		 33.33 (8.33 to 66.67) 25 (4.17 to 75) 29.17 (16.67 to 70.83) -
    Ocular discomfort-related subscore
    Units: points
        median (full range (min-max))
    		 56.25 (20.83 to 91.67) 54.17 (16.67 to 87.5) 54.17 (16.67 to 87.5) -
    VAS scale - Right eye
    Visual Analogue Scale day 1 Right eye
    Units: points
        median (full range (min-max))
    		 4.95 (1.5 to 7) 5 (2 to 7) 2 (2 to 7) -
    VAS scale - Left eye
    Visual Analogue Scale day 1 Left eye
    Units: points
        median (full range (min-max))
    		 4.95 (1.1 to 7) 5 (2.1 to 7) 5 (2 to 7) -
    TBUT - Right eye
    Tear break-up time
    Units: second
        median (full range (min-max))
    		 6 (2 to 8) 5 (3 to 8) 4 (1 to 8) -
    TBUT - Left eye
    Tear break-up time
    Units: second
        median (full range (min-max))
    		 5 (2 to 9) 5 (2 to 8) 5 (1 to 8) -
    Schirmer’s test - Right eye
    Units: mm
        median (full range (min-max))
    		 4 (1 to 9) 6 (1 to 9) 8 (1 to 9) -
    Schirmer’s test - Left eye
    Units: mm
        median (full range (min-max))
    		 6 (0 to 9) 7 (2 to 9) 6 (1 to 9) -
    IOP - Right eye
    Intraocular pressure
    Units: mmHg
        median (full range (min-max))
    		 15 (10 to 20) 15 (10 to 22) 14 (10 to 19) -
    IOP - Left eye
    Intraocular pressure
    Units: mmHg
        median (full range (min-max))
    		 15 (10 to 20) 15 (10 to 20) 15 (10 to 20) -
    Visual acuity - Right eye
    Units: points
        median (full range (min-max))
    		 1 (0.7 to 1) 1 (1 to 1) 1 (0.8 to 1) -
    Visual acuity - Left eye
    Units: points
        median (full range (min-max))
    		 1 (0.3 to 1) 1 (0.9 to 1) 1 (0.8 to 1) -

    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
    0.375% SYL1001
    Reporting group description
    		 Patients assigned to 0.357% SYL1001 arm received 40 μL of 0.375% ophthalmic solution (0.15 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Reporting group title
    0.75% SYL1001
    Reporting group description
    		 Patients assigned to 0.75% SYL1001 arm received 40 μL of 0.75% ophthalmic solution (0.30 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
    End point type
    Primary
    End point timeframe
    Change from day 0 to day 10 post-administration
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24
    21
    21
    Units: points
        arithmetic mean (confidence interval 95%)
    -17.59 (-24 to -11.2)
    -16.19 (-24 to -8.4)
    -16.45 (-23.8 to -9.1)
    Attachments
    		 OSDI score
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9839
    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23 [1]
    21
    19 [2]
    Units: points
        arithmetic mean (confidence interval 95%)
    -17.47 (-24.1 to -10.8)
    -16.19 (-24 to -8.4)
    -17.95 (-25.8 to -10.1)
    Attachments
    		 OSDI score
    Notes
    [1] - PP population
    [2] - PP population
    Statistical analysis title
    		 Differences between groups
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.989
    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24
    21
    21
    Units: points
        arithmetic mean (confidence interval 95%)
    -1.65 (-2.09 to -1.22)
    -1.58 (-2.04 to -1.12)
    -1.55 (-2.01 to -1.09)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Difference between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9401
    Method
    		 ANCOVA
    Confidence interval

    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
    End point type
    Primary
    End point timeframe
    at day 10 post-administration (1h after the 10th administration) from day 1
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24
    21
    21
    Units: points
        arithmetic mean (confidence interval 95%)
    -1.88 (-2.37 to -1.39)
    -2.12 (-2.64 to -1.6)
    -1.87 (-2.39 to -1.35)
    Attachments
    		 VAS
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7468
    Method
    		 ANCOVA
    Confidence interval

    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23
    21
    19
    Units: points
        arithmetic mean (confidence interval 95%)
    -1.74 (-2.18 to -1.3)
    -1.61 (-2.07 to -1.15)
    -1.6 (-2.09 to -1.12)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8947
    Method
    		 ANCOVA
    Confidence interval

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

    		 Close Top of page
    End point title
    		 Absolute change of VAS score at day 10 post-administration (PP)
    End point description
    End point type
    Primary
    End point timeframe
    at day 10 post-administration (1h after the 10th administration) from day 1
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23
    21
    19
    Units: points
        arithmetic mean (confidence interval 95%)
    -2.02 (-2.51 to -1.53)
    -2.15 (-2.67 to -1.64)
    -2.06 (-2.6 to -1.52)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    0.375% SYL1001 v 0.75% SYL1001 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9288
    Method
    		 ANCOVA
    Confidence interval

    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
    End point type
    Primary
    End point timeframe
    at each day from day 1
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24
    21
    21
    Units: points
    arithmetic mean (confidence interval 95%)
        Day 2
    -0.3 (-0.55 to -0.04)
    -0.13 (-0.4 to 0.14)
    -0.33 (-0.6 to -0.06)
        Day 3
    -0.66 (-1.01 to -0.31)
    -0.42 (-0.79 to -0.05)
    -0.01 (-0.38 to 0.36)
        Day 4
    -0.6 (-0.94 to -0.25)
    -0.49 (-0.85 to -0.12)
    -0.75 (-1.12 to -0.38)
        Day 5
    -0.99 (-1.3 to -0.68)
    -0.76 (-1.09 to -0.43)
    -0.85 (-1.18 to -0.52)
        Day 6
    -1.22 (-1.61 to -0.84)
    -0.86 (-1.27 to -0.45)
    -1 (-1.41 to -0.59)
        Day 7
    -1.46 (-1.83 to -1.09)
    -1.24 (-1.63 to -0.84)
    -1.23 (-1.63 to -0.84)
        Day 8
    -1.65 (-2.05 to -1.25)
    -1.25 (-1.68 to -0.82)
    -1.26 (-1.69 to -0.84)
        Day 9
    -1.6 (-2.03 to -1.17)
    -1.45 (-1.91 to -0.99)
    -1.6 (-2.06 to -1.14)
        Day 10
    -1.65 (-2.09 to -1.22)
    -1.58 (-2.04 to -1.12)
    -1.55 (-2.01 to -1.09)
        Day 10 post
    -1.88 (-2.37 to -1.39)
    -2.12 (-2.64 to -1.6)
    -1.87 (-2.39 to -1.35)
    Attachments
    		 VAS score
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5441 [3]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [3] - Day 2: 0.5441; Day 3: 0.0419 (Placebo-0.75% SYL1001: dif=-0.65 p=0.0124); Day 4: 0.5980; Day 5: 0.5932; Day 6: 0.4378; Day 7: 0.6284; Day 8: 0.2953; Day 9: 0.8643

    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24
    21
    21
    Units: percent of subjects
        Improvement
    2
    3
    9
        Maintenance
    44
    37
    28
        Worsening
    2
    2
    5
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0294 [4]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [4] - Pairwise comparisons (Bonferroni): 1vs2: 1.0000; 1vs3: 0.0344; 2vs3: 0.1888;

    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    21 [5]
    21 [6]
    19 [7]
    Units: percent of subjects
        Improvement
    2
    3
    9
        Maintenance
    42
    37
    24
        Worsening
    2
    2
    5
    Notes
    [5] - Two measurements (one for each eye) by patient
    [6] - Two measurements (one for each eye) by patient
    [7] - Two measurements (one for each eye) by patient
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.014 [8]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [8] - Pairwise comparisons (Bonferroni): 1vs2: 1.0000; 1vs3: 0.0204; 2vs3: 0.0965;

    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24 [9]
    21 [10]
    21 [11]
    Units: number of subjects
        Improvement
    25
    19
    19
        Maintenance
    23
    20
    23
        Worsening
    0
    3
    0
    Notes
    [9] - Two measurements (one for each eye) by patient
    [10] - Two measurements (one for each eye) by patient
    [11] - Two measurements (one for each eye) by patient
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1355
    Method
    		 Chi-squared
    Confidence interval

    Primary: Change of corneal staining (PP)

    		 Close Top of page
    End point title
    		 Change of corneal staining (PP)
    End point description
    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    21 [12]
    21 [13]
    19 [14]
    Units: number of subjects
        Improvement
    23
    19
    17
        Maintenance
    23
    20
    21
        Worsening
    0
    3
    0
    Notes
    [12] - Two measurements (one for each eye) by patient
    [13] - Two measurements (one for each eye) by patient
    [14] - Two measurements (one for each eye) by patient
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1715
    Method
    		 Chi-squared
    Confidence interval

    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
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24 [15]
    21 [16]
    21 [17]
    Units: number of subjects
        Improvement
    8
    6
    8
        Maintenance
    36
    34
    32
        Worsening
    4
    2
    2
    Notes
    [15] - Two measurements (one for each eye) by patient
    [16] - Two measurements (one for each eye) by patient
    [17] - Two measurements (one for each eye) by patient
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    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
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23 [18]
    21 [19]
    19 [20]
    Units: number of subjects
        Improvement
    8
    6
    8
        Maintenance
    34
    34
    28
        Worsening
    4
    2
    2
    Notes
    [18] - Two measurements (one for each eye) by patient
    [19] - Two measurements (one for each eye) by patient
    [20] - Two measurements (one for each eye) by patient
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9729
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Altered eyelashes

    		 Close Top of page
    End point title
    		 Altered eyelashes
    End point description
    Improvement: patient with present at day 0 and absent at day 10
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24 [21]
    21 [22]
    21 [23]
    Units: number of subjects
        Improvement
    3
    6
    0
        Maintenance
    45
    34
    40
        Worsening
    0
    2
    2
    Notes
    [21] - Two measurements (one for each eye) by patient
    [22] - Two measurements (one for each eye) by patient
    [23] - Two measurements (one for each eye) by patient
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2845
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Altered eyelashes (PP)

    		 Close Top of page
    End point title
    		 Altered eyelashes (PP)
    End point description
    Improvement: patient with present at day 0 and absent at day 10
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23 [24]
    21 [25]
    19 [26]
    Units: number of subjects
        Improvement
    3
    6
    0
        Maintenance
    43
    34
    36
        Worsening
    0
    2
    2
    Notes
    [24] - Two measurements (one for each eye) by patient
    [25] - Two measurements (one for each eye) by patient
    [26] - Two measurements (one for each eye) by patient
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3466
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Tear meniscus

    		 Close Top of page
    End point title
    		 Tear meniscus
    End point description
    Improvement: patient with thin at day 0 and normal at day 10
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24 [27]
    21 [28]
    21 [29]
    Units: number of subjects
        Improvement
    8
    9
    7
        Maintenance
    38
    31
    29
        Worsening
    2
    2
    6
    Notes
    [27] - Two measurements (one for each eye) by patient
    [28] - Two measurements (one for each eye) by patient
    [29] - Two measurements (one for each eye) by patient
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7023
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Tear meniscus (PP)

    		 Close Top of page
    End point title
    		 Tear meniscus (PP)
    End point description
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23 [30]
    21 [31]
    19 [32]
    Units: number of subjects
        Improvement
    6
    9
    7
        Maintenance
    38
    31
    27
        Worsening
    2
    2
    4
    Notes
    [30] - Two measurements (one for each eye) by patient
    [31] - Two measurements (one for each eye) by patient
    [32] - Two measurements (one for each eye) by patient
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    0.375% SYL1001 v Placebo v 0.75% SYL1001
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7182
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Change of IOP

    		 Close Top of page
    End point title
    		 Change of IOP
    End point description
    Intraocular pressure
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24
    21
    21
    Units: mmHg
        arithmetic mean (confidence interval 95%)
    -1.03 (-1.55 to -0.5)
    -0.41 (-0.96 to 0.15)
    -0.52 (-1.07 to 0.04)
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.229
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Change of IOP (PP)

    		 Close Top of page
    End point title
    		 Change of IOP (PP)
    End point description
    Intraocular pressure
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23
    21
    19
    Units: mmHg
        arithmetic mean (confidence interval 95%)
    -1.08 (-1.63 to -0.54)
    -0.41 (-0.96 to 0.15)
    -0.53 (-1.12 to 0.06)
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1979
    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24
    21
    21
    Units: points
        arithmetic mean (confidence interval 95%)
    -0.02 (-0.04 to -0.01)
    -0.01 (-0.03 to 0.01)
    0 (-0.02 to 0.01)
    Statistical analysis title
    		 Change of BCVA
    Comparison groups
    0.375% SYL1001 v 0.75% SYL1001 v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3075
    Method
    		 Chi-squared
    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23
    21
    19
    Units: points
        arithmetic mean (confidence interval 95%)
    -0.02 (-0.04 to -0.01)
    -0.01 (-0.03 to 0.01)
    -0.01 (-0.03 to 0.02)
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3103
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Change of TBUT

    		 Close Top of page
    End point title
    		 Change of TBUT
    End point description
    End point type
    Secondary
    End point timeframe
    at day 10 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24
    21
    21
    Units: second
        arithmetic mean (confidence interval 95%)
    0.13 (-0.63 to 0.88)
    0.14 (-0.67 to 0.95)
    1.31 (0.5 to 2.12)
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.063 [33]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [33] - Placebo vs 0.75% SYL1001 dif: -1.18 CI95% (-2.29, -0.07) p=0.0367 0.375% SYL1001 vs 0.75% SYL1001 dif: -1.17 CI95% (-2.31, -0.03) p=0.0449

    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23
    21
    19
    Units: second
        arithmetic mean (confidence interval 95%)
    0.27 (-0.5 to 1.05)
    0.14 (-0.67 to 0.95)
    1.4 (0.55 to 2.26)
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.071 [34]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [34] - Placebo vs 0.75% SYL1001 dif: -1.13 CI95%(-2.28, 0.02) p=0.0548 0.375% SYL1001 vs 0.75% SYL1001 dif: -1.26 CI95% (-2.44, -0.09) p=0.0357

    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 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    24
    21
    21
    Units: mm
        arithmetic mean (confidence interval 95%)
    0.36 (-0.58 to 1.31)
    0.74 (-0.27 to 1.75)
    0.82 (-0.19 to 1.83)
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7831
    Method
    		 ANCOVA
    Confidence interval

    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 from day 0
    End point values
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Number of subjects analysed
    23
    21
    19
    Units: mm
        arithmetic mean (confidence interval 95%)
    -0.06 (-0.97 to 0.86)
    0.75 (-0.2 to 1.69)
    1.16 (0.16 to 2.16)
    Statistical analysis title
    		 Differences between treatments
    Comparison groups
    Placebo v 0.375% SYL1001 v 0.75% SYL1001
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1987
    Method
    		 ANCOVA
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Overall period
    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
    0.375% SYL1001
    Reporting group description
    		 Patients assigned to 0.357% SYL1001 arm received 40 μL of 0.375% ophthalmic solution (0.15 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Reporting group title
    0.75% SYL1001
    Reporting group description
    		 Patients assigned to 0.75% SYL1001 arm received 40 μL of 0.75% ophthalmic solution (0.30 mg/eye/day) once daily in each eye over a period of 10 days via the ophthalmic route (ocular topical).

    Serious adverse events
    		 Placebo 0.375% SYL1001 0.75% SYL1001
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 21 (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 0.375% SYL1001 0.75% SYL1001
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 21 (0.00%)
    2 / 21 (9.52%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    1
    0
    2
    Eye disorders
    Eye pain
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 21 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    3
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 17:36:14 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA