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

Phase 2

Completed

• Conditions: Restless Legs Syndrome
• Interventions: Drug: Rotigotine

• Registration Number: NCT01495793
• Lead Sponsor: UCB BIOSCIENCES, Inc.

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2011-12-16
• Study First Submitted QC: 2011-12-16
• Study First Posted: 2011-12-20
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Results First Submitted: 2015-04-29
• Results First Submitted QC: 2015-06-17
• Results First Posted: 2015-07-14
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-08
• Last Update Posted: 2018-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rotigotine	Rotigotine	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.

Primary Outcome Measures

Name	Time	Method
Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 0.5 mg/24 h (2.5 cm^2)	0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28	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.
Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 2 mg/24 h (10 cm^2)	0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28	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.
Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 1 mg/24 h (5 cm^2)	0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28	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.
Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 1 mg/24 h (5 cm^2)	0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28	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.
Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 3 mg/24 h (15 cm^2)	0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28	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.
Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 0.5 mg/24 h (2.5 cm^2)	0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28	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.
Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 2 mg/24 h (10 cm^2)	0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28	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.
Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 3 mg/24 h (15 cm^2)	0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28	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.

Trial Locations

Locations (12)

Sp1004 012; 🇺🇸 Los Angeles, California, United States

Sp1004 007; 🇺🇸 West Seneca, New York, United States

Sp1004 013; 🇺🇸 Indianapolis, Indiana, United States

Sp1004 001; 🇺🇸 Destrehan, Louisiana, United States

Sp1004 005; 🇺🇸 Washington, District of Columbia, United States

Sp1004 016; 🇺🇸 West Chester, Pennsylvania, United States

Sp1004 006; 🇺🇸 Little Rock, Arkansas, United States

Sp1004 009; 🇺🇸 Orange, California, United States

Sp1004 014; 🇺🇸 Spring Hill, Florida, United States

Sp1004 015; 🇺🇸 Saint Louis, Missouri, United States

Sp1004 002; 🇺🇸 Cincinnati, Ohio, United States

Sp1004 003; 🇺🇸 Austin, Texas, United States