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:
    An open, randomised, clinical trial parallel-controlled with Mycostatin oral suspension, evaluating the efficacy of Nystatin oral gel and Nystatin oral suspension in adult patients with oropharyngeal candidiasis.

    Summary
    EudraCT number
    		 2013-003784-56
    Trial protocol
    		 CZ  
    Global end of trial date
    17 Dec 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Jun 2022
    First version publication date
    16 Jun 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NV012013
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    VUAB Pharma a.s.
    Sponsor organisation address
    Vltavská 53, Roztoky, Czechia, 25263
    Public contact
    Klára Kynčlová, VUAB Pharma a.s., +420 733 695 601, kkynclova@vuab.cz
    Scientific contact
    Klára Kynčlová, VUAB Pharma a.s., +420 733 695 601, kkynclova@vuab.cz
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    09 Mar 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    17 Dec 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Dec 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Evaluation of the efficacy of Nystatin oral gel and Nystatin oral suspension compared to the reference medical product with the same active ingredient (nystatinum) in oral suspension form. Note: This clinical trial was conducted as pilot one and its outcomes will be used for another clinical trial to confirm preliminary results of this trial.
    Protection of trial subjects
    Oral administration did not require any specific measures to minimise pain and distress of trial subjects.
    Background therapy
    		 None
    Evidence for comparator
    		 The products Nystatin oral gel and Nystatin oral suspension are generic and their efficacy compliance with similar products containing the same active ingredient had to be demonstrated by a comparative study in accordance with article 10.3 of Directive 2001/83/ES. As a reference medication (comparator), Mycostatin oral suspension (Bristol-Myers Squibb Pharmaceutical Limited, the holder of authorization) was chosen, which contains the nystatin as the active substance. No nystatin oral gel with suitable dossier was found in European Union countries. Therefore, Mycostatin oral suspension having suitable dossier confirmed by the Spain authority was chosen as the reference medication for both test investigational products (suspension and gel) in accordance with legislation.
    Actual start date of recruitment
    24 Apr 2014
    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
    Czechia: 90
    Worldwide total number of subjects
    90
    EEA total number of subjects
    90
    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)
    90
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects were approached for participation by investigators. Participation in the clinical trial was offered to all patients with oropharyngeal candidiasis visiting an otorhinolaryngology or allergology/immunology specialist. The recruitment was performed during study period (from April 2014 to November 2014) in the Czech republic.

    Pre-assignment
    Screening details
    		 The investigator assessed clinical finding by physical examination – the count and extension of lesions as well as extension of erythema, thrush, and mucositis in mouth, including swab sample for laboratory confirmation.

    Pre-assignment period milestones
    Number of subjects started
    		 90
    Number of subjects completed
    		 90

    Period 1
    Period 1 title
    Treatment (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    None

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nystatin suspension
    Arm description
    		 The enrolled subjects used this test investigational product during 28 days of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nystatin 100,000 IU/ml oral suspension
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oromucosal use, Buccal use, Oropharyngeal use
    Dosage and administration details
    For study purposes, it was specified the dose of 5.0 ml of suspension at the concentration of 100.000 U/ml. It was required to apply one dose twice a day in interval of about 12 hours. The subject was instructed to leave the investigational product in the affected area for at least 1 minute to achieve the desired effect. The subject was enabled to swallow both forms of investigational product. The investigational product had always to be applied after meals. The suspension dose, which was shaken in the bottle before administration, had to be measured using a calibrated plastic syringe. The content of the syringe was administered in the mouth. The suspension was kept in the mouth for at least 1 minute before swallowing.

    Arm title
    		 Nystatin gel
    Arm description
    		 The enrolled subjects used this test investigational product during 28 days of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nystatin 100,000 IU/ml oral gel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral gel
    Routes of administration
    Buccal use, Oromucosal use, Oropharyngeal use
    Dosage and administration details
    For study purposes, it was specified the dose of 5.0 ml of gel at the concentration of 100.000 U/g. It was required to apply one dose twice a day in interval of about 12 hours. The subject was instructed to leave the investigational product in the affected area for at least 1 minute to achieve the desired effect. The subject was enabled to swallow both forms of investigational product. The investigational product had always to be applied after meals. The gel dose had to be measured on the calibrated spoon, i.e., the study dose represented the amount of gel up to mark 5. The gel was applied with a finger from the spoon into the mouth. It was applied on the affected and surrounding areas. It had to be left to act for at least 1 minute and then swallowed.

    Arm title
    		 Mycostatin suspension
    Arm description
    		 The enrolled subjects used this reference product during 28 days of treatment.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    MYCOSTATIN 100,000 IU/ml
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Buccal use, Oromucosal use, Oropharyngeal use
    Dosage and administration details
    For study purposes, it was specified the dose of 5.0 ml of suspension at the concentration of 100.000 U/ml. It was required to apply one dose twice a day in interval of about 12 hours. The subject was instructed to leave the investigational product in the affected area for at least 1 minute to achieve the desired effect. The subject was enabled to swallow both forms of investigational product. The investigational product had always to be applied after meals. The suspension dose, which was shaken in the bottle before administration, had to be measured using a calibrated plastic syringe. The content of the syringe was administered in the mouth. The suspension was kept in the mouth for at least 1 minute before swallowing.

    Number of subjects in period 1
    		Nystatin suspension Nystatin gel Mycostatin suspension
    Started
    30
    30
    30
    Completed
    30
    30
    30

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Nystatin suspension
    Reporting group description
    		 The enrolled subjects used this test investigational product during 28 days of treatment.

    Reporting group title
    Nystatin gel
    Reporting group description
    		 The enrolled subjects used this test investigational product during 28 days of treatment.

    Reporting group title
    Mycostatin suspension
    Reporting group description
    		 The enrolled subjects used this reference product during 28 days of treatment.

    Reporting group values
    		 Nystatin suspension Nystatin gel Mycostatin suspension Total
    Number of subjects
    		 30 30 30 90
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 30 30 30 90
        From 65-84 years
    		 0 0 0 0
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 48 (21 to 60) 42 (19 to 59) 44 (25 to 58) -
    Gender categorical
    Units: Subjects
        Female
    		 22 18 15 55
        Male
    		 8 12 15 35
    Subject analysis sets

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    It represented all subjects regardless of Candida albicans load at treatment start or the study medication consumption.

    Subject analysis set title
    PPS
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The PPS set (per protocol set) included of ITT set: • subjects were not withdrawn from the study • subjects with known laboratory result for each visit • subjects with mycological score ≥2 at start of treatment

    Subject analysis sets values
    		 ITT PPS
    Number of subjects
    90
    61
    Age categorical
    Units: Subjects
        In utero
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    0
    0
        Adults (18-64 years)
    90
    61
        From 65-84 years
    0
    0
        85 years and over
    0
    0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    45 (19 to 60)
    41 (21 to 60)
    Gender categorical
    Units: Subjects
        Female
    55
    42
        Male
    35
    19

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Nystatin suspension
    Reporting group description
    		 The enrolled subjects used this test investigational product during 28 days of treatment.

    Reporting group title
    Nystatin gel
    Reporting group description
    		 The enrolled subjects used this test investigational product during 28 days of treatment.

    Reporting group title
    Mycostatin suspension
    Reporting group description
    		 The enrolled subjects used this reference product during 28 days of treatment.

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    It represented all subjects regardless of Candida albicans load at treatment start or the study medication consumption.

    Subject analysis set title
    PPS
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The PPS set (per protocol set) included of ITT set: • subjects were not withdrawn from the study • subjects with known laboratory result for each visit • subjects with mycological score ≥2 at start of treatment

    Primary: mycological cure rate (ITT)

    		 Close Top of page
    End point title
    		 mycological cure rate (ITT)
    End point description
    End point type
    Primary
    End point timeframe
    Treatment
    End point values
    		 Nystatin suspension Nystatin gel Mycostatin suspension ITT
    Number of subjects analysed
    30
    30
    30
    90
    Units: Total
    24
    23
    22
    69
    Statistical analysis title
    		 difference: Nystatin suspension - Mycostatin (ITT)
    Statistical analysis description
    The two-sided confidence interval of difference between two proportions/rates was calculated as simple asymptotic.
    Comparison groups
    Mycostatin suspension v Nystatin suspension
    Number of subjects included in analysis
    60
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 > 0.05
    Method
    		 Fisher exact
    Parameter type
    		 Risk difference (RD)
    Point estimate
    6.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.7
         upper limit
    		 28
    Statistical analysis title
    		 difference: Nystatin gel - Mycostatin (ITT)
    Comparison groups
    Nystatin gel v Mycostatin suspension
    Number of subjects included in analysis
    60
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 > 0.05
    Method
    		 Fisher exact
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.3
         upper limit
    		 12.3

    Secondary: mycological cure rate (PPS)

    		 Close Top of page
    End point title
    		 mycological cure rate (PPS)
    End point description
    The primary endpoint defined by the protocol was the mycological cure rate as a proportion of subjects who achieved mycological score <2 (i.e., mycological finding ≤5 CFU/swab) after study treatment.
    End point type
    Secondary
    End point timeframe
    Treatment
    End point values
    		 Nystatin suspension Nystatin gel Mycostatin suspension PPS
    Number of subjects analysed
    21
    20
    20
    61
    Units: Total
    17
    13
    16
    46
    Statistical analysis title
    		 difference: Nystatin suspension - Mycostatin (PPS)
    Statistical analysis description
    The two-sided confidence interval of difference between two proportions/rates was calculated as simple asymptotic.
    Comparison groups
    Mycostatin suspension v Nystatin suspension
    Number of subjects included in analysis
    41
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 > 0.05
    Method
    		 Fisher exact
    Parameter type
    		 Risk difference (RD)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.3
         upper limit
    		 25.2
    Statistical analysis title
    		 difference: Nystatin gel - Mycostatin (PPS)
    Statistical analysis description
    The two-sided confidence interval of difference between two proportions/rates was calculated as simple asymptotic.
    Comparison groups
    Nystatin gel v Mycostatin suspension
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 > 0.05
    Method
    		 Fisher exact
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.3
         upper limit
    		 12.3

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events included close vigilance for reporting of reactions about 4-week treatment, as well as measurement of vital signs.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    10
    Reporting groups
    Reporting group title
    Nystatin suspension
    Reporting group description
    		 The enrolled subjects used this test investigational product during 28 days of treatment.

    Reporting group title
    Nystatin gel
    Reporting group description
    		 The enrolled subjects used this test investigational product during 28 days of treatment.

    Reporting group title
    Mycostatin suspension
    Reporting group description
    		 The enrolled subjects used this test investigational product during 28 days of treatment.

    Serious adverse events
    		 Nystatin suspension Nystatin gel Mycostatin suspension
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (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
    		 Nystatin suspension Nystatin gel Mycostatin suspension
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 30 (23.33%)
    11 / 30 (36.67%)
    4 / 30 (13.33%)
    Social circumstances
    Taste disorder
    Additional description: unpleasant taste
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 30 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    2
    1
    Application site discomfort
    Additional description: unsatisfactory application
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 30 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    0
    2
    0
    Gastrointestinal disorders
    Burning sensation
    Additional description: mouth or gums burning
         subjects affected / exposed
    3 / 30 (10.00%)
    4 / 30 (13.33%)
    0 / 30 (0.00%)
         occurrences all number
    3
    4
    0
    Tongue disorder
    Additional description: tongue tingling, tongue burning
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    1
    0
    Nausea
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    1
    Skin and subcutaneous tissue disorders
    Rash
    Additional description: rash on the hands
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    0
    1
    Infections and infestations
    Cough
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    1
    0
    1
    Viral infection
    Additional description: unspecified virosis/cold
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    0
    1
    0

    More information

    		 Close Top of page

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

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

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

    European Medicines Agency © 1995-Sat May 04 15:43:40 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA