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    Clinical Trial Results:
    BOTOX® in the Treatment of Urinary Incontinence Due to Overactive Bladder in Patients 12 to 17 Years of Age

    Summary
    EudraCT number
    		 2014-000464-17
    Trial protocol
    		 GB   CZ   BE   IT   NL   NO   PL   FR  
    Global end of trial date
    10 Feb 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    08 Feb 2023
    First version publication date
    20 Aug 2022
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Edit to data table and arm descriptions.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    191622-137
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02097121
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Allergan
    Sponsor organisation address
    2525 Dupont Drive, Irvine, CA, United States, 92612
    Public contact
    Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
    Scientific contact
    Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    10 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Feb 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    This was a multicenter, randomized, double-blind, parallel-group, multiple-dose study to evaluate the efficacy and safety of BOTOX in adolescents with urinary incontinence due to overactive bladder (OAB) with inadequate management with anticholinergic therapy. Subjects were randomized in a 1:1:1 ratio to receive a single Tx of 25 U, 50 U, or 100 U BOTOX (not to exceed 6 U/kg) on Day 1, were seen after each treatment at Wks 2, 6, and 12 post-treatment, and thereafter at alternating telephone and clinic visits every 6 weeks until they qualified for further retreatment/exited the study. Subjects could receive multiple treatments dependent upon the number and timing of patient requests/qualification for retreatment. At each retreatment the investigator could keep the dose the same or increase it one dose level in a blinded fashion. Subjects exited the study once 96 weeks have elapsed since entry on Day 1 and at least 12 weeks follow-up since their last study treatment had occurred.
    Protection of trial subjects
    Written informed consent was to be obtained from each patient and/or from the patient’s legally authorized representative prior to initiating any study-related activities or procedures. If the patient was under the legal age of consent, the consent form must have been signed by the legally authorized representative in accordance with the relevant country and local regulatory requirements. Written parental/legally authorized representative informed consent in addition to a separate written minor consent and/or assent (in accordance with any applicable state and local laws/regulations) was required for each minor study patient prior to study enrollment or any study-related procedures in the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 May 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
    Poland: 4
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Canada: 11
    Country: Number of subjects enrolled
    United States: 4
    Country: Number of subjects enrolled
    Czechia: 2
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    United Kingdom: 21
    Worldwide total number of subjects
    56
    EEA total number of subjects
    17
    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)
    56
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study included a 28-day screening period.

    Period 1
    Period 1 title
    Overall Study
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Botox 25 U
    Arm description
    		 Participants randomized to receive 25 Units (U) BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone. Posttreatment follow-up clinic visits occurred at Weeks 2, 6, and 12. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BOTOX®
    Investigational medicinal product code
    9060X
    Other name
    Botulinum Toxin Type A
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.

    Arm title
    		 Botox 50 U
    Arm description
    		 Participants randomized to receive 50 Units (U) BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone. Posttreatment follow-up clinic visits occurred at Weeks 2, 6, and 12. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BOTOX®
    Investigational medicinal product code
    9060X
    Other name
    Botulinum Toxin Type A
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.

    Arm title
    		 Botox 100 U
    Arm description
    		 Participants randomized to receive 100 Units (U) BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone. Posttreatment follow-up clinic visits occurred at Weeks 2, 6, and 12. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BOTOX®
    Investigational medicinal product code
    9060X
    Other name
    Botulinum Toxin Type A
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.

    Number of subjects in period 1 [1]
    		Botox 25 U Botox 50 U Botox 100 U
    Started
    19
    18
    19
    Received any treatment
    19
    17
    19
    Actual Treatment Received in Cycle 1
    18
    17
    20
    Actual Treatment Received in Cycle 2
    1 [2]
    17
    28
    Actual Treatment Received in Cycle 3
    2 [3]
    7 [4]
    13
    Actual Treatment Received in Cycle 4
    0 [5]
    1 [6]
    3
    Completed
    12
    12
    9
    Not completed
    7
    6
    19
         Adverse event, non-fatal
    -
    1
    -
         Other, not specified
    4
    2
    3
         Not specified
    -
    -
    9
         Lost to follow-up
    1
    1
    2
         Lack of efficacy
    2
    1
    3
         Withdrawal by subject
    -
    1
    2
    Joined
    0
    0
    9
         Subject assigned to 25 U rcvd 100 U in Cycle 2
    -
    -
    1
         Transferred in from other group/arm
    -
    -
    7
         Subject assigned to 25 U rcvd 100 U in Cycle 1
    -
    -
    1
    Notes
    [1] - The number of subjects transferring in and out of the arms in the period are not the same. It is expected the net number of transfers in and out of the arms in a period, will be zero.
    Justification: Subjects were randomized in a 1:1:1 ratio to 1 of 3 treatment arms. Randomization was stratified by baseline daytime urinary urgency incontinence episodes (a total of ≤6 episodes or > 6 episodes over the 2-day bladder diary collection period). Subjects could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. Retreatment dose was determined by the Investigator and could be at same dose or at the next higher dose compared with the preceding dose.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: One participant assigned to 25 U BOTOX received 100 U BOTOX in Cycle 1 in error. One participant assigned to 25 U BOTOX received 100 U BOTOX in Cycle 2 in error. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: One participant assigned to 25 U BOTOX received 100 U BOTOX in Cycle 1 in error. One participant assigned to 25 U BOTOX received 100 U BOTOX in Cycle 2 in error. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: One participant assigned to 100 U BOTOX received 50 U BOTOX in Cycle 2 in error. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: One participant assigned to 25 U BOTOX received 100 U BOTOX in Cycle 1 in error. One participant assigned to 25 U BOTOX received 100 U BOTOX in Cycle 2 in error. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: One participant assigned to 100 U BOTOX received 50 U BOTOX in Cycle 2 in error. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.
    Period 2
    Period 2 title
    BOTOX-treated population
    Is this the baseline period?
    		 Yes [7]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 BOTOX 25 U (BOTOX-Treated Population)
    Arm description
    		 Participants received 25 U BOTOX in Treatment Cycle 1
    Arm type
    		 Experimental

    Investigational medicinal product name
    BOTOX®
    Investigational medicinal product code
    9060X
    Other name
    Botulinum Toxin Type A
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.

    Arm title
    		 BOTOX 50 U (BOTOX-Treated Population)
    Arm description
    		 Participants received 50 U BOTOX in Treatment Cycle 1
    Arm type
    		 Experimental

    Investigational medicinal product name
    BOTOX®
    Investigational medicinal product code
    9060X
    Other name
    Botulinum Toxin Type A
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.

    Arm title
    		 BOTOX 100 U (BOTOX-Treated Population)
    Arm description
    		 Participants received 100 U BOTOX in Treatment Cycle 1
    Arm type
    		 Experimental

    Investigational medicinal product name
    BOTOX®
    Investigational medicinal product code
    9060X
    Other name
    Botulinum Toxin Type A
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.

    Notes
    [7] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: The BOTOX-treated population (all participants enrolled into the study who received at least 1 BOTOX treatment) is presented according to the dose received in the first treatment cycle
    Number of subjects in period 2 [8] [9]
    		BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Started
    12
    12
    9
    Completed
    18
    17
    20
    Joined
    6
    5
    11
         BOTOX-treated subjects
    6
    5
    10
         Transferred in from other group/arm
    -
    -
    1
    Notes
    [8] - 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: The BOTOX-treated population (all participants enrolled into the study who received at least 1 BOTOX treatment) is presented according to the dose received in the first treatment cycle
    [9] - The number of subjects transferring in and out of the arms in the period are not the same. It is expected the net number of transfers in and out of the arms in a period, will be zero.
    Justification: The BOTOX-treated population (all participants enrolled into the study who received at least 1 BOTOX treatment) is presented according to the dose received in the first treatment cycle.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    BOTOX 25 U (BOTOX-Treated Population)
    Reporting group description
    		 Participants received 25 U BOTOX in Treatment Cycle 1

    Reporting group title
    BOTOX 50 U (BOTOX-Treated Population)
    Reporting group description
    		 Participants received 50 U BOTOX in Treatment Cycle 1

    Reporting group title
    BOTOX 100 U (BOTOX-Treated Population)
    Reporting group description
    		 Participants received 100 U BOTOX in Treatment Cycle 1

    Reporting group values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population) Total
    Number of subjects
    		 18 17 20 55
    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)
    		 18 17 20 55
        Adults (18-64 years)
    		 0 0 0 0
        From 65-84 years
    		 0 0 0 0
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 13.7 ± 1.49 14.3 ± 1.86 14.0 ± 1.75 -
    Gender categorical
    Units: Subjects
        Female
    		 16 17 14 47
        Male
    		 2 0 6 8
    Race
    Units: Subjects
        White
    		 12 12 17 41
        Black or African American
    		 0 0 0 0
        Asian
    		 0 1 0 1
        Hispanic
    		 0 0 0 0
        Other
    		 1 1 1 3
        Not Reported
    		 2 1 1 4
        Unknown
    		 3 2 1 6
    Daily Frequency of Daytime Urinary Incontinence Episodes
    A bladder diary was used to log each daytime urgency episode over 2 consecutive days during screening.
    Units: number of episodes
        arithmetic mean (standard deviation)
    		 5.29 ± 3.447 3.54 ± 2.696 3.64 ± 2.951 -

    End points

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    End points reporting groups
    Reporting group title
    Botox 25 U
    Reporting group description
    		 Participants randomized to receive 25 Units (U) BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone. Posttreatment follow-up clinic visits occurred at Weeks 2, 6, and 12. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.

    Reporting group title
    Botox 50 U
    Reporting group description
    		 Participants randomized to receive 50 Units (U) BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone. Posttreatment follow-up clinic visits occurred at Weeks 2, 6, and 12. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.

    Reporting group title
    Botox 100 U
    Reporting group description
    		 Participants randomized to receive 100 Units (U) BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone. Posttreatment follow-up clinic visits occurred at Weeks 2, 6, and 12. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment.
    Reporting group title
    BOTOX 25 U (BOTOX-Treated Population)
    Reporting group description
    		 Participants received 25 U BOTOX in Treatment Cycle 1

    Reporting group title
    BOTOX 50 U (BOTOX-Treated Population)
    Reporting group description
    		 Participants received 50 U BOTOX in Treatment Cycle 1

    Reporting group title
    BOTOX 100 U (BOTOX-Treated Population)
    Reporting group description
    		 Participants received 100 U BOTOX in Treatment Cycle 1

    Subject analysis set title
    BOTOX 25 U (BOTOX-Treated Population)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received 25 U BOTOX in a given Treatment Cycle

    Subject analysis set title
    BOTOX 50 U (BOTOX-Treated Population)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received 50 U BOTOX in a given Treatment Cycle

    Subject analysis set title
    BOTOX 100 U (BOTOX-Treated Population)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received 100 U BOTOX in a given Treatment Cycle

    Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1

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    End point title
    		 Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1
    End point description
    Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
    End point type
    Primary
    End point timeframe
    From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [1]
    17 [2]
    20 [3]
    Units: urinary incontinence episodes per day
        least squares mean (standard error)
    -1.37 ± 0.801
    -0.97 ± 0.811
    -2.35 ± 0.746
    Notes
    [1] - Subjects with analysis values at both baseline and Week 12
    [2] - Subjects with analysis values at both baseline and Week 12
    [3] - Subjects with analysis values at both baseline and Week 12
    Statistical analysis title
    		 Treatment Difference of 100 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group as factor. A hierarchical analysis strategy to adjust for multiplicity was used.
    Comparison groups
    BOTOX 25 U (BOTOX-Treated Population) v BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3802
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.203
         upper limit
    		 1.243
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.107
    Statistical analysis title
    		 Treatment Difference of 50 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group as factor. A hierarchical analysis strategy to adjust for multiplicity was used.
    Comparison groups
    BOTOX 25 U (BOTOX-Treated Population) v BOTOX 50 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.733
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.921
         upper limit
    		 2.712
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.154

    Secondary: Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Micturition Episodes

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    End point title
    		 Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Micturition Episodes
    End point description
    Micturition was defined as toilet voids recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime micturition episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
    End point type
    Secondary
    End point timeframe
    From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [4]
    17 [5]
    20 [6]
    Units: micturition episodes per day
        least squares mean (standard error)
    -1.84 ± 1.027
    0.31 ± 1.014
    -1.02 ± 0.983
    Notes
    [4] - Subjects with analysis values at both baseline and Week 12
    [5] - Subjects with analysis values at both baseline and Week 12
    [6] - Subjects with analysis values at both baseline and Week 12
    Statistical analysis title
    		 Treatment Difference of 100 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 100 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5743
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.082
         upper limit
    		 3.713
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.442
    Statistical analysis title
    		 Treatment Difference of 50 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 50 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1451
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.769
         upper limit
    		 5.078
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.455

    Secondary: Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Urgency Episodes

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    End point title
    		 Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Urgency Episodes
    End point description
    Participants recorded daytime urgency episodes in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime urgency episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
    End point type
    Secondary
    End point timeframe
    From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [7]
    17 [8]
    20 [9]
    Units: urgency episodes per day
        least squares mean (standard error)
    -1.85 ± 1.014
    -1.78 ± 0.998
    -2.18 ± 0.945
    Notes
    [7] - Subjects with analysis values at both baseline and Week 12
    [8] - Subjects with analysis values at both baseline and Week 12
    [9] - Subjects with analysis values at both baseline and Week 12
    Statistical analysis title
    		 Treatment Difference of 100 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 100 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8206
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.205
         upper limit
    		 2.551
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.434
    Statistical analysis title
    		 Treatment Difference of 50 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 25 U (BOTOX-Treated Population) v BOTOX 50 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9604
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.807
         upper limit
    		 2.95
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.434

    Secondary: Percentage of Participants With Night Time Urinary Incontinence

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    End point title
    		 Percentage of Participants With Night Time Urinary Incontinence
    End point description
    Urinary incontinence was defined as involuntary loss of urine. Participants recorded night time urinary incontinence episodes in a bladder diary during 2 consecutive days in the week prior to the study visit. Night time is defined as the time between going to bed to sleep for the night and waking up to start the next day. The number of daily night time urinary incontinence episodes were averaged during the 2-day period. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
    End point type
    Secondary
    End point timeframe
    From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [10]
    17 [11]
    20 [12]
    Units: percentage of partipants
    number (not applicable)
        Baseline—0 nights
    22.2
    52.9
    35.0
        Baseline—1 night
    27.8
    11.8
    15.0
        Baseline—2 nights
    50.0
    35.3
    50.0
        Week 12—0 nights
    50.0
    76.5
    50.0
        Week 12—1 night
    22.2
    5.9
    15.0
        Week 12—2 nights
    27.8
    17.6
    35.0
    Notes
    [10] - Subjects with analysis values at both baseline and Week 12
    [11] - Subjects with analysis values at both baseline and Week 12
    [12] - Subjects with analysis values at both baseline and Week 12
    No statistical analyses for this end point

    Secondary: Change From Study Baseline in the Daily Average Volume Voided Per Micturition (mL)

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    End point title
    		 Change From Study Baseline in the Daily Average Volume Voided Per Micturition (mL)
    End point description
    The volume per micturition was derived from the total urine volume voided over 1 daytime period during the 2-day bladder diary collection period divided by the number of voids in the same daytime period. Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
    End point type
    Secondary
    End point timeframe
    From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [13]
    17 [14]
    20 [15]
    Units: mL
        least squares mean (standard error)
    -9.17 ± 15.924
    24.94 ± 17.047
    26.16 ± 15.900
    Notes
    [13] - Subjects with analysis values at both baseline and Week 12
    [14] - Subjects with analysis values at both baseline and Week 12
    [15] - Subjects with analysis values at both baseline and Week 12
    Statistical analysis title
    		 Treatment Difference of 100 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 100 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1174
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    35.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.207
         upper limit
    		 79.873
    Variability estimate
    Standard error of the mean
    Dispersion value
    22.175
    Statistical analysis title
    		 Treatment Difference of 50 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 50 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1567
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    34.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.536
         upper limit
    		 81.76
    Variability estimate
    Standard error of the mean
    Dispersion value
    23.722

    Secondary: Change From Study Baseline in Pediatric Urinary Incontinence Quality of Life Total Score (PinQ)

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    End point title
    		 Change From Study Baseline in Pediatric Urinary Incontinence Quality of Life Total Score (PinQ)
    End point description
    The PinQ is a 20-item questionnaire that asks about the subject’s incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time) and a total sum score is calculated (from 0 to 80), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement.
    End point type
    Secondary
    End point timeframe
    From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [16]
    17 [17]
    20 [18]
    Units: units on a scale
        least squares mean (standard error)
    -6.96 ± 2.841
    -5.11 ± 3.243
    -8.28 ± 2.979
    Notes
    [16] - Subjects with analysis values at both baseline and Week 12
    [17] - Subjects with analysis values at both baseline and Week 12
    [18] - Subjects with analysis values at both baseline and Week 12
    Statistical analysis title
    		 Treatment Difference of 100 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 100 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7481
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.553
         upper limit
    		 6.909
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.091
    Statistical analysis title
    		 Treatment Difference of 50 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 25 U (BOTOX-Treated Population) v BOTOX 50 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6691
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.799
         upper limit
    		 10.498
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.299

    Secondary: Change From Study Baseline in PinQ item ‘I am worried that people might think my clothes smell like pee”

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    End point title
    		 Change From Study Baseline in PinQ item ‘I am worried that people might think my clothes smell like pee”
    End point description
    The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the subject’s incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement.
    End point type
    Secondary
    End point timeframe
    From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [19]
    17 [20]
    20 [21]
    Units: units on a scale
        least squares mean (standard error)
    -0.06 ± 0.238
    -0.37 ± 0.273
    -0.09 ± 0.251
    Notes
    [19] - Subjects with analysis values at both baseline and Week 12
    [20] - Subjects with analysis values at both baseline and Week 12
    [21] - Subjects with analysis values at both baseline and Week 12
    Statistical analysis title
    		 Treatment Difference of 100 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 100 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9297
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.721
         upper limit
    		 0.661
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.343
    Statistical analysis title
    		 Treatment Difference of 50 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 25 U (BOTOX-Treated Population) v BOTOX 50 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3976
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.022
         upper limit
    		 0.413
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.357

    Secondary: Change From Study Baseline in PinQ item ‘My bladder problem makes me feel bad about myself”

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    End point title
    		 Change From Study Baseline in PinQ item ‘My bladder problem makes me feel bad about myself”
    End point description
    The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the subject’s incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement.
    End point type
    Secondary
    End point timeframe
    From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [22]
    17 [23]
    20 [24]
    Units: units on a scale
        least squares mean (standard error)
    -0.54 ± 0.209
    -0.15 ± 0.238
    -0.24 ± 0.220
    Notes
    [22] - Subjects with analysis values at both baseline and Week 12
    [23] - Subjects with analysis values at both baseline and Week 12
    [24] - Subjects with analysis values at both baseline and Week 12
    Statistical analysis title
    		 Treatment Difference of 100 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 100 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3309
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.311
         upper limit
    		 0.904
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.302
    Statistical analysis title
    		 Treatment Difference of 50 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 25 U (BOTOX-Treated Population) v BOTOX 50 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2235
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.245
         upper limit
    		 1.024
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.315

    Secondary: Change From Study Baseline in PinQ item ‘I miss out on being with friends because of my bladder problems”

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    End point title
    		 Change From Study Baseline in PinQ item ‘I miss out on being with friends because of my bladder problems”
    End point description
    The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the subject’s incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement.
    End point type
    Secondary
    End point timeframe
    From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [25]
    17 [26]
    20 [27]
    Units: units on a scale
        least squares mean (standard error)
    -0.39 ± 0.193
    -0.24 ± 0.218
    -0.27 ± 0.201
    Notes
    [25] - Subjects with analysis values at both baseline and Week 12
    [26] - Subjects with analysis values at both baseline and Week 12
    [27] - Subjects with analysis values at both baseline and Week 12
    Statistical analysis title
    		 Treatment Difference of 100 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 100 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6689
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.434
         upper limit
    		 0.67
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.274
    Statistical analysis title
    		 Treatment Difference of 50 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes [a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.
    Comparison groups
    BOTOX 25 U (BOTOX-Treated Population) v BOTOX 50 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6076
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.431
         upper limit
    		 0.729
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.288

    Secondary: Percentage of Participants with a Positive Treatment Response in the Modified Treatment Benefit Scale

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    End point title
    		 Percentage of Participants with a Positive Treatment Response in the Modified Treatment Benefit Scale
    End point description
    The Modified Treatment Benefit Scale (Modified TBS) is a single-item scale designed to assess the change in the subject’s overactive bladder (OAB) condition following treatment. The subject’s current condition (urinary problems, urinary incontinence) is compared to their condition prior to receipt of any study treatment by selection of “greatly improved”, “improved”, “not changed” or “worsened”. Subjects who selected “greatly improved” or “improved” were considered to have a positive treatment response.
    End point type
    Secondary
    End point timeframe
    At Week 12 in Treatment Cycle 1
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    17 [28]
    17 [29]
    19 [30]
    Units: percentage of participants
        number (confidence interval 95%)
    52.9 (27.81 to 77.02)
    70.6 (44.04 to 89.69)
    68.4 (43.45 to 87.42)
    Notes
    [28] - Subjects with non-missing values at Week 12.
    [29] - Subjects with non-missing values at Week 12.
    [30] - Subjects with non-missing values at Week 12.
    Statistical analysis title
    		 Treatment Difference of 100 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using the Cochran-Mantel-Haenszel (CMH) method stratified by baseline daytime urinary urgency incontinence episodes (a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period).
    Comparison groups
    BOTOX 100 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6092
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference %
    Point estimate
    15.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.94
         upper limit
    		 46.19
    Statistical analysis title
    		 Treatment Difference of 50 U versus 25 U
    Statistical analysis description
    Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using the Cochran-Mantel-Haenszel (CMH) method stratified by baseline daytime urinary urgency incontinence episodes (a total of ≤ 6 episodes or > 6 episodes over the 2-day diary collection period).
    Comparison groups
    BOTOX 50 U (BOTOX-Treated Population) v BOTOX 25 U (BOTOX-Treated Population)
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4824
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference %
    Point estimate
    17.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.2
         upper limit
    		 48.9

    Secondary: Time to Subject’s First Request for Retreatment

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    End point title
    		 Time to Subject’s First Request for Retreatment
    End point description
    The time from the day of BOTOX treatment to the request for the subsequent treatment was estimated using a Kaplan-Meier survival method for each treatment group. Subjects who did not request retreatment were treated as censored at the time of their last study visit or study exit.
    End point type
    Secondary
    End point timeframe
    From the day of BOTOX treatment in Treatment Cycle 1 to the request for subsequent treatment
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    17 [31]
    14 [32]
    17 [33]
    Units: weeks
        median (confidence interval 95%)
    16.6 (12.71 to 25.29)
    17.6 (11.29 to 38.57)
    21.3 (12.86 to 30.14)
    Notes
    [31] - BOTOX-treated subjects who requested retreatment
    [32] - BOTOX-treated subjects who requested retreatment
    [33] - BOTOX-treated subjects who requested retreatment
    No statistical analyses for this end point

    Secondary: Time to Subject’s Qualification for Retreatment

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    End point title
    		 Time to Subject’s Qualification for Retreatment
    End point description
    The time from the day of BOTOX treatment to the qualification for retreatment was estimated using a Kaplan-Meier survival method for each treatment group. Subjects who did not qualify for retreatment were treated as censored at the time of their last study visit or study exit.
    End point type
    Secondary
    End point timeframe
    From the day of BOTOX treatment in Treatment Cycle 1 to the qualification for retreatment
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    16 [34]
    14 [35]
    17 [36]
    Units: weeks
        median (confidence interval 95%)
    22.5 (13.57 to 36.29)
    18.1 (12.29 to 52.57)
    24.1 (12.86 to 41.57)
    Notes
    [34] - BOTOX-treated subjects who qualified for retreatment
    [35] - BOTOX-treated subjects who qualified for retreatment
    [36] - BOTOX-treated subjects who qualified for retreatment
    No statistical analyses for this end point

    Other pre-specified: Number of Participants With Treatment Emergent Adverse Events

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    End point title
    		 Number of Participants With Treatment Emergent Adverse Events
    End point description
    An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
    End point type
    Other pre-specified
    End point timeframe
    From the first dose of study drug until the last dose, up to 147 weeks
    End point values
    		 BOTOX 25 U (BOTOX-Treated Population) BOTOX 50 U (BOTOX-Treated Population) BOTOX 100 U (BOTOX-Treated Population)
    Number of subjects analysed
    18 [37]
    17 [38]
    28 [39]
    Units: number of participants
        Cycle 1 (n=18, 17, 20)
    13
    12
    14
        Cycle 2 (n=1, 17, 28)
    1
    13
    18
        Cycle 3 (n=2, 7, 13)
    1
    3
    8
        Cycle 4 (n=0, 1, 3)
    0
    1
    1
    Notes
    [37] - All participants enrolled into the study who received at least 1 BOTOX treatment
    [38] - All participants enrolled into the study who received at least 1 BOTOX treatment
    [39] - All participants enrolled into the study who received at least 1 BOTOX treatment
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality is reported from enrollment to the end of study; median time on follow-up was up to 724 days. TEAEs/SAEs were collected from the first dose of study drug until the last dose, up to 147 weeks.
    Adverse event reporting additional description
    For safety analyses, participants were assigned to a treatment group based on the treatment actually received, regardless of the treatment randomized.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    25 U BOTOX All
    Reporting group description
    		 All participants who received 25 U BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    50 U BOTOX All
    Reporting group description
    		 All participants who received 50 U BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    50 U BOTOX Cycle 1
    Reporting group description
    		 Participants who received 50 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 1, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    100 U BOTOX All
    Reporting group description
    		 All participants who received 100 U BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    25 U BOTOX Cycle 1
    Reporting group description
    		 Participants who received 25 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 1, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    100 U BOTOX Cycle 1
    Reporting group description
    		 Participants who received 100 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 1, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    All BOTOX Cycle 1
    Reporting group description
    		 All BOTOX-treated participants in Treatment Cycle 1

    Reporting group title
    25 U BOTOX Cycle 2
    Reporting group description
    		 Participants who received 25 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 2, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    50 U BOTOX Cycle 2
    Reporting group description
    		 Participants who received 50 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 2, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    All BOTOX Cycle 2
    Reporting group description
    		 All BOTOX-treated participants in Treatment Cycle 2

    Reporting group title
    100 U BOTOX Cycle 2
    Reporting group description
    		 Participants who received 100 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 2, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    25 U BOTOX Cycle 3
    Reporting group description
    		 Participants who received 25 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 3, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    50 U BOTOX Cycle 3
    Reporting group description
    		 Participants who received 50 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 3, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    100 U BOTOX Cycle 3
    Reporting group description
    		 Participants who received 100 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 3, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    All BOTOX Cycle 3
    Reporting group description
    		 All BOTOX-treated participants in Treatment Cycle 3

    Reporting group title
    50 U BOTOX Cycle 4
    Reporting group description
    		 Participants who received 50 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 4, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone

    Reporting group title
    100 U BOTOX Cycle 4
    Reporting group description
    		 Participants who received 100 U BOTOX (not to exceed 6 U/kg) in Treatment Cycle 4, administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone.

    Reporting group title
    All BOTOX Cycle 4
    Reporting group description
    		 All BOTOX-treated participants in Treatment Cycle 4

    Serious adverse events
    		 25 U BOTOX All 50 U BOTOX All 50 U BOTOX Cycle 1 100 U BOTOX All 25 U BOTOX Cycle 1 100 U BOTOX Cycle 1 All BOTOX Cycle 1 25 U BOTOX Cycle 2 50 U BOTOX Cycle 2 All BOTOX Cycle 2 100 U BOTOX Cycle 2 25 U BOTOX Cycle 3 50 U BOTOX Cycle 3 100 U BOTOX Cycle 3 All BOTOX Cycle 3 50 U BOTOX Cycle 4 100 U BOTOX Cycle 4 All BOTOX Cycle 4
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    1 / 46 (2.17%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    PALLOR
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    MALAISE
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    SOCIAL PROBLEM
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    ANXIETY DISORDER
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    1 / 46 (2.17%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 25 U BOTOX All 50 U BOTOX All 50 U BOTOX Cycle 1 100 U BOTOX All 25 U BOTOX Cycle 1 100 U BOTOX Cycle 1 All BOTOX Cycle 1 25 U BOTOX Cycle 2 50 U BOTOX Cycle 2 All BOTOX Cycle 2 100 U BOTOX Cycle 2 25 U BOTOX Cycle 3 50 U BOTOX Cycle 3 100 U BOTOX Cycle 3 All BOTOX Cycle 3 50 U BOTOX Cycle 4 100 U BOTOX Cycle 4 All BOTOX Cycle 4
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 18 (66.67%)
    23 / 29 (79.31%)
    12 / 17 (70.59%)
    24 / 33 (72.73%)
    12 / 18 (66.67%)
    14 / 20 (70.00%)
    38 / 55 (69.09%)
    1 / 1 (100.00%)
    13 / 17 (76.47%)
    32 / 46 (69.57%)
    18 / 28 (64.29%)
    1 / 2 (50.00%)
    3 / 7 (42.86%)
    8 / 13 (61.54%)
    12 / 22 (54.55%)
    1 / 1 (100.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    Vascular disorders
    FLUSHING
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    HAEMATOMA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    RAYNAUD'S PHENOMENON
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    CHRONIC FATIGUE SYNDROME
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    1 / 1 (100.00%)
    0 / 17 (0.00%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    FATIGUE
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    ILLNESS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    MALAISE
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    PERIPHERAL SWELLING
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    PYREXIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    2 / 46 (4.35%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    1
    0
    1
    2
    1
    0
    0
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    DYSMENORRHOEA
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    2 / 33 (6.06%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    2 / 46 (4.35%)
    2 / 28 (7.14%)
    0 / 2 (0.00%)
    1 / 7 (14.29%)
    1 / 13 (7.69%)
    2 / 22 (9.09%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    1
    0
    0
    2
    2
    0
    2
    1
    3
    0
    0
    0
    GENITAL PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    HAEMORRHAGIC OVARIAN CYST
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    2 / 46 (4.35%)
    2 / 28 (7.14%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    2
    0
    0
    0
    0
    0
    0
    0
    HEAVY MENSTRUAL BLEEDING
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    1 / 7 (14.29%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    OEDEMA GENITAL
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    VAGINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    VULVOVAGINAL DISCOMFORT
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    2 / 33 (6.06%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    1 / 46 (2.17%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    1
    1
    0
    0
    1
    1
    0
    0
    0
    NASAL CONGESTION
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    2 / 33 (6.06%)
    1 / 18 (5.56%)
    2 / 20 (10.00%)
    4 / 55 (7.27%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    3
    3
    2
    1
    2
    6
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    Psychiatric disorders
    ANOREXIA NERVOSA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    ANXIETY
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Investigations
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    BLOOD URINE PRESENT
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    CRYSTAL URINE PRESENT
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    CYTOMEGALOVIRUS TEST POSITIVE
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    EPSTEIN-BARR VIRUS TEST POSITIVE
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    RED BLOOD CELLS URINE POSITIVE
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    RESIDUAL URINE VOLUME
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    URINE LEUKOCYTE ESTERASE POSITIVE
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Injury, poisoning and procedural complications
    ANIMAL BITE
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    ANIMAL SCRATCH
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    CLAVICLE FRACTURE
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    CONTUSION
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    1 / 7 (14.29%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    FALL
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    1
    0
    0
    2
    0
    2
    0
    1
    1
    0
    0
    0
    1
    1
    0
    0
    0
    JOINT INJURY
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    2 / 33 (6.06%)
    0 / 18 (0.00%)
    2 / 20 (10.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    LIGAMENT SPRAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    1 / 7 (14.29%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    1
    0
    1
    0
    2
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    POST PROCEDURAL DISCOMFORT
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    POST PROCEDURAL HAEMORRHAGE
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    PROCEDURAL PAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    1 / 46 (2.17%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    TENDON INJURY
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    TACHYCARDIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 29 (6.90%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    1 / 2 (50.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    1
    0
    1
    1
    0
    2
    0
    0
    2
    0
    0
    0
    HEADACHE
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 29 (6.90%)
    2 / 17 (11.76%)
    4 / 33 (12.12%)
    0 / 18 (0.00%)
    3 / 20 (15.00%)
    5 / 55 (9.09%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    3 / 46 (6.52%)
    3 / 28 (10.71%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    3 / 13 (23.08%)
    3 / 22 (13.64%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    2
    4
    0
    3
    5
    0
    0
    4
    4
    0
    0
    4
    4
    0
    0
    0
    MIGRAINE
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    1 / 2 (50.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    Ear and labyrinth disorders
    HYPERACUSIS
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    MISOPHONIA
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Eye disorders
    EYE PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    OCULAR HYPERAEMIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    ABDOMINAL PAIN
         subjects affected / exposed
    2 / 18 (11.11%)
    2 / 29 (6.90%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    3 / 55 (5.45%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    3 / 46 (6.52%)
    2 / 28 (7.14%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    1
    0
    2
    0
    3
    0
    1
    3
    2
    0
    0
    0
    0
    0
    0
    0
    ABDOMINAL PAIN LOWER
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    CONSTIPATION
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    1 / 2 (50.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    DIARRHOEA
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    1
    1
    1
    2
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    DYSPEPSIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    IRRITABLE BOWEL SYNDROME
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    NAUSEA
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    2 / 46 (4.35%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    1
    1
    1
    2
    0
    1
    2
    1
    0
    0
    0
    0
    0
    0
    0
    TOOTHACHE
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    2 / 46 (4.35%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    2
    1
    0
    0
    0
    0
    0
    0
    0
    VOMITING
         subjects affected / exposed
    0 / 18 (0.00%)
    3 / 29 (10.34%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    3 / 17 (17.65%)
    3 / 46 (6.52%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    0
    3
    3
    0
    0
    0
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    ACNE
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    ALOPECIA
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    DERMATITIS CONTACT
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    ECZEMA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    NAIL BED INFLAMMATION
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    RASH
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    URTICARIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Renal and urinary disorders
    BLADDER DISCOMFORT
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    BLADDER SPASM
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    DYSURIA
         subjects affected / exposed
    2 / 18 (11.11%)
    5 / 29 (17.24%)
    1 / 17 (5.88%)
    3 / 33 (9.09%)
    2 / 18 (11.11%)
    2 / 20 (10.00%)
    5 / 55 (9.09%)
    0 / 1 (0.00%)
    4 / 17 (23.53%)
    6 / 46 (13.04%)
    2 / 28 (7.14%)
    1 / 2 (50.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    5
    1
    3
    2
    2
    5
    0
    4
    6
    2
    1
    0
    0
    1
    0
    0
    0
    HAEMATURIA
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    0
    0
    0
    3
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    LEUKOCYTURIA
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 29 (6.90%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    2 / 46 (4.35%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    3
    1
    0
    1
    0
    2
    0
    2
    3
    1
    0
    0
    0
    0
    0
    0
    0
    POLLAKIURIA
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    1
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    PROTEINURIA
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    URETHRAL PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    2 / 33 (6.06%)
    0 / 18 (0.00%)
    2 / 20 (10.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    URINARY INCONTINENCE
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    2 / 46 (4.35%)
    2 / 28 (7.14%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    2
    2
    0
    0
    0
    0
    0
    0
    0
    BACK PAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    1
    1
    0
    2
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    FLANK PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    JOINT SWELLING
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    MUSCLE SPASMS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    2
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    MYALGIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    1 / 46 (2.17%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    1
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    SACRAL PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    SPONDYLOLISTHESIS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Infections and infestations
    BACTERIURIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    EAR INFECTION
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 29 (6.90%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    2 / 17 (11.76%)
    2 / 46 (4.35%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    1
    0
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    FUNGAL SKIN INFECTION
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    1 / 2 (50.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 29 (6.90%)
    1 / 17 (5.88%)
    2 / 33 (6.06%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    2 / 46 (4.35%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    1
    2
    0
    1
    2
    0
    1
    2
    1
    0
    0
    0
    0
    0
    0
    0
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    INFLUENZA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    2 / 33 (6.06%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    3 / 46 (6.52%)
    3 / 28 (10.71%)
    0 / 2 (0.00%)
    1 / 7 (14.29%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    0
    1
    0
    0
    3
    3
    0
    1
    0
    1
    0
    0
    0
    LARYNGITIS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    NASOPHARYNGITIS
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 29 (6.90%)
    2 / 17 (11.76%)
    6 / 33 (18.18%)
    1 / 18 (5.56%)
    3 / 20 (15.00%)
    6 / 55 (10.91%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    4 / 46 (8.70%)
    4 / 28 (14.29%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    4
    4
    8
    1
    4
    9
    0
    0
    6
    6
    0
    0
    1
    1
    0
    0
    0
    PARONYCHIA
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    PHARYNGITIS
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    1 / 33 (3.03%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    1 / 46 (2.17%)
    1 / 28 (3.57%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    3
    3
    1
    1
    0
    4
    0
    0
    1
    1
    0
    0
    1
    1
    0
    0
    0
    RESPIRATORY TRACT INFECTION VIRAL
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    RHINOVIRUS INFECTION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    SINUSITIS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    TONSILLITIS
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 29 (6.90%)
    2 / 17 (11.76%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    2 / 55 (3.64%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    4
    4
    1
    0
    0
    4
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    TRACHEOBRONCHITIS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    1 / 17 (5.88%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    2 / 46 (4.35%)
    2 / 28 (7.14%)
    0 / 2 (0.00%)
    1 / 7 (14.29%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    1
    0
    0
    2
    2
    0
    1
    0
    1
    0
    0
    0
    URINARY TRACT INFECTION
         subjects affected / exposed
    2 / 18 (11.11%)
    6 / 29 (20.69%)
    2 / 17 (11.76%)
    6 / 33 (18.18%)
    2 / 18 (11.11%)
    2 / 20 (10.00%)
    6 / 55 (10.91%)
    0 / 1 (0.00%)
    4 / 17 (23.53%)
    13 / 46 (28.26%)
    9 / 28 (32.14%)
    0 / 2 (0.00%)
    2 / 7 (28.57%)
    4 / 13 (30.77%)
    6 / 22 (27.27%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    11
    4
    9
    3
    5
    12
    0
    7
    19
    12
    0
    3
    5
    8
    0
    0
    0
    VIRAL INFECTION
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    1 / 7 (14.29%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    VULVOVAGINAL CANDIDIASIS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    ABNORMAL WEIGHT GAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 29 (0.00%)
    0 / 17 (0.00%)
    1 / 33 (3.03%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 55 (1.82%)
    0 / 1 (0.00%)
    0 / 17 (0.00%)
    0 / 46 (0.00%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    VITAMIN D DEFICIENCY
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 29 (3.45%)
    0 / 17 (0.00%)
    0 / 33 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 55 (0.00%)
    0 / 1 (0.00%)
    1 / 17 (5.88%)
    1 / 46 (2.17%)
    0 / 28 (0.00%)
    0 / 2 (0.00%)
    0 / 7 (0.00%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Feb 2014
    Amendment 1 Details were added to clarify primary analysis and final analysis details including unblinding after primary analysis.
    05 Sep 2014
    Amendment 2/Version 3 Exclusion criteria regarding medical conditions that may put patients at increased risk with exposure to BOTOX were inadvertently omitted in the original protocol and Amendment 1, these were added. Details from investigator’s meeting were also added.

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

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

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