Dose Escalating Study of Rotigotine in Pediatric Subjects With Restless Legs Syndrome

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