Clinical trial NCT01495793: Dose Escalating Study of Rotigotine in Pediatric Subjects With Restless Legs Syndrome
Official title: A Multicenter, Open-Label, 2-Group, Dose Escalation Study of Monotherapy Administration of Rotigotine in Pediatric Subjects With Idiopathic Restless Legs Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Restless Legs Syndrome
Keywords: Rotigotine
Restless Legs Syndrome
RLS
Children
Adolescents
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2011-12-20
Enrollment: 42
Sex: ALL
Minimum age (years): 13
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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

Primary outcomes:
measure: Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 0.5 mg/24 h (2.5 cm^2)
timeFrame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
measure: Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 1 mg/24 h (5 cm^2)
timeFrame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
measure: Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 2 mg/24 h (10 cm^2)
timeFrame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
measure: Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 3 mg/24 h (15 cm^2)
timeFrame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
measure: Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 0.5 mg/24 h (2.5 cm^2)
timeFrame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
measure: Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 1 mg/24 h (5 cm^2)
timeFrame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
measure: Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 2 mg/24 h (10 cm^2)
timeFrame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
measure: Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 3 mg/24 h (15 cm^2)
timeFrame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Sp1004 006
state: Arkansas
city: Los Angeles
country: United States
facility: Sp1004 012
state: California
city: Orange
country: United States
facility: Sp1004 009
state: California
city: Washington
country: United States
facility: Sp1004 005
state: District of Columbia
city: Spring Hill
country: United States
facility: Sp1004 014
state: Florida
city: Indianapolis
country: United States
facility: Sp1004 013
state: Indiana
city: Destrehan
country: United States
facility: Sp1004 001
state: Louisiana
city: Saint Louis
country: United States
facility: Sp1004 015
state: Missouri
city: West Seneca
country: United States
facility: Sp1004 007
state: New York
city: Cincinnati
country: United States
facility: Sp1004 002
state: Ohio
city: West Chester
country: United States
facility: Sp1004 016
state: Pennsylvania
city: Austin
country: United States
facility: Sp1004 003
state: Texas
Study officials:
affiliation: 1-877-822-9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Elshoff JP, Hudson J, Picchietti DL, Ridel K, Walters AS, Doggett K, Moran K, Oortgiesen M, Ramirez F, Schollmayer E. Pharmacokinetics of rotigotine transdermal system in adolescents with idiopathic restless legs syndrome (Willis-Ekbom disease). Sleep Med. 2017 Apr;32:48-55. doi: 10.1016/j.sleep.2016.04.012. Epub 2016 Jun 8.