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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES, Inc. )
ClinicalTrials.gov Identifier:
NCT01495793
First received: December 16, 2011
Last updated: June 17, 2015
Last verified: June 2015
  Purpose

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).


Condition Intervention Phase
Restless Legs Syndrome
Drug: Rotigotine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Multicenter, Open-Label, 2-Group, Dose Escalation Study of Monotherapy Administration of Rotigotine in Pediatric Subjects With Idiopathic Restless Legs Syndrome

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 0.5 mg/24 h (2.5 cm^2) [ Time Frame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28 ] [ Designated as safety issue: No ]

    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 1 mg/24 h (5 cm^2) [ Time Frame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28 ] [ Designated as safety issue: No ]

    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) [ Time Frame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28 ] [ Designated as safety issue: No ]

    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) [ Time Frame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28 ] [ Designated as safety issue: No ]

    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) [ Time Frame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28 ] [ Designated as safety issue: No ]

    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 1 mg/24 h (5 cm^2) [ Time Frame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28 ] [ Designated as safety issue: No ]

    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) [ Time Frame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28 ] [ Designated as safety issue: No ]

    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) [ Time Frame: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28 ] [ Designated as safety issue: No ]

    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.



Enrollment: 42
Study Start Date: December 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Rotigotine

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.


  Eligibility

Ages Eligible for Study:   13 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01495793

Locations
United States, Arkansas
Sp1004 006
Little Rock, Arkansas, United States
United States, California
Sp1004 012
Los Angeles, California, United States
Sp1004 009
Orange, California, United States
United States, District of Columbia
Sp1004 005
Washington, District of Columbia, United States
United States, Florida
Sp1004 014
Spring Hill, Florida, United States
United States, Indiana
Sp1004 013
Indianapolis, Indiana, United States
United States, Louisiana
Sp1004 001
Destrehan, Louisiana, United States
United States, Missouri
Sp1004 015
Saint Louis, Missouri, United States
United States, New York
Sp1004 007
West Seneca, New York, United States
United States, Ohio
Sp1004 002
Cincinnati, Ohio, United States
United States, Pennsylvania
Sp1004 016
West Chester, Pennsylvania, United States
United States, Texas
Sp1004 003
Austin, Texas, United States
Sponsors and Collaborators
UCB BIOSCIENCES, Inc.
Investigators
Study Director: UCB Clinical Trial Call Center 1-877-822-9493 (UCB)
  More Information

No publications provided

Responsible Party: UCB Pharma ( UCB BIOSCIENCES, Inc. )
ClinicalTrials.gov Identifier: NCT01495793     History of Changes
Other Study ID Numbers: SP1004, 2014-004383-37
Study First Received: December 16, 2011
Results First Received: April 29, 2015
Last Updated: June 17, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by UCB Pharma:
Rotigotine
Restless Legs Syndrome
RLS
Children
Adolescents

Additional relevant MeSH terms:
Psychomotor Agitation
Restless Legs Syndrome
Syndrome
Disease
Dyskinesias
Dyssomnias
Mental Disorders
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Parasomnias
Pathologic Processes
Psychomotor Disorders
Signs and Symptoms
Sleep Disorders
Sleep Disorders, Intrinsic
N 0437
Dopamine Agents
Dopamine Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 30, 2015