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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35495   clinical trials with a EudraCT protocol, of which   5837   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).
     
    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:
    A Multicenter, Open-Label, 2-Group, Dose Escalation Study of Monotherapy Administration of Rotigotine in Pediatric Subjects With Idiopathic Restless Legs Syndrome

    Summary
    EudraCT number
    2014-004383-37
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    30 Apr 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    30 Jun 2016
    First version publication date
    03 Jul 2015
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    SP1004
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01495793
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB Biosciences Inc.
    Sponsor organisation address
    8010 Arco Corporate Drive, Raleigh, United States, NC 27617
    Public contact
    CTRRD, UCB Biosciences GmbH, +49 2173481515, clinicaltrials@ucb.com
    Scientific contact
    CTRRD, UCB Biosciences GmbH, +49 2173481515, clinicaltrials@ucb.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
    13 Aug 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Apr 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Apr 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to determine the pharmacokinetic (PK) properties of rotigotine in adolescents with idiopathic restless legs syndrome (RLS) after multiple patch administrations.
    Protection of trial subjects
    Close monitoring of subjects safety status, including checks of mental health e.g. by CSSR-S questionnaire.
    Background therapy
    If nausea or vomiting occurred during the study, antiemetic therapy with ondansetron was allowed. Ondansetron was not to be used prophylactically. Use of a topical anesthetic was permitted to treat the venous puncture or indwelling venous catheter site prior to the needle stick. If medication is medically indicated, the subject must inform the investigator immediately. All concomitant medication and treatment was recorded in the appropriate study documents (i.e. eCRF and source document).
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    01 Dec 2011
    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
    United States: 24
    Worldwide total number of subjects
    24
    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)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    24
    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
    This was a multicenter study in which 42 subjects were enrolled and 24 treated at 8 sites in the USA.

    Pre-assignment
    Screening details
    In total 42 subjects signed the informed consent and were enrolled into the study (Enrolled Set). 24 of these subjects were treated with medication. The sample size of 24 subjects was sufficient to target a 95% confidence interval and the calculation was based on a previous study. Participant Flow refers to the 24 treated subjects (Safety Set).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Rotigotine
    Arm description
    In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Neupro 0.5 mg/24 h
    Investigational medicinal product code
    Prod 1
    Other name
    Pharmaceutical forms
    Transdermal patch
    Routes of administration
    Transdermal use
    Dosage and administration details
    In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks. Dose (size): 0.5 mg/24 h (2.5 cm^2) The patch has to be applied continuously for 24h. After 24h, the patch has to be removed and a new one applied.

    Investigational medicinal product name
    Neupro 1 mg/24 h
    Investigational medicinal product code
    Prod 2
    Other name
    Pharmaceutical forms
    Transdermal patch
    Routes of administration
    Transdermal use
    Dosage and administration details
    In the Titration Period a subject received the first dose of rotigotine than the dose was increased weekly by a dose step over 4 weeks. Dose (size): 1 mg/24 h (5 cm^2) The patch has to be worn continuously for 24h. After 24h, the patch has to be removed and a new one applied.

    Investigational medicinal product name
    Neupro 3 mg/24 h
    Investigational medicinal product code
    Prod 4
    Other name
    Pharmaceutical forms
    Transdermal patch
    Routes of administration
    Transdermal use
    Dosage and administration details
    In the Titration Period a subject received the first dose of rotigotine than the dose was increased weekly by a dose step over 4 weeks. Dose (size): 3 mg/24 h (15 cm^2) The patch has to be worn continuously for 24h. After 24h, the patch has to be removed and a new one applied.

    Investigational medicinal product name
    Neupro 2 mg/24 h
    Investigational medicinal product code
    Prod 3
    Other name
    Pharmaceutical forms
    Transdermal patch
    Routes of administration
    Transdermal use
    Dosage and administration details
    In the Titration Period a subject received the first dose of rotigotine than the dose was increased weekly by a dose step over 4 weeks. Dose (size): 2 mg/24 h (10 cm^2 The patch has to be worn continuously for 24h. After 24h, the patch has to be removed and a new one applied.

    Number of subjects in period 1
    Rotigotine
    Started
    24
    Completed
    22
    Not completed
    2
         Violation of inclusion criteria
    1
         Lost to follow-up
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Rotigotine
    Reporting group description
    In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.

    Reporting group values
    Rotigotine Total
    Number of subjects
    24 24
    Age categorical
    Units: Subjects
        13 years
    2 2
        14 years
    6 6
        15 years
    6 6
        16 years
    4 4
        17 years
    6 6
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    15.3 ± 1.3 -
    Gender Categorical
    Units: Subjects
        Male
    9 9
        Female
    15 15
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0
        Asian
    0 0
        Black or African American
    8 8
        Native Hawaiian or Other Pacific Islander
    0 0
        White
    16 16
        More than one race
    0 0
        Unknown or Not Reported
    0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Not Hispanic or Latino
    20 20
        Hispanic or Latino
    4 4
        Unknown or Not Reported
    0 0
    Height
    Units: cm
        arithmetic mean (standard deviation)
    167.39 ± 6.89 -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    65.7 ± 10.72 -
    BMI (Body Mass Index)
    Units: kg/m^2
        arithmetic mean (standard deviation)
    23.388 ± 3.133 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Rotigotine
    Reporting group description
    In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.

    Subject analysis set title
    Rotigotine (PKPPS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Pharmacokinetic Per Protocol Set (PKPPS) includes all enrolled subjects who were included in the Safety Set, who had no protocol deviations that were considered to impact the subject's validity for analysis of the primary study objective and who for at least 1 dose step fulfilled specific predefined conditions.

    Primary: Apparent Total Body Clearance (Cl/f) of unconjugated rotigotine 0.5 mg/24 h (2.5 cm^2)

    Close Top of page
    End point title
    Apparent Total Body Clearance (Cl/f) of unconjugated rotigotine 0.5 mg/24 h (2.5 cm^2) [1]
    End point description
    CL/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma. For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.
    End point type
    Primary
    End point timeframe
    0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
    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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Rotigotine (PKPPS)
    Number of subjects analysed
    6
    Units: L/h (liter per hour)
    least squares mean (confidence interval 95%)
        Apparent Total Body Clearance
    676.86 (408.5 to 1121.51)
    No statistical analyses for this end point

    Primary: Apparent Total Body Clearance (Cl/f) of unconjugated rotigotine 1 mg/24 h (5 cm^2)

    Close Top of page
    End point title
    Apparent Total Body Clearance (Cl/f) of unconjugated rotigotine 1 mg/24 h (5 cm^2) [2]
    End point description
    CL/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma. For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.
    End point type
    Primary
    End point timeframe
    0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
    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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Rotigotine (PKPPS)
    Number of subjects analysed
    10
    Units: L/h (Liter per hour)
    least squares mean (confidence interval 95%)
        Apparent Total Body Clearance
    671.72 (459.11 to 982.8)
    No statistical analyses for this end point

    Primary: Apparent Total Body Clearance (Cl/f) of unconjugated rotigotine 2 mg/24 h (10 cm^2)

    Close Top of page
    End point title
    Apparent Total Body Clearance (Cl/f) of unconjugated rotigotine 2 mg/24 h (10 cm^2) [3]
    End point description
    CL/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma. For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.
    End point type
    Primary
    End point timeframe
    0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
    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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Rotigotine (PKPPS)
    Number of subjects analysed
    11
    Units: L/h (Liter per hour)
    least squares mean (confidence interval 95%)
        Apparent Total Body Clearance
    937.56 (658.5 to 1334.89)
    No statistical analyses for this end point

    Primary: Apparent Total Body Clearance (Cl/f) of unconjugated rotigotine 3 mg/24 h (15 cm^2)

    Close Top of page
    End point title
    Apparent Total Body Clearance (Cl/f) of unconjugated rotigotine 3 mg/24 h (15 cm^2) [4]
    End point description
    CL/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma. For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.
    End point type
    Primary
    End point timeframe
    0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
    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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Rotigotine (PKPPS)
    Number of subjects analysed
    9
    Units: L/h (Liter per hour)
    least squares mean (confidence interval 95%)
        Apparent Total Body Clearance
    1088.77 (723.47 to 1638.53)
    No statistical analyses for this end point

    Primary: Volume of Distribution at steady state (VSS/f) of unconjugated rotigotine 0.5 mg/24 h (2.5 cm^2)

    Close Top of page
    End point title
    Volume of Distribution at steady state (VSS/f) of unconjugated rotigotine 0.5 mg/24 h (2.5 cm^2) [5]
    End point description
    VSS/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma. For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.
    End point type
    Primary
    End point timeframe
    0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
    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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Rotigotine (PKPPS)
    Number of subjects analysed
    6
    Units: L (Liter)
    least squares mean (confidence interval 95%)
        Volume of Distribution at steady state
    5403.16 (2850.67 to 10241.17)
    No statistical analyses for this end point

    Primary: Volume of Distribution at steady state (VSS/f) of unconjugated rotigotine 1 mg/24 h (5 cm^2)

    Close Top of page
    End point title
    Volume of Distribution at steady state (VSS/f) of unconjugated rotigotine 1 mg/24 h (5 cm^2) [6]
    End point description
    VSS/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma. For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.
    End point type
    Primary
    End point timeframe
    0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
    Notes
    [6] - 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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Rotigotine (PKPPS)
    Number of subjects analysed
    10
    Units: L (Liter)
    least squares mean (confidence interval 95%)
        Volume of Distribution at steady state
    6220.79 (3842.05 to 10072.28)
    No statistical analyses for this end point

    Primary: Volume of Distribution at steady state (VSS/f) of unconjugated rotigotine 2 mg/24 h (10 cm^2)

    Close Top of page
    End point title
    Volume of Distribution at steady state (VSS/f) of unconjugated rotigotine 2 mg/24 h (10 cm^2) [7]
    End point description
    VSS/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma. For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.
    End point type
    Primary
    End point timeframe
    0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
    Notes
    [7] - 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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Rotigotine (PKPPS)
    Number of subjects analysed
    11
    Units: L (Liter)
    least squares mean (confidence interval 95%)
        Volume of Distribution at steady state
    7114.01 (4547.88 to 11128.07)
    No statistical analyses for this end point

    Primary: Volume of Distribution at steady state (VSS/f) of unconjugated rotigotine 3 mg/24 h (15 cm^2)

    Close Top of page
    End point title
    Volume of Distribution at steady state (VSS/f) of unconjugated rotigotine 3 mg/24 h (15 cm^2) [8]
    End point description
    VSS/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma. For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.
    End point type
    Primary
    End point timeframe
    0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
    Notes
    [8] - 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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Rotigotine (PKPPS)
    Number of subjects analysed
    9
    Units: L (Liter)
    least squares mean (confidence interval 95%)
        Volume of Distribution at steady state
    6037.92 (3598.36 to 10131.41)
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    9.1
    Reporting groups
    Reporting group title
    Rotigotine
    Reporting group description
    In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.

    Serious adverse events
    Rotigotine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 24 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Rotigotine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 24 (62.50%)
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Stress fracture
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Road traffic accident
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Wound
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2
    Immune system disorders
    Allergy to arthropod sting
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Food allergy
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Headache
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2
    Syncope
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Dizzines
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2
    Migraine
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Sudden onset of sleep
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    2
    General disorders and administration site conditions
    Application site irritation
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Application site pruritus
         subjects affected / exposed
    4 / 24 (16.67%)
         occurrences all number
    4
    Irritability
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Nausea
         subjects affected / exposed
    7 / 24 (29.17%)
         occurrences all number
    11
    Vomiting
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Urticaria
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Muscular weakness
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Muscukoseletal pain
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Neck pain
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Pain in extremity
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Increased appetite
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Anorexia
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Fungal infection
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Nasopharyngitis
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    3
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Pharyngitis
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Mar 2011
    The main purpose of this substantial amendment was to include the suicidality risk assessment (Columbia-Suicide Severity Rating Scale [C-SSRS]). In accordance with the FDA draft Guidance for Industry, which went into effect on 29 Oct 2010. In addition, a list of anticipated serious adverse events (SAEs) was included in this amendment in compliance with the recent FDA guidance on safety reporting requirements for studies conducted under an open Investigational New Drug Application. The Beck Depression Inventory II and the Beck Anxiety Inventory were removed from the study assessments. Other changes included in this amendment were as follows: - Procedures for subjects wishing to enter the open-label, LTFU study (SP1005) following dose de-escalation but prior to the SFU Visit were added. - Definition of clinically relevant renal dysfunction at Visit 1/Screening Period as an exclusion criterion was increased from serum creatinine >1.0mg/dL to >1.5mg/dL since the previous serum creatinine level >1.0mg/dL was within the central laboratory’s normal range. Physical examination was removed as a safety variable. - The version number of the Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale was added. - For clarity, a dose de-escalation table (Table 3-3) was added. - Storage requirements for the rotigotine patch were updated. - Use of a topical anesthetic prior to the needle stick was permitted. - Corrections were made to the definitions of some PK parameters, as well as the preparation and handling of the blood and saliva PK samples. - Reference to patch size was removed from all sections, except Section 7.1 of the protocol, Description of investigational medicinal product (IMP). - Vital sign parameters to be measured were specified as pulse rate, SBP, DBP, and orthostatic hypertension assessments. - Sponsor Clinical Project Manager contact information was updated. - Typographic errors and changes of an editorial nature were made.
    19 Sep 2011
    The purpose of this substantial amendment was to increase the minimum weight for enrollment in the study from 30kg to 40kg. An additional change clarifying that subjects must tolerate the first dose step to be able to transition into the open-label, LTFU study was also made.
    02 May 2012
    The main purpose of this substantial amendment was to ensure consistency between the protocol and the FDA Pediatric Development Plan for the RLS indication in subjects 13 to <18 years of age. Since the subject’s dosing was no longer dependent on body weight, the dosing schedules for each study period were revised. The primary PK variables were changed to reflect those that were requested by the FDA for the revised sample size calculation. In addition, PK saliva sampling was removed from the study. Data from a recently completed PK study (RL0002) suggest that saliva concentrations of rotigotine cannot be used as a surrogate for plasma concentrations of rotigotine. Other changes included in this amendment were as follows: - Updated contact information for SAE reporting and procedures for reporting SAEs to be consistent with the current protocol template. - Updated the regulatory status of rotigotine for the treatment of RLS in adults in the US. - Removed the requirement for the PK blood samples to be centrifuged at a controlled temperature. - Corrected typographic errors and minor inconsistencies of an editorial nature.

    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA