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:
    Efficacy and Safety of sublingual immunotherapy with Allergoid LAIS® Grass tablets for patients with grass pollen-induced allergic rhinoconjunctivitis, a phase III study

    Summary
    EudraCT number
    		 2012-004916-79
    Trial protocol
    		 DE  
    Global end of trial date
    08 Sep 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Apr 2022
    First version publication date
    21 Apr 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SMART_10
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Lofarma Spa
    Sponsor organisation address
    Viale Cassala, 40, Milan, Italy, 20143
    Public contact
    Head of Scientific Department, Head of Scientific Department, +39 02581981,
    Scientific contact
    Head of Scientific Department, Head of Scientific Department, +39 02581981,
    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
    03 Sep 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Sep 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to assess the efficacy of sublingual immunotherapy with the allergoid LAIS®Grass tablets by the total combined score (TCS) taking in account the rhinoconjunctivitis total symptom score (RTSS) of the six rhinoconjunctivitis symptoms (sneezing, rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus and watery eyes and the total rescue medication score (TRMS) for the peak of the grass pollen season.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles which have their origins in the Declaration of Helsinki. Thus the Declaration of Helsinki, the GCP (Good Clinical Practice) guidelines (Committee of Proprietary Medicinal Products/ International Conference on Harmonization, CPMP/ICH/135/95) as well as the requirements of national drug and data protection laws and other applicable regulatory requirements have been strictly followed throughout the entire process. A copy of The Declaration of Helsinki and the ICH/GCP guidelines were included in each Investigator’s file (see Reference List). In conformity with the ICH guidelines, patients participating in the study were covered by the clinical trial insurance for test subjects. The insurance policy was issued by Allianz Global Corporate & Speciality AG, Königinstr. 28, 80802 Munich, policy number: DEL 004158130.
    Background therapy
    		 The intake of anti-symptomatic medication appropriate to an escalation scheme was documented daily in a patient diary and evaluated afterwards using a score. It was recommended to the patients to start the treatment of the seasonally allergic symptoms with oral antihistamines (step 1 - 1 X 10 mg). In the case of ongoing eye symptoms additional Levocabastine eye drops (step 2 - 2 x 1 drop per eye) were recommended. If the nasal symptoms were not alleviated, nasal corticosteroids (Beclomethasone) (step 3 - 2 x 0.05 mg/per nostril) could be applied.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Dec 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 9 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 157
    Worldwide total number of subjects
    157
    EEA total number of subjects
    157
    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)
    157
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Trial has been conducted in Germany. It was planned to recruit 200 patients in total, with 100 participants in each treatment group. A total number of 157 patients were recruited and screened for inclusion and exclusion criteria; 90 eligible patients were randomized and included into the statistical analyses.

    Pre-assignment
    Screening details
    		 90 patients were randomized at V1. 2 patients were excluded as per protocol violation. Both patients were in the placebo group and treated only for a short time. Therefore 88 patients performed V2. Patients (Pt) dropp-out: 1Pt following V2 - 1Pt at V3 - 2Pt at V4 - 3Pt at V5. Finally, 81 patients finished the study.

    Period 1
    Period 1 title
    Grass pollen (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Data analyst, Subject
    Blinding implementation details
    Sealed envelopes, one for each randomization code, contained the declaration of the corresponding treatment and were deposited at the study centre. The sealed envelopes were only to be opened upon any patient-related event which required unblinding even if knowledge of the kind of treatment might have influenced the management of this event.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Placebo and verum preparations were identical except of the active substances (carbamylated, monomeric allergoids of grass)
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    Independent of the assigned treatment group, the patients ingested one sublingual tablet per day. The participants were instructed to place the tablet under the tongue and to let it dissolve for two minutes before swallowing. The first application on day 0 was performed under supervision of the investigator and the patients remained under the observation of a trained allergologist for at least 30 minutes. Afterwards, trial medication was handed to the patients and was self-administered by the patient.

    Arm title
    		 LAIS® Grass Tablets
    Arm description
    		 The active ingredients of 1,000 UA-LAIS®Grass sublingual tablets were carbamylated, monomeric allergoids consisting of timothy grass (Phleum pratense), common meadow grass (Poa pratensis) and meadow soft grass (Holcus lanatus) in equal parts. Excipients were lactose, mycrocrystalline cellulosa, silica dioxide and magnesium stearate for each tablet
    Arm type
    		 Experimental

    Investigational medicinal product name
    LAIS® Grass Tablets
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    Independent of the assigned treatment group, the patients ingested one sublingual tablet per day. The participants were instructed to place the tablet under the tongue and to let it dissolve for two minutes before swallowing. The first application on day 0 was performed under supervision of the investigator and the patients remained under the observation of a trained allergologist for at least 30 minutes. Afterwards, trial medication was handed to the patients and was self-administered by the patient.

    Number of subjects in period 1 [1]
    		Placebo LAIS® Grass Tablets
    Started
    44
    46
    Completed
    37
    44
    Not completed
    7
    2
         Lack of Compliance
    1
    -
         Consent withdrawn by subject
    4
    1
         Adverse event, non-fatal
    -
    1
         Late screening failure
    2
    -
    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: For this study, 157 patients were screened. Since 67 patients were omitted as screening failures, 90 patients were randomized into the study. No patient was lost to follow up. A total of nine patients dropped out.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Grass pollen
    Reporting group description
    		 -

    Reporting group values
    		 Grass pollen Total
    Number of subjects
    		 90 90
    Age categorical
    Units: Subjects
        Adults (18-75)
    		 90 90
    Age continuous
    Units: years
        median (full range (min-max))
    		 38.4 (18 to 69) -
    Gender categorical
    Units: Subjects
        Female
    		 43 43
        Male
    		 47 47
    Subject analysis sets

    Subject analysis set title
    Safety set (S-set)/ Exposed Subjects
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety population included all randomized subjects who have been exposed to the study medication at least once and consisted of 90 patients. Of the 90 exposed patients, 44 patients (48.9%) were assigned to the placebo-group and 46 (51.1%) received 1,000 UA LAIS® Grass tablets per day

    Subject analysis set title
    Intention-To-Treat-set (ITT-set)/Evaluable Subjects
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Since the primary endpoint of this study was the TCS defined by the addition of the daily symptom and medication scores, the availability of diary data during the grass peak pollen season was the key eligibility criterion. Patients not having filled in any patient diary card were only be evaluated in the safety analysis set. Therefore, eight patients of the 90 randomized subjects were not allocated into the ITT-set. In the study protocol was determined that in the case of missing data the Last-Value-Carry-Forward-Option had to be applied. Data missing at the start of the peak pollen season had to be treated as missing data without First-Value-Carry-Backward-Option. However according to the decisions made in the blind data review meeting, for patients with missing diary data on day one of the peak pollen season (and more ahead of the start of the pollen season) and no other baseline assessment of allergy symptoms: the first available data on symptoms and medication use must be assume

    Subject analysis set title
    Per-Protocol-set (PP-set)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients who met all criteria in the protocol and delivered a complete data set of measurements and evaluations of the primary efficacy variable were allocated to the PP-set. As mentioned in the study protocol, a maximum of two successive missing single evaluations of the Rhinoconjunctivitis Total Symptom Score (RTSS) was accepted a per protocol evaluation. Furthermore, the total number of missing single evaluations of the RTSS was not allowed to exceed 25% over the entire course of the peak pollen period. In the blind data review meeting, it was determined that patients having started to fill in the diary card later than 22nd of May of 2014 were evaluated in the ITT analysis set. For this reason, 13 patients were not analyzed in the PP-set. Finally, 60 patients were included into the PP-set. Of these, 26 (43.3%) belonged to the placebo group and 34 patients (56.7%) were allocated into the 1,000 UA/d-group

    Subject analysis sets values
    		 Safety set (S-set)/ Exposed Subjects Intention-To-Treat-set (ITT-set)/Evaluable Subjects Per-Protocol-set (PP-set)
    Number of subjects
    90
    82
    60
    Age categorical
    Units: Subjects
        Adults (18-75)
    90
    82
    60
    Age continuous
    Units: years
        median (full range (min-max))
    38.4 (18 to 69)
    38.621 (18 to 69)
    38.16 (18 to 69)
    Gender categorical
    Units: Subjects
        Female
    43
    40
    30
        Male
    47
    42
    30

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo and verum preparations were identical except of the active substances (carbamylated, monomeric allergoids of grass)

    Reporting group title
    LAIS® Grass Tablets
    Reporting group description
    		 The active ingredients of 1,000 UA-LAIS®Grass sublingual tablets were carbamylated, monomeric allergoids consisting of timothy grass (Phleum pratense), common meadow grass (Poa pratensis) and meadow soft grass (Holcus lanatus) in equal parts. Excipients were lactose, mycrocrystalline cellulosa, silica dioxide and magnesium stearate for each tablet

    Subject analysis set title
    Safety set (S-set)/ Exposed Subjects
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety population included all randomized subjects who have been exposed to the study medication at least once and consisted of 90 patients. Of the 90 exposed patients, 44 patients (48.9%) were assigned to the placebo-group and 46 (51.1%) received 1,000 UA LAIS® Grass tablets per day

    Subject analysis set title
    Intention-To-Treat-set (ITT-set)/Evaluable Subjects
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Since the primary endpoint of this study was the TCS defined by the addition of the daily symptom and medication scores, the availability of diary data during the grass peak pollen season was the key eligibility criterion. Patients not having filled in any patient diary card were only be evaluated in the safety analysis set. Therefore, eight patients of the 90 randomized subjects were not allocated into the ITT-set. In the study protocol was determined that in the case of missing data the Last-Value-Carry-Forward-Option had to be applied. Data missing at the start of the peak pollen season had to be treated as missing data without First-Value-Carry-Backward-Option. However according to the decisions made in the blind data review meeting, for patients with missing diary data on day one of the peak pollen season (and more ahead of the start of the pollen season) and no other baseline assessment of allergy symptoms: the first available data on symptoms and medication use must be assume

    Subject analysis set title
    Per-Protocol-set (PP-set)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients who met all criteria in the protocol and delivered a complete data set of measurements and evaluations of the primary efficacy variable were allocated to the PP-set. As mentioned in the study protocol, a maximum of two successive missing single evaluations of the Rhinoconjunctivitis Total Symptom Score (RTSS) was accepted a per protocol evaluation. Furthermore, the total number of missing single evaluations of the RTSS was not allowed to exceed 25% over the entire course of the peak pollen period. In the blind data review meeting, it was determined that patients having started to fill in the diary card later than 22nd of May of 2014 were evaluated in the ITT analysis set. For this reason, 13 patients were not analyzed in the PP-set. Finally, 60 patients were included into the PP-set. Of these, 26 (43.3%) belonged to the placebo group and 34 patients (56.7%) were allocated into the 1,000 UA/d-group

    Primary: TCS 30D Efficacy

    		 Close Top of page
    End point title
    		 TCS 30D Efficacy
    End point description
    The primary parameter was the assessment of the efficacy of the sublingual immunotherapy with the allergoid LAIS®Grass tablets via a Total Combined Score (TCS) taking into account a Rhinoconjunctivitis Total Symptom Score (RTSS) and a Total Rescue Medication Score (TRMS) for the peak of the grass pollen season. The peak pollen season was defined by those 30 consecutive days per centre with the highest local grass pollen counts, starting with at least “moderate” pollen in the nearest pollen count station in that region.
    End point type
    Primary
    End point timeframe
    Grass pollen season of 30 days
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
        arithmetic mean (standard deviation)
    10.04 ( 6.683 )
    9.16 ( 6.995 )
    Statistical analysis title
    		 TCS 30D compare between groups
    Statistical analysis description
    From all individual daily TCS-values a treatment-dependent mean daily TCS for each day of the peak pollen season of 30 days were calculated. The result of the clinical study was considered as clinically meaningful if a reduction in the actively treated group compared with the placebo group of at least 30 % of the TCS AND a reduction of either the RTSS and/or TRMS of 30% was demonstrated AND a clinically meaningful improvement of QoL occured during the peak pollen season.
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.449
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Notes
    [1] - A statistically significant difference between the actively treated group and the placebo group was not demonstrated. The individual mean daily TCS ranged from 0.47 to 23.10 in the placebo group and from 0.07 to 34.07 in the 1,000 UA/d-group. Therefore, a benefit for actively treated patients could not be demonstrated though the TCS for these patients was lower in the first 2 weeks of the pollen peak compared to the placebo patients.

    Secondary: Rhino-conjunctivits Symptom Score (RSS) 30D

    		 Close Top of page
    End point title
    		 Rhino-conjunctivits Symptom Score (RSS) 30D
    End point description
    he daily mean score for “itchy eyes” was 0.98 in the placebo group and 0.84 in the actively treated group (p = 0.300). The daily mean score for “itchy nose” was 0.83 in the placebo group and 0.89 in the 1,000 UA/d-group (p = 0.845). For the symptom “rhinorrhea” the daily mean score in the placebo group amounted to 0.90 versus 0.83 in the 1,000 UA/d-group (p = 0.632). The daily mean score for “sneezing” was 0.91 in the placebo group and 0.96 in the 1.000 UA/d-group (p = 0.791). The symptom “watery eyes” had a daily mean score of 0.71 in the placebo group versus 0.50 in the actively treated group (p = 0.106). The mean score for “nasal congestion” was 0.78 in the placebo versus 0.86 the 1,000 UA/d-group (p = 0.605). None of these differences between the two treatment groups were statistically significant.
    End point type
    Secondary
    End point timeframe
    Peak Grass Pollen Season of 30 Days
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: score
    arithmetic mean (standard deviation)
        Itchy eyes daily mean 30 days
    0.98 ( 0.661 )
    0.84 ( 0.674 )
        Itchy nose daily mean 30 days
    0.83 ( 0.601 )
    0.89 ( 0.674 )
        Rhinorrhea daily mean 30 days
    0.90 ( 0.647 )
    0.83 ( 0.667 )
        Sneezing daily mean 30 days
    0.91 ( 0.647 )
    0.96 ( 0.652 )
        Watery eyes daily mean 30 days
    0.71 ( 0.642 )
    0.50 ( 0.566 )
        Nasal congestion daily mean 30 days
    0.78 ( 0.685 )
    0.86 ( 0.748 )
    Statistical analysis title
    		 Itchy eyes daily mean 30 days
    Comparison groups
    LAIS® Grass Tablets v Placebo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Itchy nose daily mean 30 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.845
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Rhinorrhea daily mean 30 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.632
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Sneezing daily mean 30 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.791
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Watery eyes daily mean 30 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.106
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Nasal congestion daily mean 30 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.605
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval

    Secondary: Rhino-conjunctivits Symptom Score (RSS) 60D

    		 Close Top of page
    End point title
    		 Rhino-conjunctivits Symptom Score (RSS) 60D
    End point description
    For the entire grass pollen season of 60 days, the daily mean score for “itchy eyes” was 0.70 in the placebo group and 0.48 in the actively treated group (p = 0.300). The daily mean score for “itchy nose” was 0.64 in the placebo group and 0.57 in the 1,000 UA/d-group (p = 0.802). For the symptom “rhinorrhea” the daily mean score in the placebo group amounted to 0.68 versus 0.55 in the 1,000 UA/d-group (p = 0.885). The daily mean score for “sneezing” was 0.73 in the placebo group and 0.78 in the 1.000 UA/d-group (p = 0.762). The symptom “watery eyes” had a daily mean score of 0.49 in the placebo group versus 0.22 in the actively treated group (p = 0.250). The mean score for “nasal congestion” was 0.59 in the placebo versus 0.51 the 1,000 UA/d-group (p = 0.491). None of these differences between the two treatment groups were statistically significant
    End point type
    Secondary
    End point timeframe
    the Peak Grass Pollen Season of the Entire Season of 60 Days.
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
    arithmetic mean (standard deviation)
        Itchy eyes Daily mean 60 days
    0.70 ( 0.500 )
    0.71 ( 0.528 )
        Itchy nose Daily mean 60 days
    0.64 ( 0.495 )
    0.69 ( 0.568 )
        Rhinorrhea Daily mean 60 days
    0.68 ( 0.496 )
    0.67 ( 0.543 )
        Sneezing Daily mean 60 days
    0.73 ( 0.500 )
    0.78 ( 0.552 )
        Watery eyes Daily mean 60 days
    0.49 ( 0.444 )
    0.40 ( 0.463 )
        Nasal congestion Daily mean 60 days
    0.59 ( 0.532 )
    0.68 ( 0.603 )
    Statistical analysis title
    		 Itchy eyes Daily mean 60 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Itchy nose Daily mean 60 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.802
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Rhinorrhea Daily mean 60 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.885
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Sneezing Daily mean 60 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.762
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Watery eyes Daily mean 60 days
    Comparison groups
    LAIS® Grass Tablets v Placebo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.25
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 Nasal congestion daily mean 60 days
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.491
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval

    Secondary: TCS Entire Grass Pollen Season of 60 Days (ITT-set)

    		 Close Top of page
    End point title
    		 TCS Entire Grass Pollen Season of 60 Days (ITT-set)
    End point description
    The daily mean TCS for the 60 day period was 7.34 in the placebo group and 7.24 in the actively treated group. This difference was not stastically significant (p = 0.727). In the placebo group, minimum TCS was 0.98 and maximum was 20.35. In the actively treated group, minimum TCS was 0.05 and maximum was 31.23 . The course of the daily mean TCS in the pollen season of 60 days was similar in the actively treated group compared to the placebo group (Figure 11.1).
    End point type
    Secondary
    End point timeframe
    Entire Grass Pollen Season of 60 Days
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: score
        arithmetic mean (standard deviation)
    7.34 ( 5.157 )
    7.24 ( 6.192 )
    Statistical analysis title
    		 TCS 60D
    Comparison groups
    LAIS® Grass Tablets v Placebo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.727
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Notes
    [2] - The course of the daily mean TCS in the pollen season of 60 days was similar in the actively treated group compared to the placebo group

    Secondary: RTSS for the Entire Grass Pollen Season (ITT-set)

    		 Close Top of page
    End point title
    		 RTSS for the Entire Grass Pollen Season (ITT-set)
    End point description
    The daily mean RTSS for the entire grass pollen season of 60 days amounted to 3.83 in the placebo group versus 3.84 in the 1,000 UA/d-group. The difference between the two groups was statistically not significant (p = 0.791). The daily RTSS ranged from 0.28 points to 10.28 points in the placebo group and from 0.05 to 14.73 points in the 1,000 UA/d-group
    End point type
    Secondary
    End point timeframe
    Entire grass pollen season of 60 days.
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
        arithmetic mean (standard deviation)
    3.83 ( 2.303 )
    3.84 ( 2.801 )
    Statistical analysis title
    		 RTSS Entire Grass Pollen Season (ITT-set)
    Statistical analysis description
    The daily mean RTSS for the entire grass pollen season of 60 days amounted to 3.83 in the placebo group versus 3.84 in the 1,000 UA/d-group. The difference between the two groups was statistically not significant (p = 0.791). The daily RTSS ranged from 0.28 points to 10.28 points in the placebo group and from 0.05 to 14.73 points in the 1,000 UA/d-group.
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.791
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval

    Secondary: TRMS Entire Grass Pollen Season (ITT-set)

    		 Close Top of page
    End point title
    		 TRMS Entire Grass Pollen Season (ITT-set)
    End point description
    The daily mean TRMS for the entire grass pollen season of 60 days was 3.51 in the placebo group and 3.40 in the 1,000 UA/d-group without a statistically significant difference (p = 0.612). The score ranged from 0 to 14.98 points in the placebo group and from 0 to 16.50 points in the 1,000 UA/d-group.
    End point type
    Secondary
    End point timeframe
    Entire Grass Pollen Season 60days
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
        arithmetic mean (standard deviation)
    3.51 ( 3.482 )
    3.40 ( 4.074 )
    Statistical analysis title
    		 TRMS 60D
    Comparison groups
    LAIS® Grass Tablets v Placebo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.612
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval

    Secondary: Reduction of RSS and RCAT

    		 Close Top of page
    End point title
    		 Reduction of RSS and RCAT
    End point description
    The mean retrospective RTSS for the preceeding pollen season 2013 was 13.13 for the placebo and 13.39 for the 1,000 UA/day group. During the entire pollen season 2014 the RTSS decreased to 3.83 in the placebo and 3.84 in the 1,000 UA/d group. For both treatment groups, the difference between the retrospective RTSS and the RTSS was statistically significant (p<0.001) Comparing the difference of the retrospective RTSS of the year 2013 and the RTSS of 2014 between the two treatment groups, stastical significance was not detected (p = 0.809) The rhinitis symptom control was compared between both treatment groups using RCAT at V6. the RCAT scores ranged from 6 to 30. Higher scores indicated better rhinitis control. In the placebo group, the mean RCAT score was 19.18 compared to 20.48 in the 1,000 UA/d-group demonstrating similar rhinitis control in both groups (Table 14.1.4.4.1). The difference between the two treatment groups was statistically not significant significant (p=0.165)
    End point type
    Secondary
    End point timeframe
    pollen season 2013 - pollen season 2014 : At V0 a retrospective RTSS for the preceding grass pollen season 2013 was evaluated for comparison with the RTSS for the upcoming pollen season 2014.
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
    arithmetic mean (standard deviation)
        RTSS D(2013-2014)
    9.30 ( 2.886 )
    9.55 ( 2.810 )
        RCAT
    19.18 ( 3.618 )
    20.48 ( 3.274 )
    Statistical analysis title
    		 RTSS D(2013-2014)
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.809
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 RCAT
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.165
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval

    Secondary: Allergic Severity S

    		 Close Top of page
    End point title
    		 Allergic Severity S
    End point description
    Regarding the conjunctival provocation test, there was a distinct improvement in the allergic severity S between baseline and V4 in each of the two treatment groups, respectively. In the placebo group the allergic severity S improved from 0.58 at baseline to 0.15 at V4. This improvement within the placebo group was statistically significant (p < 0.05). In the 1,000 UA/d-group the allergic severity S improved from 0.40 at baseline to 0.04 at V4. However, this improvement was not statistically significant (p = 0.234). Comparing the placebo group with the 1,000 UA/d-group, the difference in delta allergic severity S (baseline to V4) was not statistically significant (p = 0.201)
    End point type
    Secondary
    End point timeframe
    etween Baseline and Visit V4
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
        arithmetic mean (standard deviation)
    0.15 ( 0.705 )
    0.04 ( 0.564 )
    Statistical analysis title
    		 Allergic Severity S D(Baseline-V4)
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.201
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval

    Secondary: Threshold Allergen Concentration

    		 Close Top of page
    End point title
    		 Threshold Allergen Concentration
    End point description
    The CPT was considered positive if the response was stage 2 or higher. The test was finished after a positive result and no further allergen solutions were applied. Regarding that a higher threshold for a positive CPT meant a lower allergic reactivity, a negative reaction in the CPT was labeled as “0”. A positive reaction at the highest threshold of 10,000 SQ-E/ml was labeled as “1”, a positive reaction at the threshold of 1,000 SQ-E/ml as “2” and positive reaction at the threshold of 100 SQ-E/ml as “3”. CPT result score: 0 = no reaction at any allergen concentration 1 = positive reaction at 10,000 SQ-E/ml 2 = positive reaction at 1,000 SQ-E/ml 3 = positive reaction at 100 SQ-E/ml The CPT result score represented the basis for the calculation of the change of the threshold allergen concentration for a positive response within the CPT between baseline and V4.
    End point type
    Secondary
    End point timeframe
    From Baseline to V4
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
        arithmetic mean (standard deviation)
    0.37 ( 1.125 )
    0.11 ( 0.970 )
    Statistical analysis title
    		 CPT Results between the Two Groups (ITT-set)
    Statistical analysis description
    The change of the threshold allergen concentration for a positive CPT was numerally described by means of the CPT result score. In the placebo group, the score decreased from 1.50 at baseline to 1.12 at visit 4. The difference was 0.37. In the 1,000 UA/d-group, the CPT result score declined from 1.23 at baseline to 1.11 at visit 4. The difference was 0.11. The decrease in the CPT result score between baseline and visit 4 in each treatment group was statistically not significant
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.237
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Notes
    [3] - Comparing the difference of the CPT result score between baseline and visit 4 between the two treatment groups, this was also not statistically significant (p=0.237)

    Secondary: Redness of the Eye

    		 Close Top of page
    End point title
    		 Redness of the Eye
    End point description
    Previous to the provocation, the status of the eye was documented by photography and used as baseline. Afterwards, one eye of the patient was challenged with the test solution containing grass allergens while the other eye was treated with control solution. 10 minutes after applying each of the solutions, photographies of the eyes were taken again. This procedure was continued until a CPT response of stage 2 had occurred. The reddness of the conjunctiva of each patient was rated by two independent observers using the following scale. In analogy to allergic severity S, the redness of the eye was depicted by a composite score (CS)
    End point type
    Secondary
    End point timeframe
    From baseline to V4
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
    arithmetic mean (standard deviation)
        Delta Th(Red) Baseline V4
    -0.04 ( 1.224 )
    -0.41 ( 1.500 )
        Delta CS bl-V4
    0.04 ( 0.776 )
    -0.11 ( 0.365 )
    Statistical analysis title
    		 Delta Th(Red) Baseline V4
    Statistical analysis description
    Redness of the eye was assessed by a central observer. At baseline, the threshold score of the redness of the eye was 1.53 in the placebo and 1.05 in the actively treated group. At V4, the threshold score increased to 1.63 and 1.53 in the placebo and 1,000 UA/day group, respectively. This indicated a reddening of the conjunctiva at an allergene challenge in the range of 1,000 to 10,000 SQ-E/ml in the CPT.
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.263
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Notes
    [4] - The difference between baseline and V4 was -0.04 in the placebo group and -0.41 in the actively treated group, respectively. Statistical significance was not detected neither comparing threshold at baseline and visit 4 in each treatment group nor comparing both treatment groups according to the difference of the threshold between baseline and visit 4.
    Statistical analysis title
    		 Delta CS
    Statistical analysis description
    Delta Composite Score Baseline – V4 between the two treatment groups
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.162
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Notes
    [5] - The mean composite score (CS) changed from 0.35 at baseline to 0.36 at visit 4 in the placebo group. In the actively treated group, the mean CS increased from 0.20 at baseline to 0.30 at visit 4. These changes were not statistically significant. Comparing delta CS baseline – visit 4 between the two treatment groups, this was also not statistically significant.

    Secondary: Well Days

    		 Close Top of page
    End point title
    		 Well Days
    End point description
    The number of well days defined as days with a maximum symptom score of 2 and no rescue medication use. Well Days Mean within 60 Days was compared between the 2 Treatment Groups
    End point type
    Secondary
    End point timeframe
    Entire Grass Pollen Season of 60 Days
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
    arithmetic mean (standard deviation)
        Mean Number of Well days
    27.32 ( 16.369 )
    25.77 ( 17.619 )
    Statistical analysis title
    		 Well Days Compare between Groups
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.593
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Notes
    [6] - The number of well days defined as days with a maximum symptom score of 2 and no rescue medication use ranged between 0 and 56 days in the placebo group and 0 to 60 days in the 1,000 UA/day group. The mean number of well days was 27.32 in the placebo group and 25.77 in the actively treated group. The difference between the two treatment groups was statistically not significant (p = 0.593)

    Secondary: IgG4

    		 Close Top of page
    End point title
    		 IgG4
    End point description
    Blood sampling for the measurement of grass pollen specific IgG4 was performed before and after treatment. Delta Grass Pollen Specific IgG4 was compared between the Two Treatment Groups.
    End point type
    Secondary
    End point timeframe
    Entire grass pollen season of 60 days
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
    arithmetic mean (standard deviation)
        Delta IgG4
    -0.01 ( 0.338 )
    -0.04 ( 0.265 )
    Statistical analysis title
    		 Delta IgG4 before and after treament
    Comparison groups
    LAIS® Grass Tablets v Placebo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.627
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval

    Secondary: Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)

    		 Close Top of page
    End point title
    		 Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
    End point description
    The patients were asked to fill in the RQLQ at V1, V5, V6 and V7. With this questionnaire, the problems which adults with rhinoconjunctivitis experienced during the study were measured. It had 28 questions in seven domains: activity limitations sleep impairment, non-nasal/eye symptoms, practical problems, nasal symptoms, eye symptoms and emotional problems.
    End point type
    Secondary
    End point timeframe
    From V1 to V7
    End point values
    		 Placebo LAIS® Grass Tablets
    Number of subjects analysed
    38
    44
    Units: Score
    arithmetic mean (standard deviation)
        RQLQ Score V1
    1.04 ( 0 )
    0.80 ( 0 )
        RQLQ Score V5
    1.44 ( 1.263 )
    1.22 ( 0.948 )
        RQLQ Score V6
    1.78 ( 1.051 )
    1.58 ( 1.093 )
        RQLQ Score V7
    0.43 ( 1.135 )
    0.63 ( 1.176 )
    Statistical analysis title
    		 RQLQ Comparing the Global Score V1
    Statistical analysis description
    The global score considering all subscores of the seven domains was calculated at V1. Comparing both treatment groups, there was no statistical significance. Similarly, the subscores of the seven domains exhibited neither statistically significant differences nor numerical differences (i.e. more than 0.5 points) with clinical relevance between the treatment groups.
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.791
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 RQLQ Comparing the Global Score V5
    Statistical analysis description
    The global score considering all subscores of the seven domains was calculated at V5. Comparing both treatment groups, there was no statistical significance. Similarly, the subscores of the seven domains exhibited neither statistically significant differences nor numerical differences (i.e. more than 0.5 points) with clinical relevance between the treatment groups.
    Comparison groups
    LAIS® Grass Tablets v Placebo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.273
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 RQLQ Comparing the Global Score V6
    Statistical analysis description
    The global score considering all subscores of the seven domains was calculated at V6. Comparing both treatment groups, there was no statistical significance. Similarly, the subscores of the seven domains exhibited neither statistically significant differences nor numerical differences (i.e. more than 0.5 points) with clinical relevance between the treatment groups.
    Comparison groups
    Placebo v LAIS® Grass Tablets
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.281
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval
    Statistical analysis title
    		 RQLQ Comparing the Global Score V7
    Statistical analysis description
    The global score considering all subscores of the seven domains was calculated at V7 Comparing both treatment groups, there was no statistical significance. Similarly, the subscores of the seven domains exhibited neither statistically significant differences nor numerical differences (i.e. more than 0.5 points) with clinical relevance between the treatment groups.
    Comparison groups
    LAIS® Grass Tablets v Placebo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.281
    Method
    		 Asymp. Sig. (2-tailed)
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    observation period between V1 and V7.
    Adverse event reporting additional description
    37 patients reported a total number of 61 treatment emergent adverse events (TEAEs) which occurred during the observation period between V1 and V7. Two serious adverse events were reported , which were not related to the intake of study medication.Neither fatality nor anaphylactic reaction which would have required the use of epinephrine occurred.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    safety-set
    Reporting group description
    		 -

    Serious adverse events
    		 safety-set
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 90 (2.22%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Ligament rupture
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Road traffic accident
    Additional description: road traffic accident with traumatic brain injuries
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 safety-set
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    37 / 90 (41.11%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Haemorrhage
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Surgical and medical procedures
    Cerumen removal
         subjects affected / exposed
    2 / 90 (2.22%)
         occurrences all number
    2
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Nasal dryness
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Rhinitis allergic
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Epistaxis
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Sneezing
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Cough
         subjects affected / exposed
    2 / 90 (2.22%)
         occurrences all number
    2
    Asthma
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Bronchospasm
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Psychiatric disorders
    Mental disorder due to a general condition
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Investigations
    Laboratory test abnormal
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Sports injury
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Craniocerebral injury
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Skull fractured base
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 90 (3.33%)
         occurrences all number
    3
    Eye disorders
    Eye pruritus
         subjects affected / exposed
    2 / 90 (2.22%)
         occurrences all number
    2
    Eye inflammation
         subjects affected / exposed
    2 / 90 (2.22%)
         occurrences all number
    2
    Conjunctivitis allergic
         subjects affected / exposed
    2 / 90 (2.22%)
         occurrences all number
    2
    Ocular hyperaemia
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Blepharitis
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Paresthesia oral
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Tongue coated
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Oral pruritus
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Rash
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Foot deformity
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Back pain
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Arthralgia
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Pain in extremity
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Infections and infestations
    Chlamydial infection
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Nasopharyngitis
         subjects affected / exposed
    3 / 90 (3.33%)
         occurrences all number
    6
    Conjunctivitis bacterial
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Tonsillitis
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Sinusitis
         subjects affected / exposed
    2 / 90 (2.22%)
         occurrences all number
    2
    Otitis externa
         subjects affected / exposed
    2 / 90 (2.22%)
         occurrences all number
    2
    Otasalpingitis
         subjects affected / exposed
    2 / 90 (2.22%)
         occurrences all number
    2
    Infection
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Otitis media
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    3 / 90 (3.33%)
         occurrences all number
    3
    Rhinitis
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 90 (1.11%)
         occurrences all number
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Mar 2013
    Changes implemented by reason of deficiency letter of PEI
    19 Jun 2013
    Postponement of study
    20 Nov 2013
    Component resolved diagnostics in allergy diagnostics (RAST) was implemented
    07 May 2014
    Adaptation of the visit schedule required to the extension of the inclusion period,

    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.
    The need to amend the trial from pre-seasonal treatment phase of 20 weeks to pre-/co-seasonal treatment with 9 to 12 weeks. The overall duration of the intake of study medication still was 20 weeks.
    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-Sun May 05 17:20:28 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA