Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Vergleich der Wirksamkeit von Medikinet retard mit Concerta bei Kindern mit ADHS Comparison of the efficacy of Medikinet® retard with Concerta in children with ADHD

    Summary
    EudraCT number
    		 2005-003295-38
    Trial protocol
    		 DE  
    Global end of trial date
    27 Mar 2009

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Jul 2016
    First version publication date
    20 Jul 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    6520-0650-07
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MEDICE Arzneimittel Pütter GmbH & Co. KG
    Sponsor organisation address
    Kuhloweg 38, Iserlohn, Germany, 58638
    Public contact
    Medical Department, MEDICE Arzneimittel Pütter GmbH & Co KG, info@medice.de
    Scientific contact
    Medical Department, MEDICE Arzneimittel Pütter GmbH & Co KG, info@medice.de
    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
    27 Mar 2009
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Mar 2009
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Mar 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The aim of this study was to compare Medikinet® retard in various doses with Concerta® in relation to efficacy variables in children with ADHD
    Protection of trial subjects
    Safety assessments included of monitoring and recording all adverse events and serious adverse events, the regular measurement of vital signs and using a questionnaire about possible side effects of drugs (ADHS-TAP)
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Aug 2006
    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
    Germany: 113
    Worldwide total number of subjects
    113
    EEA total number of subjects
    113
    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)
    81
    Adolescents (12-17 years)
    32
    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
    		 Male and female patients were included aged 6 to 17 years 11 months. A prerequisite was that the patient attended a primary, secondary or special school and had a class teacher, or attended the HEBO School in Bonn or had been attending a hospital school in a paediatric psychiatry clinic for at least 3 weeks.

    Pre-assignment
    Screening details
    		 122 subjects were screened and 113 subjects were enrolled in this study from 9 study center.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Subject, Data analyst, Carer
    Blinding implementation details
    For Concerta and Medikinet retard, capsules were made to order so they appeared identically.

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Medikinet retard equivalent dose
    Arm description
    		 Medikinet retard in a approximately equivalent dose to Concerta per dose per day (20 or 30 mg)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Medikinet retard 20 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    20 mg methylphenidate hydrochloride

    Investigational medicinal product name
    Medikinet retard 30 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    30 mg methylphenidate hydrochloride

    Arm title
    		 Medikinet retard lower dose
    Arm description
    		 Medikinet retard in lower daily dose (10 or 20 mg)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Medikinet retard 20 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    20 mg m ethylphenidate hydrochloride

    Investigational medicinal product name
    Medikinet retard 10 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    10 mg methylphenidate hydrochloride

    Arm title
    		 Concerta
    Arm description
    		 Concerta (18 or 36 mg)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Concerta 18 mg or 36 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    18 mg methylphenidatehydrochloride

    Number of subjects in period 1
    		Medikinet retard equivalent dose Medikinet retard lower dose Concerta
    Started
    108
    106
    110
    Completed
    106
    99
    104
    Not completed
    2
    7
    6
         Adverse event, non-fatal
    -
    3
    1
         Teacher ill
    -
    1
    -
         Lack of compliance of the teacher
    -
    1
    3
         Protocol deviation
    1
    2
    2
         Lack of efficacy
    1
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Period
    Reporting group description
    		 86 of 113 patients were male. The mean Age was 10

    Reporting group values
    		 Overall Period Total
    Number of subjects
    		 113 113
    Age categorical
    Units: Subjects
        Children (6-9)
    		 51 51
        Children (10-12)
    		 43 43
        Adolescents (13-17)
    		 19 19
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 10.2 ( 2.3 ) -
    Gender categorical
    86 males and 27 females
    Units: Subjects
        Male
    		 86 86
        Female
    		 27 27

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Medikinet retard equivalent dose
    Reporting group description
    		 Medikinet retard in a approximately equivalent dose to Concerta per dose per day (20 or 30 mg)

    Reporting group title
    Medikinet retard lower dose
    Reporting group description
    		 Medikinet retard in lower daily dose (10 or 20 mg)

    Reporting group title
    Concerta
    Reporting group description
    		 Concerta (18 or 36 mg)

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Every patient who had taken the investigational drug at least once and for whom there were data for the pairwise intraindividual comparison relating to a SKAMP-D score was accepted into the cohort for confirmatory analysis. In the following text, deviating from the usual definitions, this sample of 107 patients is called the ITT cohort. If, in tables, smaller numbers of cases than n=107 appear, they refer in each case to the data available for the particular variable.

    Subject analysis set title
    PP
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The 91 patients who did not discontinue the study and who could be evaluated as "per protocol" are called the PP cohort in the following text. If, in tables, smaller numbers of cases than n=91 appear, they refer in each case to the data available for the particular variable

    Primary: Skamp-D in the first 3 school hours; Test H0A Test for non-inferiority of Medikinet retard in equivalent dose vs. Concerta

    		 Close Top of page
    End point title
    		 Skamp-D in the first 3 school hours; Test H0A Test for non-inferiority of Medikinet retard in equivalent dose vs. Concerta [1]
    End point description
    In patients with ADHD, diagnosed using DCL-HKS, an equivalent dose of Medikinet® retard compared with an appropriate dose of Concerta® gives the same or insignificantly poorer results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school, accepting a non-inferiority limit of Delta=+0.167. The null hypothesis H0A could be ruled out at a level of significance of alpha0.025 (one-sided) (p<0.0001; test according to Duchateau et al., 2002). Consequently it could be demonstrated that an approximately equivalent daily dose of Medikinet® retard compared with an appropriate dose of Concerta® gave the same and/or insignificantly poorer results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school. The one-sided 97.5% confidence interval was ( minus infinity;-0.217). Handling for missing data is described in detail in the free available publication.
    End point type
    Primary
    End point timeframe
    Baseline and after each visit
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Due to cross-over design. Almost all patients were included in each Group/Treatment Arm
    End point values
    		 Medikinet retard equivalent dose Concerta
    Number of subjects analysed
    99 [2]
    101 [3]
    Units: points
        arithmetic mean (standard error)
    0.6 ( 0.06 )
    0.76 ( 0.05 )
    Notes
    [2] - Teacher did not complete the SKAMP
    [3] - Teacher did not complete the SKAMP
    Statistical analysis title
    		 H0A: non-inferiority equivalent dose of Medikinet®
    Statistical analysis description
    Null hypothesis A: H0A In patients with ADHD, diagnosed using DCL-HKS, an equivalent dose of Medikinet® retard compared with an appropriate dose of Concerta® gives poorer results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school, accepting a non-inferiority limit of Delta0.167.
    Comparison groups
    Medikinet retard equivalent dose v Concerta
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    P-value
    		 < 0.0001
    Method
    		 Duchateau 2002
    Parameter type
    		 Effect estimators
    Confidence interval
         level
    		 97.5%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -0.217
    Notes
    [4] - The null hypothesis H0A could be ruled out at a level of significance of alpha=0.025 (one-sided) (p<0.0001; test according to Duchateau et al., 2002). Consequently it could be demonstrated that an approximately equivalent daily dose of Medikinet® retard compared with an appropriate dose of Concerta® gave the same and/or insignificantly poorer results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school. The one-sided 97.5% confidence interval was (-infinity,-0.217.

    Primary: SKAMP-D in the first 3 school hours H0B1 Test for superiority of Medikinet retard in approximately equivalent daily dose vs. Concerta

    		 Close Top of page
    End point title
    		 SKAMP-D in the first 3 school hours H0B1 Test for superiority of Medikinet retard in approximately equivalent daily dose vs. Concerta [5]
    End point description
    In patients with ADHD, diagnosed using DCL-HKS, an equivalent dose of Medikinet® retard compared with an appropriate dose of Concerta® gives the same or poorer results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school. Alternative hypothesis B1: H1B1 In patients with ADHD, diagnosed using DCL-HKS, an equivalent dose of Medikinet® retard compared with an appropriate dose of Concerta® gives better results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school. The null hypothesis H0B1 could be ruled out (p=0.0009; test according to Duchateau et al., 2002). It could thus be shown that an equivalent dose of Medikinet® retard compared with an appropriate dose of Concerta® gives better results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school. Handling for missing data is described in detail in the free available publication.
    End point type
    Primary
    End point timeframe
    reported at each visit
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Due to cross-over design. Almost all patients were included in each Group/Treatment Arm
    End point values
    		 Medikinet retard equivalent dose Concerta
    Number of subjects analysed
    99 [6]
    101 [7]
    Units: points
        arithmetic mean (standard error)
    0.6 ( 0.06 )
    0.76 ( 0.05 )
    Notes
    [6] - Teacher did not complete the SKAMP
    [7] - Teacher did not complete the SKAMP
    Statistical analysis title
    		 H0B1 Medikinet ret.in equivalent dose vs. Concerta
    Statistical analysis description
    Once the non-inferiority (hypotheses A) could be shown, hypothesis B1 (the superiority of the virtually equivalent daily dose of Medikinet® retard over an appropriate dose of Concerta®) and hypothesis B2 (the non-inferiority of the lower daily dose of Medikinet® retard to an appropriate dose of Concerta® with a non-inferiority limit of =0.167) were tested hierarchically, for the primary parameter, the SKAMP-D teacher ratings taken as mean values for the first 3 hours of school.
    Comparison groups
    Concerta v Medikinet retard equivalent dose
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 = 0.0009
    Method
    		 Duchateau
    Confidence interval
    Notes
    [8] - The null hypothesis H0B1 could be ruled out (p=0.0009; test according to Duchateau et al., 2002). It could thus be shown that an equivalent dose of Medikinet® retard compared with an appropriate dose of Concerta® gives better results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school.

    Primary: Skamp-D in the first 3 school hours H0B2 Test for non-inferiority of Medikinet retard in the reduced daily dose vs. Concerta

    		 Close Top of page
    End point title
    		 Skamp-D in the first 3 school hours H0B2 Test for non-inferiority of Medikinet retard in the reduced daily dose vs. Concerta [9]
    End point description
    In patients with ADHD, diagnosed using DCL-HKS, a lower dose of Medikinet® retard compared with an appropriate dose of Concerta® gives the same or insignificantly poorer results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school, accepting a non-inferiority limit of Delta =0.167. The null hypothesis H0B2 could be ruled out (p=0.0001; test according to Duchateau et al., 2002). It could thus be shown that a lower dose of Medikinet® retard gives the same or only insignificantly poorer results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school. The one-sided 97.5% confidence interval was (minus infinity;+ 0.051. To sum up it can be said that all the null hypotheses were rejected in the confirmatory analysis and that Medikinet® retard proved to be – at least in the first 3 hours of school and referring to the SKAMP-D – as effective as Concerta®.
    End point type
    Primary
    End point timeframe
    reported at each visit
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Due to cross-over design. Almost all patients were included in each Group/Treatment Arm
    End point values
    		 Medikinet retard lower dose Concerta
    Number of subjects analysed
    104 [10]
    101 [11]
    Units: points
        arithmetic mean (standard error)
    0.67 ( 0.06 )
    0.76 ( 0.05 )
    Notes
    [10] - Teacher did not complete the SKAMP
    [11] - Teacher did not complete the SKAMP
    Statistical analysis title
    		 H0B2 Medikinet retard in reduced dose vs. Concerta
    Statistical analysis description
    In patients with ADHD, diagnosed using DCL-HKS, a lower dose of Medikinet® retard compared with an appropriate dose of Concerta® gives poorer results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school, accepting a non-inferiority limit of Delta =0.167.
    Comparison groups
    Medikinet retard lower dose v Concerta
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [12]
    P-value
    		 < 0.0001
    Method
    		 Duchateau 2002
    Confidence interval
         level
    		 97.4%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 0.051
    Notes
    [12] - The null hypothesis H0B2 could be ruled out (p=0.0001; test according to Duchateau et al., 2002). It could thus be shown that a lower dose of Medikinet® retard compared with an appropriate dose of Concerta® gives the same or only insignificantly poorer results in SKAMP-D teacher ratings taken as mean values over the first 3 hours of school. The one-sided 97.5% confidence interval was (minus infinity, + 0.051.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    overall including baseline
    Adverse event reporting additional description
    In addition to the AEs documented by the doctors, side effects were systematically recorded using the ADHD-TAP. These weekly rating forms for the teachers and parents contain the essential aspects of the Observer Rating form for ADHD, the Observer Rating form for Social Conduct Disorders and the Side Effect Rating Scale. These are not reported here
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12.0
    Reporting groups
    Reporting group title
    Medikinet retard in equivalent dose
    Reporting group description
    		 -

    Reporting group title
    Medikinet in lower dose
    Reporting group description
    		 -

    Reporting group title
    Concerta
    Reporting group description
    		 -

    Serious adverse events
    		 Medikinet retard in equivalent dose Medikinet in lower dose Concerta
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 106 (0.00%)
    0 / 110 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 4.4%
    Non-serious adverse events
    		 Medikinet retard in equivalent dose Medikinet in lower dose Concerta
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    33 / 108 (30.56%)
    40 / 106 (37.74%)
    39 / 110 (35.45%)
    Investigations
    Weight loss
         subjects affected / exposed
    0 / 108 (0.00%)
    3 / 106 (2.83%)
    2 / 110 (1.82%)
         occurrences all number
    0
    3
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    8 / 108 (7.41%)
    3 / 106 (2.83%)
    10 / 110 (9.09%)
         occurrences all number
    8
    3
    10
    Disturbance in attention
         subjects affected / exposed
    0 / 108 (0.00%)
    3 / 106 (2.83%)
    5 / 110 (4.55%)
         occurrences all number
    0
    3
    5
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 108 (0.00%)
    4 / 106 (3.77%)
    3 / 110 (2.73%)
         occurrences all number
    0
    4
    3
    Gastrointestinal disorders
    Gastrointestinal pain
         subjects affected / exposed
    6 / 108 (5.56%)
    7 / 106 (6.60%)
    5 / 110 (4.55%)
         occurrences all number
    6
    7
    5
    Psychiatric disorders
    Initial insomnia
         subjects affected / exposed
    3 / 108 (2.78%)
    3 / 106 (2.83%)
    6 / 110 (5.45%)
         occurrences all number
    3
    3
    6
    Aggression
         subjects affected / exposed
    2 / 108 (1.85%)
    3 / 106 (2.83%)
    5 / 110 (4.55%)
         occurrences all number
    2
    3
    5
    Restlessness
         subjects affected / exposed
    1 / 108 (0.93%)
    5 / 106 (4.72%)
    2 / 110 (1.82%)
         occurrences all number
    1
    5
    2
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 108 (1.85%)
    2 / 106 (1.89%)
    1 / 110 (0.91%)
         occurrences all number
    2
    2
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 108 (2.78%)
    3 / 106 (2.83%)
    7 / 110 (6.36%)
         occurrences all number
    3
    3
    7

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Aug 2006
    Inclusion criteria "The patient was taking at least methylphenidate rapid release twice daily or Concerta or Medikinet retard once daily" was changed in: "The patient was taking at least methylphenidate rapid release twice daily or a methlyphenidate retard preparation once daily (e.g. Medikinet retard, / Ritalin SR / Metadate CD)"

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/21790298
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 07:14:25 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA