Dose Escalating Study of Rotigotine in Pediatric Subjects With Restless Legs Syndrome
Condition: Restless Legs Syndrome
MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome
Intervention: Rotigotine
Intervention description: Rotigotine transdermal patch:
Dose (size): 0.5 mg/24 h (2.5 cm^2)- 1 mg/24 h (5 cm^2)- 2 mg/24 h (10 cm^2)- 3 mg/24 h (15 cm^2) The patch has to be applied continuously for 24h. After 24h, the patch has to be removed and a new one applied.
Intervention MeSH terms: Rotigotine
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 13 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Rotigotine; Restless Legs Syndrome; RLS; Children; Adolescents

Summary:

      This was a multicenter, open-label, dose-escalation, Phase 2A study with multiple
      administrations of the rotigotine transdermal system. The study was conducted in adolescent
      subjects (13 to <18 years of age) with idiopathic Restless Legs Syndrome (RLS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject or parent/legal representative is considered reliable and capable of adhering
             to the protocol

          -  Subject is male or female, and is ≥13 and <18 years of age at Visit 2/Baseline

          -  Subject weighs ≥40 kg at Visit 2/Baseline

          -  Subject's Body Mass Index (BMI) is less than the 95th percentile for his or her age at
             Visit 2/Baseline

          -  Subject meets the diagnosis of RLS based on the proposed 2011 Revised International
             Restless Legs Syndrome Study Group Diagnostic Criteria

          -  Subject's RLS symptoms cause significant distress or impairment

          -  At Visit 2/Baseline, subject has a Periodic Limb Movement Index (PLMI) ≥5 during at
             least 1 of the 5 nights prior to Baseline as measured by the activity monitors

          -  At Visit 2/Baseline, subject has a score of ≥15 on the IRLS Rating Scale

          -  At Visit 2/Baseline, subject scores ≥4 points on the Clinical Global Impression (CGI)
             Item 1 assessment

          -  Subject receiving supplemental iron has been on a stable dose for at least 3 months
             prior to Visit 1/Screening Period

        Exclusion Criteria:

          -  Previously participated in this study or received previous treatment with rotigotine

          -  Participated in another study of an investigational medicinal product (IMP) or a
             medical device within the last 3 months prior to Visit 1/Screening Period or is
             currently participating in another study of an IMP or a medical device

          -  Subject's RLS symptoms are restricted only to the ankles or knees

          -  RLS symptoms are due to renal insufficiency (uremia) or iron deficiency anemia

          -  Previous treatment with dopamine agonists within a period of 14 days prior to Visit
             2/Baseline or L-dopa within 7 days prior to Visit 2/Baseline

          -  Failed to respond to previous dopaminergic therapy

          -  Any medical or psychiatric condition, which in the opinion of the investigator, would
             jeopardize or compromise the subject's well being or ability to participate

          -  Subject has a lifetime history of suicide attempt or has suicidal ideation in the past
             6 months

          -  Evidence of an impulse control disorder (ICD)

          -  History or current symptoms of sleep apnea, narcolepsy, sleep attacks/sudden onset of
             sleep, or myoclonus epilepsy

          -  Concomitant diseases such as peripheral neuropathy, muscle fasciculation, painful legs
             and moving toes, fibromyalgia, rheumatoid arthritis, or sickle cell disease

          -  Serum ferritin level <15 ng/mL

          -  Subject has not attempted at least 1 non-pharmacological intervention for the
             management of RLS (eg, sleep hygiene, exercise)

          -  Prior history of psychotic episodes

          -  History of chronic alcohol or drug abuse within 12 months prior Screening Period

          -  Clinically relevant cardiac dysfunction and/or arrhythmias

          -  Hemoglobin level below the lower limit of normal

          -  Clinically relevant renal dysfunction (serum creatinine >1.5 mg/dL)

          -  Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin
             level greater than or equal to 2 times the upper limit of normal

          -  History or presence of clinical signs of any malignant neoplasm including suspicious
             undiagnosed skin lesion (which may be melanoma), melanoma, or a history of melanoma

          -  Currently receiving or has received treatment with any of the following within 28 days
             prior to Visit 2/Baseline: neuroleptics, antidepressants, anxiolytic drugs, opioids,
             monoamine oxidase (MAO) inhibitors, or sedative antihistamines

          -  Currently receiving treatment with any of the following: benzodiazepines, hypnotics,
             anticonvulsants, central alpha-adrenergic agonists, or melatonin; unless treatment is
             for RLS only, in which case a Wash-Out Period of at least 14 days prior to Visit
             2/Baseline is required

          -  Currently receiving stimulant therapy for attention deficit hyperactivity disorder
             (ADHD); a Wash-Out Period of at least 7 days prior to Visit 2/Baseline is required

          -  Pregnant, nursing, or is a woman of childbearing potential who is not surgically
             sterile, or does not consistently use 2 combined medically acceptable methods of
             contraception (including at least 1 barrier method), unless not sexually active

          -  Unwilling to abstain from caffeine after 4pm each evening within 7 days prior to Visit
             2/Baseline and for the duration of the study

          -  Pursues shift work or performs other continuous non-disease-related life conditions,
             which do not allow regular sleep at night

          -  Subject has a QT correction (QTc) interval of ≥500 ms at Visit 1/Screening Period or
             Visit 2/Baseline. Bazett's correction method must be used for the correction of the QT
             interval

          -  Symptomatic orthostatic hypotension with a decrease of blood pressure (BP) from supine
             to standing position of ≥20 mmHg in systolic blood pressure (SBP) or of ≥10 mmHg in
             diastolic blood pressure (DBP) taken from the 5 minute supine and 1 and/or 3 minute
             standing measurements

          -  A known hypersensitivity to any of the components of the study medication, such as a
             history of significant skin hypersensitivity to adhesives, known hypersensitive