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    Clinical Trial Results:
    A Randomized, Open-Label, Multicenter Study With Open-Label Extension of the Pharmacokinetics and Safety of Topiramate Administered as the Oral Liquid and Sprinkle Formulations as an Adjunct to Concurrent Anticonvulsant Therapy in Infants (Aged 1 to 24 Months, Inclusive) With Refractory Partial-Onset Seizures.

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    		 2005-001339-31
    Trial protocol
    		 ES  
    Global end of trial date
    31 Oct 2007

    Results information
    Results version number
    		 v2(current)
    This version publication date
    15 Jul 2016
    First version publication date
    02 Aug 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Review of data

    Trial information

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    Trial identification
    Sponsor protocol code
    TOPMAT-PEP-1002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00233012
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Janssen Research & Development, LLC
    Sponsor organisation address
    Archimedsweg 29-2333CM, Leiden, Netherlands, B235-0
    Public contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.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
    31 Oct 2007
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Oct 2007
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study was to determine the concentration-time profile for topiramate using a sparse sampling scheme following topiramate administration at fixed doses between 3 to 25 milligram per kilogram per day (mg/kg/day), of either oral liquid or sprinkle capsule formulations in infants aged 1 to 24 months, inclusive, with refractory partial-onset seizures (POS) taking at least 1 concomitant antiepileptic drug (AED).
    Protection of trial subjects
    The Safety assessments include type and number of seizures, clinical laboratory results, physical examination, 12-lead electrocardiogram (ECG), vital signs, neurologic examination, vineland scales of adaptive behavior, and renal ultrasound. Adverse events and vital signs were monitored throughout the study. Assessments for adequate food and liquid intake, hyperthermia, oligohydrosis, and rash were also to be performed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Jun 2005
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 1
    Country: Number of subjects enrolled
    India: 6
    Country: Number of subjects enrolled
    Russian Federation: 13
    Country: Number of subjects enrolled
    Ukraine: 17
    Country: Number of subjects enrolled
    United States: 18
    Worldwide total number of subjects
    55
    EEA total number of subjects
    0
    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)
    55
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 61 subjects were screened, among those 55 subjects were received at least 1 dose of study drug and finally 50 Subjects completed the study.

    Period 1
    Period 1 title
    Open Label Treatment
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Topiramate (TPM) 3 mg/kg/day
    Arm description
    		 Participants were administered with Topiramate 3 Milligram per Kilogram (mg/kg) liquid formulation orally twice in a day.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Topiramate
    Investigational medicinal product code
    Other name
    TOPAMAX
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered Topiramate 3 mg (milligram)/kilogram (kg) oral liquid/ oral capsule twice daily for 42 days.

    Arm title
    		 Topiramate (TPM) 5 mg/kg/day
    Arm description
    		 Participants were administered with Topiramate 5 Milligram per Kilogram (mg/kg) oral liquid / oral capsule formulation orally twice in a day.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Topiramate
    Investigational medicinal product code
    Other name
    TOPAMAX
    Pharmaceutical forms
    Capsule, Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered Topiramate 5 mg (milligram)/kilogram (kg) oral liquid/ oral capsule twice daily for 42 days.

    Arm title
    		 Topiramate (TPM) 15 mg/kg/day
    Arm description
    		 Participants were administered with Topiramate 15 Milligram per Kilogram (mg/kg) oral liquid / oral capsule formulation orally twice in a day.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Topiramate
    Investigational medicinal product code
    Other name
    TOPAMAX
    Pharmaceutical forms
    Capsule, Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered Topiramate 15 mg (milligram)/kilogram (kg) oral liquid/ oral capsule twice daily for 42 days.

    Arm title
    		 Topiramate (TPM) 25 mg/kg/day
    Arm description
    		 Participants were administered with Topiramate 25 Milligram per Kilogram (mg/kg) oral liquid/oral capsule formulation orally twice in a day.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Topiramate Sprinkle Capsules
    Investigational medicinal product code
    Other name
    TOPAMAX
    Pharmaceutical forms
    Capsule, Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered Topiramate 25 milligram per kilogram (mg/kg) oral liquid/ oral capsule twice daily for 42 days.

    Number of subjects in period 1
    		Topiramate (TPM) 3 mg/kg/day Topiramate (TPM) 5 mg/kg/day Topiramate (TPM) 15 mg/kg/day Topiramate (TPM) 25 mg/kg/day
    Started
    14
    13
    13
    15
    Completed
    14
    12
    11
    13
    Not completed
    0
    1
    2
    2
         Consent withdrawn by subject
    -
    -
    -
    1
         Adverse event, non-fatal
    -
    1
    -
    -
         Adverse event
    -
    -
    2
    -
         Lost to follow-up
    -
    -
    -
    1
    Period 2
    Period 2 title
    Open Label Extension
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Topiramate (TPM) upto 60 mg/kg/day
    Arm description
    		 Subjects entering the open-label extension phase at dosages less than 25 mg/kg per day were titrated to this dosage or maximum dosages tolerated over 4 weeks. Subsequently, subjects were titrated up or down depending on tolerability and seizure frequency up to 60 mg/kg per day maximum final dosage
    Arm type
    		 Experimental

    Investigational medicinal product name
    Topiramate
    Investigational medicinal product code
    Other name
    TOPAMAX
    Pharmaceutical forms
    Capsule, Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects who entered the open-label extension phase at dosages less than 25 mg/kg per day were titrated to this dosage or maximum dosages tolerated over 4 weeks. Subsequently, subjects were titrated up or down depending on tolerability and seizure frequency up to 60 mg/kg per day maximum final dosage

    Number of subjects in period 2
    		Topiramate (TPM) upto 60 mg/kg/day
    Started
    50
    Completed
    16
    Not completed
    34
         Withdrawn due to early termination by sponsor
    20
         Adverse event, non-fatal
    6
         Other
    3
         Subject choice (parent withdrew consent)
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Topiramate (TPM) 3 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 3 Milligram per Kilogram (mg/kg) liquid formulation orally twice in a day.

    Reporting group title
    Topiramate (TPM) 5 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 5 Milligram per Kilogram (mg/kg) oral liquid / oral capsule formulation orally twice in a day.

    Reporting group title
    Topiramate (TPM) 15 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 15 Milligram per Kilogram (mg/kg) oral liquid / oral capsule formulation orally twice in a day.

    Reporting group title
    Topiramate (TPM) 25 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 25 Milligram per Kilogram (mg/kg) oral liquid/oral capsule formulation orally twice in a day.

    Reporting group values
    		 Topiramate (TPM) 3 mg/kg/day Topiramate (TPM) 5 mg/kg/day Topiramate (TPM) 15 mg/kg/day Topiramate (TPM) 25 mg/kg/day Total
    Number of subjects
    		 14 13 13 15 55
    Title for AgeCategorical
    Units: subjects
        infants and toddlers(28 days-23 months)
    		 14 13 13 15 55
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 0 0 0 0 0
        From 65 to 84 years
    		 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0
    Title for AgeContinuous
    Units: Months
        arithmetic mean (standard deviation)
    		 10.9 ( 5.38 ) 12 ( 5.46 ) 11.6 ( 6.74 ) 11.3 ( 6.11 ) -
    Title for Gender
    Units: subjects
        Female
    		 8 3 7 5 23
        Male
    		 6 10 6 10 32

    End points

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    End points reporting groups
    Reporting group title
    Topiramate (TPM) 3 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 3 Milligram per Kilogram (mg/kg) liquid formulation orally twice in a day.

    Reporting group title
    Topiramate (TPM) 5 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 5 Milligram per Kilogram (mg/kg) oral liquid / oral capsule formulation orally twice in a day.

    Reporting group title
    Topiramate (TPM) 15 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 15 Milligram per Kilogram (mg/kg) oral liquid / oral capsule formulation orally twice in a day.

    Reporting group title
    Topiramate (TPM) 25 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 25 Milligram per Kilogram (mg/kg) oral liquid/oral capsule formulation orally twice in a day.
    Reporting group title
    Topiramate (TPM) upto 60 mg/kg/day
    Reporting group description
    		 Subjects entering the open-label extension phase at dosages less than 25 mg/kg per day were titrated to this dosage or maximum dosages tolerated over 4 weeks. Subsequently, subjects were titrated up or down depending on tolerability and seizure frequency up to 60 mg/kg per day maximum final dosage

    Primary: Serum Trough Concentration (C-trough) of Topiramate

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    End point title
    		 Serum Trough Concentration (C-trough) of Topiramate [1]
    End point description
    The C-trough is the observed serum concentration immediately prior to the next administration of topiramate.
    End point type
    Primary
    End point timeframe
    Predose, within the intervals of 1 to 3, 4 to 6, and 8 to 10 hours postdose on Day 7
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed for this endpoint.
    End point values
    		 Topiramate (TPM) 3 mg/kg/day Topiramate (TPM) 5 mg/kg/day Topiramate (TPM) 15 mg/kg/day Topiramate (TPM) 25 mg/kg/day
    Number of subjects analysed
    9
    9
    8
    9
    Units: microgram per millilitre (μg/mL)
        arithmetic mean (standard deviation)
    1.91 ( 1.04 )
    3.25 ( 1.89 )
    9.74 ( 4.82 )
    13.6 ( 5.19 )
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours

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    End point title
    		 Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours [2]
    End point description
    The AUC(0-12) is defined as Area under the plasma concentration-time curve from time 0 through 12 hours post dosing.
    End point type
    Primary
    End point timeframe
    Predose, within the intervals of 1 to 3, 4 to 6, and 8 to 10 hours postdose on Day 7
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed for this endpoint.
    End point values
    		 Topiramate (TPM) 3 mg/kg/day Topiramate (TPM) 5 mg/kg/day Topiramate (TPM) 15 mg/kg/day Topiramate (TPM) 25 mg/kg/day
    Number of subjects analysed
    9
    9
    8
    9
    Units: microgram*hour per millilitre (μg.h/mL)
        arithmetic mean (standard deviation)
    29.1 ( 12.4 )
    50 ( 19.6 )
    143 ( 53.8 )
    211 ( 58 )
    No statistical analyses for this end point

    Primary: Creatinine Clearance (CLCR) of Topiramate

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    End point title
    		 Creatinine Clearance (CLCR) of Topiramate [3]
    End point description
    The CLCR is defined as the volume of serum or plasma that would be cleared of creatinine by one minute's excretion of urine.
    End point type
    Primary
    End point timeframe
    Up to Day 42
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed for this endpoint.
    End point values
    		 Topiramate (TPM) 3 mg/kg/day Topiramate (TPM) 5 mg/kg/day Topiramate (TPM) 15 mg/kg/day Topiramate (TPM) 25 mg/kg/day
    Number of subjects analysed
    9
    9
    8
    9
    Units: millilitre per minute per 1.73 meter^3
        arithmetic mean (standard deviation)
    111 ( 37.2 )
    102 ( 12.7 )
    87.8 ( 20.8 )
    90.9 ( 17.3 )
    No statistical analyses for this end point

    Primary: Apparent Oral Clearance (CLss/F) of Topiramate

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    End point title
    		 Apparent Oral Clearance (CLss/F) of Topiramate [4]
    End point description
    The CLss/F is defined as total clearance of the drug from plasma after oral administration.
    End point type
    Primary
    End point timeframe
    Up to Day 42
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed for this endpoint.
    End point values
    		 Topiramate (TPM) 3 mg/kg/day Topiramate (TPM) 5 mg/kg/day Topiramate (TPM) 15 mg/kg/day Topiramate (TPM) 25 mg/kg/day
    Number of subjects analysed
    9
    9
    8
    9
    Units: millilitre per minute (mL/min)
        arithmetic mean (standard deviation)
    7.73 ( 3.38 )
    9.04 ( 4.57 )
    9.1 ( 5.08 )
    8.49 ( 2.44 )
    No statistical analyses for this end point

    Primary: Apparent Oral Clearance (CLss/F) of Topiramate

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    End point title
    		 Apparent Oral Clearance (CLss/F) of Topiramate [5]
    End point description
    The CLss/F is defined as total clearance of the drug from plasma after oral administration.
    End point type
    Primary
    End point timeframe
    Up to Day 42
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed for this endpoint.
    End point values
    		 Topiramate (TPM) 3 mg/kg/day Topiramate (TPM) 5 mg/kg/day Topiramate (TPM) 15 mg/kg/day Topiramate (TPM) 25 mg/kg/day
    Number of subjects analysed
    9
    9
    8
    9
    Units: Litre per hour (L/h)
        arithmetic mean (standard deviation)
    0.464 ( 0.203 )
    0.542 ( 0.274 )
    0.546 ( 0.305 )
    0.509 ( 0.147 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Screening up to Follow-up (up to 30 days after prior visit)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 WHOART
    Dictionary version
    SOC3
    Reporting groups
    Reporting group title
    Topiramate (TPM) 3 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 3-Milligram per Kilogram (mg/kg) liquid formulation orally twice in a day.

    Reporting group title
    Topiramate (TPM) 25 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 25-Milligram per Kilogram (mg/kg) oral liquid /oral capsule formulation twice in a day.

    Reporting group title
    Topiramate (TPM) 15 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 15-Milligram per Kilogram (mg/kg) oral liquid/oral capsule formulation twice in a day.

    Reporting group title
    Topiramate (TPM) 5 mg/kg/day
    Reporting group description
    		 Participants were administered with Topiramate 5-Milligram per Kilogram (mg/kg) oral liquid/oral capsule formulation twice in a day.

    Serious adverse events
    		 Topiramate (TPM) 3 mg/kg/day Topiramate (TPM) 25 mg/kg/day Topiramate (TPM) 15 mg/kg/day Topiramate (TPM) 5 mg/kg/day
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 13 (53.85%)
    2 / 10 (20.00%)
    7 / 20 (35.00%)
    5 / 12 (41.67%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Brain Neoplasm Benign
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsions Aggravated
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    2 / 20 (10.00%)
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Convulsions Grand Mal
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Psychomotor Development Impaired
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Splenomegaly
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse Event Nos
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug Level Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fever
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection Viral
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 10 (10.00%)
    3 / 20 (15.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis Media
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastroenteritis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatomegaly
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    3 / 20 (15.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stridor
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper Resp Tract Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Somnolence
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Pyelonephritis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperammonaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Topiramate (TPM) 3 mg/kg/day Topiramate (TPM) 25 mg/kg/day Topiramate (TPM) 15 mg/kg/day Topiramate (TPM) 5 mg/kg/day
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 13 (100.00%)
    10 / 10 (100.00%)
    20 / 20 (100.00%)
    12 / 12 (100.00%)
    Vascular disorders
    Extrasystoles Supraventricular
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vasospasm
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Pregnancy, puerperium and perinatal conditions
    Autism Infantile
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Atrial Septal Defect
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    3
    Congenital Anomaly Nos
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Microcephaly
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Psychomotor Development Impaired
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General disorders and administration site conditions
    Adverse Event Nos
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Allergy
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Drug Level Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Fever
         subjects affected / exposed
    5 / 13 (38.46%)
    4 / 10 (40.00%)
    6 / 20 (30.00%)
    5 / 12 (41.67%)
         occurrences all number
    19
    10
    16
    17
    Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    2 / 20 (10.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    3
    3
    Injury
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 10 (20.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    4
    2
    0
    0
    Infection Viral
         subjects affected / exposed
    5 / 13 (38.46%)
    2 / 10 (20.00%)
    5 / 20 (25.00%)
    1 / 12 (8.33%)
         occurrences all number
    11
    3
    6
    1
    Otitis Media
         subjects affected / exposed
    3 / 13 (23.08%)
    3 / 10 (30.00%)
    4 / 20 (20.00%)
    2 / 12 (16.67%)
         occurrences all number
    6
    5
    13
    9
    Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    1
    Bronchitis
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 10 (0.00%)
    6 / 20 (30.00%)
    2 / 12 (16.67%)
         occurrences all number
    3
    0
    10
    3
    Bronchospasm
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    2 / 20 (10.00%)
    2 / 12 (16.67%)
         occurrences all number
    2
    0
    4
    4
    Coughing
         subjects affected / exposed
    4 / 13 (30.77%)
    0 / 10 (0.00%)
    4 / 20 (20.00%)
    2 / 12 (16.67%)
         occurrences all number
    6
    0
    4
    3
    Dyspnoea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    4 / 13 (30.77%)
    0 / 10 (0.00%)
    2 / 20 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    2
    0
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    3
    1
    Pneumothorax
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory Disorder
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Rhinitis
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 10 (20.00%)
    5 / 20 (25.00%)
    3 / 12 (25.00%)
         occurrences all number
    4
    2
    6
    7
    Sinusitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    4
    0
    Stridor
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Upper Resp Tract Infection
         subjects affected / exposed
    5 / 13 (38.46%)
    3 / 10 (30.00%)
    9 / 20 (45.00%)
    6 / 12 (50.00%)
         occurrences all number
    12
    11
    12
    16
    Psychiatric disorders
    Anorexia
         subjects affected / exposed
    4 / 13 (30.77%)
    2 / 10 (20.00%)
    4 / 20 (20.00%)
    4 / 12 (33.33%)
         occurrences all number
    9
    4
    6
    7
    Insomnia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    2
    Nervousness
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    2 / 12 (16.67%)
         occurrences all number
    2
    0
    3
    2
    Somnolence
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 10 (30.00%)
    4 / 20 (20.00%)
    5 / 12 (41.67%)
         occurrences all number
    2
    5
    13
    9
    Cardiac disorders
    Hypertension
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    4
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Convulsions Aggravated
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    2
    Coordination Abnormal
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Hypertonia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypotonia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    2 / 20 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Granulocytopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Leucopenia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Eye disorders
    Vision Abnormal
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    3 / 12 (25.00%)
         occurrences all number
    2
    1
    0
    4
    Diarrhoea
         subjects affected / exposed
    5 / 13 (38.46%)
    2 / 10 (20.00%)
    2 / 20 (10.00%)
    5 / 12 (41.67%)
         occurrences all number
    5
    3
    4
    13
    Eructation
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Gastro-Intestinal Disorder Nos
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    1
    1
    Melaena
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Tooth Discolouration
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Stomatitis Ulcerative
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tooth Disorder
         subjects affected / exposed
    3 / 13 (23.08%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences all number
    6
    0
    3
    1
    Vomiting
         subjects affected / exposed
    7 / 13 (53.85%)
    2 / 10 (20.00%)
    3 / 20 (15.00%)
    5 / 12 (41.67%)
         occurrences all number
    17
    2
    6
    9
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gamma-Gt Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    2 / 20 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    4
    0
    SGOT Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 10 (20.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    3
    1
    2
    Hepatic Function Abnormal
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    SGPT Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Dermatitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    1
    Dermatitis Contact
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eczema
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    2
    0
    2
    Rash
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Rash Maculo-Papular
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Seborrhoea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Skin Discolouration
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin Dry
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Sweating Decreased
         subjects affected / exposed
    3 / 13 (23.08%)
    1 / 10 (10.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    5
    2
    1
    0
    Renal and urinary disorders
    Albuminuria
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    2
    0
    2
    Bladder Calculus
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    4
    0
    0
    1
    Haematuria
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    2
    0
    0
    2
    Hydronephrosis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Nephropathy Toxic
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oliguria
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Renal Calculus
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 10 (10.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    2
    1
    0
    Urine Abnormal
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    2
    2
    Urinary Tract Infection
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    4
    2
    0
    2
    Metabolism and nutrition disorders
    Alkalosis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Acidosis
         subjects affected / exposed
    6 / 13 (46.15%)
    4 / 10 (40.00%)
    6 / 20 (30.00%)
    4 / 12 (33.33%)
         occurrences all number
    13
    9
    8
    9
    Calcinosis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    7
    0
    0
    1
    Dehydration
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    2
    1
    Hyperchloraemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hyperammonaemia
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 10 (30.00%)
    4 / 20 (20.00%)
    4 / 12 (33.33%)
         occurrences all number
    3
    5
    7
    8
    Hyperkalaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    LDH Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Phosphatase Alkaline Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Weight Decrease
         subjects affected / exposed
    5 / 13 (38.46%)
    3 / 10 (30.00%)
    4 / 20 (20.00%)
    3 / 12 (25.00%)
         occurrences all number
    11
    9
    7
    10

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Apr 2005
    The overall reason for the amendment was to modify the timing of dosing, scheduling and time of admission to the study site on pharmacokinetic(s) (PK) visit days, and use of intravenous catheterization for PK assessments.
    04 May 2006
    The overall reason for the amendment was to incorporate feedback from investigators and regulatory authorities. Liberalization and clarification of enrollment criteria and laboratory alert parameters were made.

    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
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    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
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