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

NCT01495793 | Completed Phase 2 Results

• 2 other identifiers: SP10042014-004383-37
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 12

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).

Conditions

Restless Legs Syndrome

Keywords

Rotigotine; Restless Legs Syndrome; RLS; Children; Adolescents

Outcome Measures

Primary Outcomes (8)

• Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 0.5 mg/24 h (2.5 cm^2)

  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.

  0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

• Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 1 mg/24 h (5 cm^2)

  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.

  0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

• Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 2 mg/24 h (10 cm^2)

  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.

  0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

• Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 3 mg/24 h (15 cm^2)

  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.

  0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

• Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 0.5 mg/24 h (2.5 cm^2)

  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.

  0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

• Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 1 mg/24 h (5 cm^2)

  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.

  0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

• Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 2 mg/24 h (10 cm^2)

  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.

  0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

• Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 3 mg/24 h (15 cm^2)

  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.

  0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

Study Arms (1)

Rotigotine

EXPERIMENTAL

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

Interventions

Rotigotine DRUG

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.

Rotigotine

Eligibility Criteria

• Age: 13 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB BIOSCIENCES, Inc.: lead

Study Sites (12)

Sp1004 006

Little Rock, Arkansas, United States

Location

Sp1004 012

Los Angeles, California, United States

Location

Sp1004 009

Orange, California, United States

Location

Sp1004 005

Washington D.C., District of Columbia, United States

Location

Sp1004 014

Spring Hill, Florida, United States

Location

Sp1004 013

Indianapolis, Indiana, United States

Location

Sp1004 001

Destrehan, Louisiana, United States

Location

Sp1004 015

St Louis, Missouri, United States

Location

Sp1004 007

West Seneca, New York, United States

Location

Sp1004 002

Cincinnati, Ohio, United States

Location

Sp1004 016

West Chester, Pennsylvania, United States

Location

Sp1004 003

Austin, Texas, United States

Location

Related Publications (1)

• 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.

  PMID: 28366342 RESULT

MeSH Terms

Conditions

Restless Legs Syndrome

Interventions

rotigotine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Results Point of Contact

• Title: UCB Clinical Trial Call Center
• Organization: UCB Pharma

+1877-822

Study Officials

• UCB Clinical Trial Call Center

  1-877-822-9493 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2011
• First Posted: December 20, 2011
• Study Start: December 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: April 4, 2018
• Results First Posted: July 14, 2015

Record last verified: 2018-03

Locations

US (12)