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   43872   clinical trials with a EudraCT protocol, of which   7291   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:
    Phase III study to evaluate the efficacy of a novel antimycotic vaginal pessary combination (containing Benzydamine HCl 6 mg and Econazole nitrate 150 mg) in the Treatment of uncomplicated vulvovaginal candidosis (VVC) [BEtreat study]

    Summary
    EudraCT number
    		 2016-002808-19
    Trial protocol
    		 BG   PL   IT  
    Global end of trial date
    02 Apr 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Apr 2019
    First version publication date
    17 Apr 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    030(4C)HO16241
    Additional study identifiers
    ISRCTN number
    		 ISRCTN00000000
    US NCT number
    		 NCT00000000
    WHO universal trial number (UTN)
    		 U0000-0000-0000
    Sponsors
    Sponsor organisation name
    Aziende Chimiche Riunite Angelini Francesco- A.C.R.A.F. S.p.A.
    Sponsor organisation address
    Piazzale della Stazione s.n.c., S.Palomba-Pomezia (Rome), Italy, 00071
    Public contact
    A.C.R.A.F. HQMD Clinical Operations , Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A, +39 06 91045364, a.bonelli@angelini.it
    Scientific contact
    A.C.R.A.F. HQMD Clinical Operations , Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A, +39 06 91045364, a.bonelli@angelini.it
    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
    02 Apr 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Apr 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Apr 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the microbiological and clinical efficacy, the safety and acceptability of the benzydamine HCl 6 mg and econazole nitrate 150 mg vaginal pessary, in comparison to Pevaryl® 150 mg vaginal pessary, in the treatment of uncomplicated VVC.
    Protection of trial subjects
    No specific measures are provided. In case of ineffective treatment the Investigator can administer alternative drugs and the patients discontinue study.
    Background therapy
    		 Not applicable
    Evidence for comparator
    		 Pevaryl® 150 mg (Pevaryl®, Janssen Cilag S.p.A.), pessary was selected as Comparator because it represented the drug of choice authorized for the treatment of uncomplicated VVC. The dosage regimen of Pevaryl® 150 mg vaginal pessary to be administered to the patients was consistent with that reported in the relevant Summary of Product Characteristics (SmPC).
    Actual start date of recruitment
    06 Oct 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Russian Federation: 183
    Country: Number of subjects enrolled
    Poland: 66
    Country: Number of subjects enrolled
    Bulgaria: 188
    Country: Number of subjects enrolled
    Italy: 8
    Worldwide total number of subjects
    445
    EEA total number of subjects
    262
    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)
    445
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment of 440 (220 per treatment group) patients was planned. 445 (222 in benzydamine HCl / econazole group; 223 in Pevaryl® group) were randomised and received the study medication starting from 6 October 2017 to 2 April 2018.

    Pre-assignment
    Screening details
    		 456 patients were evaluated for elegibility. 11 patients were excluded and defined Screening Failures.

    Period 1
    Period 1 title
    PERIOD 1 (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    The study was performed in double blind conditions, consequently, during the study, neither the Investigator nor the patient were aware of the treatment assigned. Despite the impossibility of masking the marketed Comparator due to reasons related to the manufacturing process, the double-blind condition was guaranteed introducing a second clinical staff member who acted as drug-administrator. Accordingly, the Investigator acted as assessor, blinded to the drug administered to the patient.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg
    Arm description
    		 Benzydamine HCl 6 mg / Econazole nitrate 150 mg pessary, intravaginal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Benzydamine HCl 6 mg / econazole nitrate 150 mg
    Investigational medicinal product code
    030(C)
    Other name
    Pharmaceutical forms
    Pessary
    Routes of administration
    Vaginal use
    Dosage and administration details
    1 pessary once daily for 3 consecutive days

    Arm title
    		 Reference: ECONAZOLE 150 mg
    Arm description
    		 Econazole 150 mg pessary (Pevaryl®, Janssen Cilag S.p.A.), intravaginal.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Econazole
    Investigational medicinal product code
    Other name
    Pevaryl®
    Pharmaceutical forms
    Pessary
    Routes of administration
    Vaginal use
    Dosage and administration details
    1 pessary once daily for 3 consecutive days

    Number of subjects in period 1
    		Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Started
    222
    223
    Completed
    222
    223

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Test: BNZ 6 mg / ECONAZOLE 150 mg
    Reporting group description
    		 Benzydamine HCl 6 mg / Econazole nitrate 150 mg pessary, intravaginal.

    Reporting group title
    Reference: ECONAZOLE 150 mg
    Reporting group description
    		 Econazole 150 mg pessary (Pevaryl®, Janssen Cilag S.p.A.), intravaginal.

    Reporting group values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg Total
    Number of subjects
    		 222 223 445
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 222 223 445
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 222 223 445
        Male
    		 0 0 0
    Subject analysis sets

    Subject analysis set title
    Safety analysis
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety population (SP) was defined as all randomized patients who took at least one dose of the study medication.

    Subject analysis set title
    Modified Intention-to-Treat (m-ITT)
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Modified Intention-to-Treat (m-ITT) population was defined as all randomized patients with signs score ≥1 and symptoms score ≥3 at Visit 0, who took at least one dose of the study medications and performed the microbiological evaluation at Visit 3 (if applicable), or at Visit 4 (TOC), or at ETV/ETTV, and having at least one-post baseline clinical evaluation of symptoms.

    Subject analysis set title
    Per Protocol (PP) population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Per Protocol (PP) population: the patients from the m-ITT population with no major protocol violations.

    Subject analysis sets values
    		 Safety analysis Modified Intention-to-Treat (m-ITT) Per Protocol (PP) population
    Number of subjects
    445
    443
    420
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
        Adults (18-64 years)
    445
    443
    420
        From 65-84 years
    0
    0
    0
        85 years and over
    0
    0
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    445
    443
    420
        Male
    0
    0
    0

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Test: BNZ 6 mg / ECONAZOLE 150 mg
    Reporting group description
    		 Benzydamine HCl 6 mg / Econazole nitrate 150 mg pessary, intravaginal.

    Reporting group title
    Reference: ECONAZOLE 150 mg
    Reporting group description
    		 Econazole 150 mg pessary (Pevaryl®, Janssen Cilag S.p.A.), intravaginal.

    Subject analysis set title
    Safety analysis
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety population (SP) was defined as all randomized patients who took at least one dose of the study medication.

    Subject analysis set title
    Modified Intention-to-Treat (m-ITT)
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Modified Intention-to-Treat (m-ITT) population was defined as all randomized patients with signs score ≥1 and symptoms score ≥3 at Visit 0, who took at least one dose of the study medications and performed the microbiological evaluation at Visit 3 (if applicable), or at Visit 4 (TOC), or at ETV/ETTV, and having at least one-post baseline clinical evaluation of symptoms.

    Subject analysis set title
    Per Protocol (PP) population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Per Protocol (PP) population: the patients from the m-ITT population with no major protocol violations.

    Primary: MYCOLOGICAL CURE (m-ITT)

    		 Close Top of page
    End point title
    		 MYCOLOGICAL CURE (m-ITT)
    End point description
    Since the clinical and microbiological endpoints are of equal importance for the overall judgement of efficacy of the Fixed Dose Combination (FDC) containing Benzydamine HCl 6 mg and Econazole nitrate 150 mg vaginal pessary in comparison to Pevaryl® 150 mg vaginal pessary, the clinical (time to first symptoms relief) and microbiological (mycological cure) endpoints have been regarded as co-primary. The first co-primary endpoint was the microbiological response, defined as the absence of Candida or other yeasts at microscopy (mycological cure), at Visit 3, or at Visit 4.
    End point type
    Primary
    End point timeframe
    The time point was Visit 3 - 2 days (+2 days) after EOT (End Of Treatment) or Visit 4 - 7 days (+2 days) after EOT
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    223
    Units: percent
    number (confidence interval 95%)
        Absence of Candida (%)
    94.6 (91.63 to 97.57)
    92.8 (89.34 to 96.18)
    Statistical analysis title
    		 Confidence limits
    Statistical analysis description
    Benzydamine HCl 6 mg and Econazole nitrate 150 mg vaginal pessary would have been considered non-inferior to Pevaryl® 150 mg vaginal pessary if the lower limit of the two-sided 95% Confidence Interval (95% CI) of the difference between the study drugs in the mycological cure rates did not exceed the threshold of -10.0%.
    Comparison groups
    Reference: ECONAZOLE 150 mg v Test: BNZ 6 mg / ECONAZOLE 150 mg
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 6.36

    Primary: CLINICAL RESPONSE (m-ITT)

    		 Close Top of page
    End point title
    		 CLINICAL RESPONSE (m-ITT)
    End point description
    clinical response: time to first relief of symptoms, defined as the earliest time when the sum of the scores for all symptoms declines by 1 point or more with respect to the sum of the scores at baseline
    End point type
    Primary
    End point timeframe
    The time to first relief of symptoms was determined after the first IMP administration, using a specific 4-point scale: 0=absent, 1=mild, 2=moderate, 3=severe.
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    223
    Units: percent
        number (not applicable)
    100
    99.55
    Statistical analysis title
    		 Survival analysis
    Statistical analysis description
    The time to first relief of symptoms was analyzed using the log-rank test, at a two-sided alpha level of 5%. A p-value less than 0.05 was considered statistically significant.
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0042
    Method
    		 Logrank
    Confidence interval

    Primary: MICOLOGYCAL CURE (PP)

    		 Close Top of page
    End point title
    		 MICOLOGYCAL CURE (PP)
    End point description
    Since the clinical and microbiological endpoints are of equal importance for the overall judgement of efficacy of the Fixed Dose Combination (FDC) containing Benzydamine HCl 6 mg and Econazole nitrate 150 mg vaginal pessary in comparison to Pevaryl® 150 mg vaginal pessary, the clinical (time to first symptoms relief) and microbiological (mycological cure) endpoints have been regarded as co-primary. The first co-primary endpoint was the microbiological response, defined as the absence of Candida or other yeasts at microscopy (mycological cure), at Visit 3, or at Visit 4.
    End point type
    Primary
    End point timeframe
    The time point was Visit 3 - 2 days (+2 days) after EOT (End Of Treatment) or Visit 4 - 7 days (+2 days) after EOT
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    221
    Units: percent
        number (confidence interval 95%)
    95.2 (92.32 to 98.11)
    93.4 (90.01 to 96.72)
    Statistical analysis title
    		 Confidence limits
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.58
         upper limit
    		 6.28

    Secondary: Time to total symptoms relief (m-ITT)

    		 Close Top of page
    End point title
    		 Time to total symptoms relief (m-ITT)
    End point description
    The time to total symptoms relief, defined as the time when the sum of the scores for all symptoms becomes 0.
    End point type
    Secondary
    End point timeframe
    The time to total symptoms relief was determined after the first IMP administration, using a specific 4-point scale: 0=absent, 1=mild, 2=moderate, 3=severe.
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    223
    Units: percent
        number (not applicable)
    95.5
    95.02
    Statistical analysis title
    		 Survival analysis
    Statistical analysis description
    The time to first relief of symptoms was analyzed using the log-rank test, at a two-sided alpha level of 5%. A p-value less than 0.05 was considered statistically significant.
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3942
    Method
    		 Logrank
    Confidence interval

    Secondary: Area under the differences from baseline for local burning sensation (m-ITT)

    		 Close Top of page
    End point title
    		 Area under the differences from baseline for local burning sensation (m-ITT)
    End point description
    Changes from Screening/Baseline for local burning sensation of uncomplicated VVC, were assessed as the sum of the difference of the scores at each time point (AUC)
    End point type
    Secondary
    End point timeframe
    From Screening/Baseline until 24 h after the first drug application.
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    223
    Units: AUC
        arithmetic mean (standard deviation)
    42.7 ( 15.2 )
    40.2 ( 16.2 )
    Statistical analysis title
    		 ANOVA
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.072
    Method
    		 ANOVA
    Confidence interval

    Secondary: Area under the differences from baseline for local pain (m-ITT)

    		 Close Top of page
    End point title
    		 Area under the differences from baseline for local pain (m-ITT)
    End point description
    Changes from Screening/Baseline for local pain of uncomplicated VVC, were assessed as the sum of the difference of the scores at each time point (AUC).
    End point type
    Secondary
    End point timeframe
    From Screening/Baseline until 24 h after the first drug application.
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    223
    Units: AUC
        arithmetic mean (standard deviation)
    31.2 ( 19.8 )
    27.7 ( 18.7 )
    Statistical analysis title
    		 ANOVA
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.067
    Method
    		 ANOVA
    Confidence interval

    Secondary: Area under the differences from baseline for local pruritus (m-ITT)

    		 Close Top of page
    End point title
    		 Area under the differences from baseline for local pruritus (m-ITT)
    End point description
    hanges from Screening/Baseline for local pruritus of uncomplicated VVC, were assessed as the sum of the difference of the scores at each time point (AUC)
    End point type
    Secondary
    End point timeframe
    From Screening/Baseline until 24 h after the first drug application.
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    223
    Units: AUC
        arithmetic mean (standard deviation)
    47.3 ( 13.7 )
    43.8 ( 13.9 )
    Statistical analysis title
    		 ANOVA
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.011
    Method
    		 ANOVA
    Confidence interval

    Secondary: Clinical evaluation (cure, improvement and failure) (m-ITT)

    		 Close Top of page
    End point title
    		 Clinical evaluation (cure, improvement and failure) (m-ITT)
    End point description
    Clinical cure, improvement and failure were evaluated on the basis of Investigator’s and patient’s assessement of the objective signs (presence and severity) and subjective symptoms (presence and severity) of uncomplicated VVC, respectively.
    End point type
    Secondary
    End point timeframe
    The time point was at Visit 3 or at ETTV/ETV
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    223
    Units: Number
        CURE
    132
    125
        IMPROVEMENT
    75
    80
        FAILURE
    2
    6
    Statistical analysis title
    		 Chi-squared
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.31
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Therapeutic cure (m-ITT)

    		 Close Top of page
    End point title
    		 Therapeutic cure (m-ITT)
    End point description
    The therapeutic cure, was defined combining mycological eradication (absence of Candida or other yeast at microscopy) and clinical cure (resolution of all signs and symptoms).
    End point type
    Secondary
    End point timeframe
    The time point was at Visit 4 (TOC), or at ETTV/ETV.
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    221
    Units: Number
        CURE
    166
    166
        FAILURE
    52
    45
    Statistical analysis title
    		 Chi-squared
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.532
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Recurrences

    		 Close Top of page
    End point title
    		 Recurrences
    End point description
    Recurrence was defined as the presence of Candida or other yeast at microscopy, at the Follow-up Visit in a patient judged as therapeutically cured at Visit 4 (TOC) who refered a reappearance of the symptomatic disease at the telephonic follow-up.
    End point type
    Secondary
    End point timeframe
    The time point was at the Follow-up Visit .
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    165
    166
    Units: Number
        SUCCESS
    163
    162
        RECURRENCE
    2
    4
    No statistical analyses for this end point

    Secondary: Changes in the total score of symptoms (m-ITT)

    		 Close Top of page
    End point title
    		 Changes in the total score of symptoms (m-ITT)
    End point description
    Percent change in the total score of symptoms from the Screening/Baseline.
    End point type
    Secondary
    End point timeframe
    This endpoint was evaluated at each time point after the first drug application.
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    221
    Units: percent
    arithmetic mean (standard error)
        15 min
    11.55 ( 1.54 )
    10.72 ( 1.68 )
        30 min
    17.42 ( 1.91 )
    15.93 ( 1.90 )
        45 min
    23.72 ( 2.05 )
    22.60 ( 2.17 )
        1 hour
    31.82 ( 2.02 )
    27.70 ( 2.17 )
        2 hours
    29.14 ( 2.35 )
    26.45 ( 2.4 )
        3 hours
    34.68 ( 2.36 )
    29.96 ( 2.41 )
        4 hours
    41.96 ( 2.14 )
    37.02 ( 2.39 )
        5 hours
    48.51 ( 2.09 )
    39.61 ( 2.34 )
        6 hours
    53.13 ( 2.06 )
    43.33 ( 2.39 )
        8 hours
    57.83 ( 2.09 )
    49.99 ( 2.24 )
        12 hours
    64.98 ( 1.89 )
    55.94 ( 2.16 )
        24 hours
    64.95 ( 1.67 )
    57.29 ( 1.89 )
        48 hours
    81.45 ( 1.30 )
    76.74 ( 1.57 )
        72 hours
    90.58 ( 1.33 )
    88.45 ( 1.49 )
        96 hours
    94.91 ( 0.78 )
    92.39 ( 1.12 )
        216 hours
    97.21 ( 0.65 )
    97.85 ( 0.64 )
    Statistical analysis title
    		 ANOVA
    Statistical analysis description
    The number of subjects starting from 2 hours up to 216 hours differs from specified in the selected comparison groups because the evaluation was carried on observed cases.
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [1]
    Method
    		 ANOVA
    Confidence interval
    Notes
    [1] - Significant differences were detected from 5 hours up to 48 hours.

    Secondary: Acceptability (m-ITT)

    		 Close Top of page
    End point title
    		 Acceptability (m-ITT)
    End point description
    Individual acceptability of vaginal pessary comfortable was assessed through the completion of a questionnaire on the following items: sticky, greasy, stain after application, flowing out of the vagina, and easily to dissolve. Results on the use of vaginal pessary are reported while the results on other items are attached.
    End point type
    Secondary
    End point timeframe
    Patient’s acceptability of the drug treatment was assessed through the completion of a questionnaire, administered by the Investigator at Visit 2, or at ETTV.
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    221
    Units: Comfortable
    number (not applicable)
        Comfortable use of the vaginal pessary
    96.8
    91.4
        Uncomfortable use of vaginal pessary
    3.2
    8.6
    Attachments
    		 Untitled (Filename: Acceptability BeTreat Tab.docx)
    No statistical analyses for this end point

    Post-hoc: Time to 50% reduction of total score symptoms (m-ITT)

    		 Close Top of page
    End point title
    		 Time to 50% reduction of total score symptoms (m-ITT)
    End point description
    A post-hoc analysis was carried out to evaluate the clinical response, in terms of the time to first relief of symptoms, defined as the earliest time when the sum of the scores for all symptoms is reduced by 50% or more with respect to the sum of the scores at Screening/Baseline.
    End point type
    Post-hoc
    End point timeframe
    The time to first relief of symptoms was determined after the first IMP administration, using a specific 4-point scale: 0=absent, 1=mild, 2=moderate, 3=severe.
    End point values
    		 Test: BNZ 6 mg / ECONAZOLE 150 mg Reference: ECONAZOLE 150 mg
    Number of subjects analysed
    222
    223
    Units: percent
        number (not applicable)
    99.55
    98.64
    Statistical analysis title
    		 Survival analysis
    Comparison groups
    Test: BNZ 6 mg / ECONAZOLE 150 mg v Reference: ECONAZOLE 150 mg
    Number of subjects included in analysis
    445
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.0003
    Method
    		 Logrank
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    The timeframe for reporting adverse events is from informed Consent signature up to the telephonic follow-up or Follow-up Visit.
    Adverse event reporting additional description
    Separate evaluations were performed on pre-treatment AEs and on Treatment Emergent Adverse Events (TEAEs), if applicable. A TEAE is defined as any event started on or after the first study medication administration date and was not a pre-existing medical condition.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Patients who took BNZ 6 mg_ECONAZOLE 150 mg
    Reporting group description
    		 Patients receiving the Benzydamine HCl 6 mg and Econazole nitrate 150 mg vaginal pessary, 1 pessary (2.7 g) once daily for 3 consecutive days.

    Reporting group title
    Patients who took ECONAZOLE 150 mg
    Reporting group description
    		 Patients receiving ECONAZOLE 150 mg (Pevaryl®) pessary, 1 pessary (2.7 g) once daily for 3 consecutive days.

    Serious adverse events
    		 Patients who took BNZ 6 mg_ECONAZOLE 150 mg Patients who took ECONAZOLE 150 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 222 (0.45%)
    0 / 223 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Gastrointestinal disorders
    Abdominal pain
    Additional description: The event was of moderate intensity and relationship was judged as unlikely. The condition completely recovered after 24 hours.
         subjects affected / exposed
    1 / 222 (0.45%)
    0 / 223 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Patients who took BNZ 6 mg_ECONAZOLE 150 mg Patients who took ECONAZOLE 150 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Vulvovaginal burning sensation
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Investigations
    ALT increased
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    AST increased
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Blood glucose increased
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Blood pressure increased
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    1
    Blood triglycerides increased
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Ligament sprain
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    4
    3
    Somnolence
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Haemorrhoids
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    1
    Oesophageal pain
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    2
    3
    Hepatobiliary disorders
    Cholecystitis chronic
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Hypertonic bladder
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Cystitis
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Influenza
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    3
    0
    Pharyngitis
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    0
    2
    Pulpitis dental
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    2
    0
    Respiratory tract infection viral
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Rhinitis
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0
    Urinary tract infection
         subjects affected / exposed
    25 / 222 (11.26%)
    22 / 223 (9.87%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 May 2017
    The substantial Amendment no. 1 proposed changes addressed some requestes raised by the Italian Competent Authorithy (AIFA) during the review of the documentation submitted for the study approval. The changes regarded mainly inclusion/exclusion criteria and efficacy assessment. Some minor changes were performed to correct typing errors or better details the study procedures already described. This amendment was approved by National Ethics Committee and Competent Authority.
    18 Dec 2017
    The non-substantial Amendment no. 2 proposed an update of the Investigator’s Brochure due to the availability of the final results from two Phase I clinical trials performed with the new combination containing 6 mg Benzydamine HCl and 150 mg Econazole nitrate (both as vaginal cream and pessary). In addition, changes regarding Sponsor Personnel involved in the study and a correction of an inaccuracy were also proposed. This amendments was approved by National Ethics Committee and Competent Authority when applicable.

    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.
    Not applicable
    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-Mon May 06 14:14:01 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA