A Sleep Laboratory Study to Investigate the Safety and Efficacy of the Rotigotine Skin Patch in Subjects With Restless Legs Syndrome and End-Stage Renal Disease Requiring Hemodialysis

NCT01537042 | Completed Phase 3 Results

• 2 other identifiers: SP09342011-003486-15
• Study Type: interventional
• Target: 30
• Locations: 6 countries
• Sites: 15

Brief Summary

This is a sleep laboratory study to evaluate the efficacy and safety of Rotigotine in subjects with Restless Legs Syndrome and End-Stage Renal Disease requiring hemodialysis. The objectives are to demonstrate superiority of Rotigotine against Placebo as well as to investigate the effect of Rotigotine on quality of life and sleep.

Conditions

Restless Legs Syndrome; End-Stage Renal Disease

Keywords

Rotigotine; Neupro; Restless Legs Syndrome; RLS; End-Stage Renal Disease

Outcome Measures

Primary Outcomes (1)

• Ratio From Baseline to the End of the 2-week Maintenance Period in Periodic Limb Movement Index (PLMI)

  The PLMI is defined as Periodic Limb Movements (PLMs)/ total time in bed in hours. PLMs are measured by Polysomnography (PSG). The reduction of the PLMI is reflected in terms of the ratio from Baseline to the end of the Maintenance Period and was calculated as \[PLMI at end of Maintenance Period (MP)\] / \[PLMI at Baseline\]. A PLMI Ratio \<1 indicates an improvement from Baseline to the end of the 2-week MP.

  From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Secondary Outcomes (14)

• Change From Baseline in the Periodic Limb Movements Index (PLMI) to the End of the Maintenance Period

  From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

• Change From Baseline in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) Sum Score to the End of the Maintenance Period

  From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

• Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score

  Visit 2 (Baseline); Visit 6 (End of Maintence Period)

• Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 1 to the End of the Maintenance Period

  From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

• Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 2 to the End of the Maintenance Period

  From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Study Arms (2)

Rotigotine

EXPERIMENTAL

Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.

Drug: Rotigotine

Placebo

PLACEBO COMPARATOR

Transdermal patch matched according to patch size and appearance.

Drug: Placebo

Interventions

Rotigotine DRUG

Transdermal patch; Dose: 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h. Subjects start with a Rotigotine dose of 1 mg/24 h for 1 week. The dose can be increased weekly during Up-Titration Period until either the optimal or the maximal dose of 3 mg/24 h has been reached. Subjects will maintain the optimal/maximal dose during the 2-week Maintenance Period. Following the Maintenance Period, subjects will be de-escalated from their optimal dose by decreasing the dose by 1 mg/24 h every other day during Taper Period until complete withdrawal.

Also known as: Neupro

Rotigotine

Placebo DRUG

Transdermal patch; Patches matching to active treatment patches in size and appearance. Up to 3 weeks of Titration, 2 weeks of Maintenance, Up to 4 days of Taper Period.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• End-Stage Renal Disease (ESRD) requiring hemodialysis and regular dialysis schedule
• Fulfillment of pre-defined criteria of hematology parameters
• Diagnosis of Restless Legs (RLS) based on the 4 cardinal diagnostic clinical features according to the International Restless Legs Syndrome Study Group
• Initial response to previous dopaminergic treatment for RLS, or has had no previous dopaminergic treatment (ie, de novo)
• Score of ≥ 15 points on the IRLS (indicating moderate to severe RLS) at Baseline
• Score of ≥ 11 points on the RLS-DI (Diagnostic Index) at Baseline
• Score of ≥ 4 points on the Clinical Global Impressions (CGI) Item 1 assessment (indicating moderately ill) at Baseline
• Scores ≥ 15 Periodic Limb Movements (PLMs) per hour on the Periodic Limb Movement Index (PLMI) based on Polysomnography (PSG) (recorded during the second night) as assessed by the investigator at Baseline

You may not qualify if:

• Clinically relevant Polyneuropathy or Varicosis which cannot be clearly differentiated from RLS symptoms in the opinion of the investigator
• Clinically relevant concomitant diseases, such as Attention Deficit Hyperactivity Disorder, Painful Legs, and Moving Toes
• Other central nervous system diseases
• Evidence of an impulse control disorder according to the modified Minnesota Impulsive Disorders Interview (mMIDI)
• Lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('yes') to either Question 4 or Question 5 of the Columbia-Suicidality Severity Rating Scale (C-SSRS) at Screening (Visit 1) or Baseline (Visit 2)
• Prior history of psychotic episodes
• History of symptomatic (not asymptomatic) Orthostatic Hypotension
• Clinically relevant Cardiovascular Disease
• Clinically relevant Venous or Arterial Peripheral Vascular Disease
• Malignant Neoplastic Disease requiring therapy within 12 months prior to Screening (Visit 1)
• Treatment with any of the following drug classes: neuroleptics, norepinephrine and dopamine reuptake inhibitors (bupropion), gabapentin, budipine, dopamine antagonist antiemetics (except domperidone), opioids, monoamine oxidase (MAO) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, or psychostimulants (eg, amphetamines)
• Subject is pregnant, nursing, or is a woman of childbearing potential who is not surgically sterile, 2 years postmenopausal, or does not consistently use 2 combined effective methods of contraception (including at least 1 barrier method), unless sexually abstinent
• Previous treatment with dopamine agonists within a period of 14 days prior to Baseline (Visit 2), or L-dopa within 7 days prior to Baseline (Visit 2)
• Medical history indicating intolerability to dopaminergic therapy (if pretreated) or has experienced Augmentation (Garcia-Borreguero and Williams, 2010) when previously treated with any dopaminergic agent
• Subject has received previous treatment with Rotigotine

Sponsors & Collaborators

• UCB BIOSCIENCES GmbH: lead

Study Sites (15)

606

Brandon, Florida, United States

Location

604

Newton, Massachusetts, United States

Location

603

West Seneca, New York, United States

Location

607

Dublin, Ohio, United States

Location

605

West Chester, Pennsylvania, United States

Location

601

Austin, Texas, United States

Location

101

Innsbruck, Austria

Location

201

Helsinki, Finland

Location

203

Tampere, Finland

Location

302

Bordeaux, France

Location

301

Montpellier Cédex 5, France

Location

404

Berlin, Germany

Location

401

Marburg, Germany

Location

402

Schwerin, Germany

Location

502

Pisa, Italy

Location

MeSH Terms

Conditions

Restless Legs Syndrome; Kidney Failure, Chronic

Interventions

rotigotine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: UCB Clinical Trial Call Center

+1 887 822 9493

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2012
• First Posted: February 22, 2012
• Study Start: April 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 3, 2014
• Results First Posted: November 3, 2014

Record last verified: 2014-10

Locations

AU (1); FI (2); DE (3); FR (2); IT (1); US (6)