Trial to Assess Parkinson's Disease (PD) Symptom Control to Four Doses of Rotigotine in a Transdermal Patch

A Multicenter, Randomized, Double-blind, Placebo-controlled, 5-arm, Parallel-group Trial to Assess Rotigotine Transdermal System Dose Response in Subjects With Advanced-stage Parkinson's Disease

The purpose of this study is to show Rotigotine dose response at four doses of Rotigotine used with L-dopa in treating advanced stage Parkinson's disease.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Rotigotine; Drug: Rotigotine; Drug: Rotigotine; Drug: Rotigotine; Other: Placebo

Detailed Description

To maintain treatment blind, two different active patch sizes were used (10 cm^2 & 20 cm^2). Placebo patches matched according to size and appearance. During the trial subjects applied up to three patches, active and placebo, to achieve their assigned daily dose.

• Study Type: Interventional
• Enrollment (Actual): 514
• Phase: Phase 3

Contacts and Locations

Study Locations

• Chile
  • Santiago de Chile, Chile
• India
  • Andhra Pradesh
    • Hyderbad, Andhra Pradesh, India
  • Kamataka
    • Bangalore, Kamataka, India
    • Mangalore, Kamataka, India
  • Karnataka
    • Mysore, Karnataka, India
  • Kerala
    • Calicut, Kerala, India
    • Thiruvananthapuram, Kerala, India
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India
  • Maharashtra
    • Mumbai, Maharashtra, India
    • Pune, Maharashtra, India
  • Tamil Nadu
    • Chennai, Tamil Nadu, India
• Mexico
  • Aguascalientes, Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico
• Peru
  • Lima
    • San Isidro, Lima, Peru
    • Santiago de Surco, Lima, Peru
• United States
  • Alabama
    • Birmingham, Alabama, United States
    • Tuscaloosa, Alabama, United States
  • Arizona
    • Gilbert, Arizona, United States
    • Peoria, Arizona, United States
    • Phoenix, Arizona, United States
    • Scottsdale, Arizona, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Fountain Valley, California, United States
    • Fresno, California, United States
    • Irvine, California, United States
    • La Jolla, California, United States
    • Loma Linda, California, United States
    • Oxnard, California, United States
  • Colorado
    • Aurora, Colorado, United States
  • Connecticut
    • New Haven, Connecticut, United States
  • Florida
    • Boca Raton, Florida, United States
    • Bradenton, Florida, United States
    • Jacksonville, Florida, United States
    • Miami, Florida, United States
    • Naples, Florida, United States
    • Ocala, Florida, United States
    • Ormond Beach, Florida, United States
    • Pompano Beach, Florida, United States
    • St. Petersburg, Florida, United States
    • Sunrise, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Decatur, Georgia, United States
    • Macon, Georgia, United States
    • Suwanee, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Indiana
    • Anderson, Indiana, United States
  • Iowa
    • Des Moines, Iowa, United States
  • Kansas
    • Kansas City, Kansas, United States
  • Kentucky
    • Louisville, Kentucky, United States
  • Michigan
    • Southfield, Michigan, United States
  • Minnesota
    • Golden Valley, Minnesota, United States
  • Missouri
    • St Louis, Missouri, United States
  • Montana
    • Missoula, Montana, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New York
    • Commack, New York, United States
    • New York, New York, United States
    • Rochester, New York, United States
  • North Carolina
    • Raleigh, North Carolina, United States
    • Salisbury, North Carolina, United States
  • Ohio
    • Columbus, Ohio, United States
    • Toledo, Ohio, United States
  • Pennsylvania
    • Greensburg, Pennsylvania, United States
    • Souderton, Pennsylvania, United States
    • Upland, Pennsylvania, United States
  • Tennessee
    • Memphis, Tennessee, United States
  • Texas
    • Lubbock, Texas, United States
    • San Antonio, Texas, United States
  • Utah
    • Midvale, Utah, United States
    • South Ogden, Utah, United States
  • Virginia
    • Alexandria, Virginia, United States
    • Richmond, Virginia, United States
    • Roanoke, Virginia, United States
    • Virginia Beach, Virginia, United States
  • Washington
    • Kirkland, Washington, United States
    • Spokane, Washington, United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• PD greater than 3 years
• Stable dose L-dopa but symptoms not adequately controlled and have "off" time
• Able and willing to complete diary on specific days

Exclusion Criteria:

• Previous use of rotigotine or Neupro
• Atypical Parkinson's syndrome
• Pallidotomy
• Thalamotomy
• Deep brain stimulation
• Fetal tissue transplant
• Dementia
• Psychosis
• Hallucinations
• Epilepsy
• Renal or hepatic dysfunction
• Clinically relevant cardiac dysfunction
• Symptomatic orthostatic hypotension
• Skin sensitivity to adhesives or unresolved contact dermatitis
• History of chronic alcohol or drug abuse
• Pregnant or of child-bearing potential
• Impulse control disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo transdermal patch applied daily
Experimental: Rotigotine 2 mg/24 hr	Drug: Rotigotine; 2 mg/24 hr (one 10 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 4 mg/24 hr (one 20 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 6 mg/24 hr (one 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 8 mg/24 hr (two 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro
Experimental: Rotigotine 4 mg/24 hr	Drug: Rotigotine; 2 mg/24 hr (one 10 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 4 mg/24 hr (one 20 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 6 mg/24 hr (one 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 8 mg/24 hr (two 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro
Experimental: Rotigotine 6 mg/24 hr	Drug: Rotigotine; 2 mg/24 hr (one 10 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 4 mg/24 hr (one 20 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 6 mg/24 hr (one 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 8 mg/24 hr (two 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro
Experimental: Rotigotine 8 mg/24 hr	Drug: Rotigotine; 2 mg/24 hr (one 10 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 4 mg/24 hr (one 20 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 6 mg/24 hr (one 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro; Drug: Rotigotine; 8 mg/24 hr (two 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks; Other Names: Neupro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change in the Absolute Time Spent "Off" From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary	Time "Off" is defined as when the patient does not have the effect of anti-Parkinson's medication.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change in Relative Time Spent "Off" From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary	Time "Off" is defined as when the patient does not have the effect of anti-Parkinson's medication.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Absolute Time Spent "on" From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary	Time "On" is defined as when the patient has the effect of anti-Parkinson's medication.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Relative Time Spent "on" From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary	Time "On" is defined as when the patient has the effect of anti-Parkinson's medication.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Status of the Subject After Wake-Up From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary		From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II From Baseline to the End of the Maintenance Period	The Unified Parkinson's Disease Rating Scale (UPDRS) Part II is a scale for the assessment of function in Parkinson's disease. UPDRS Part II measures Activities of Daily Living. It consists of 13 questions, each ranging from 0 to 4. The sum score of the UPDRS Part II ranges from 0 to 52. A higher score indicates greater disability. A negative change score indicates improvement.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III From Baseline to the End of the Maintenance Period	The Unified Parkinson's Disease Rating Scale (UPDRS) Part III is a scale for the assessment of function in Parkinson's disease. UPDRS Part III measures Motor Function. It consists of 14 items with 27 questions, each ranging from 0 to 4. The sum score for the UPDRS Part III ranges from 0 to 108. A higher score indicates greater disability. A negative change score indicates improvement.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - What Proportion of the Waking Day Are Dyskinesias Present?	Item = Duration (question #32) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period - What proportion of the waking day are dyskinesias present? Has a possible score of 0 - 4 points (4 = maximum). A higher score indicates more severe symptoms. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Disability: How Disabling Are the Dyskinesias?	Item = Disability (question #33) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period - How disabling are the dyskinesias? Has a possible score of 0 - 4 points (4 = maximum). A higher score indicates more severe symptoms. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Painful Dyskinesias: How Painful Are the Dyskinesias?	Item = Painful Dyskinesia (question #34) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period - How painful are the dyskinesias? Has a possible score of 0 - 4 points (4 = maximum). A higher score indicates more severe symptoms. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Presence of Early Morning Dystonia	Item = Presence of Early Morning Dystonia (question #35) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates early morning dystonia. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Are "Off" Periods Predictable?	Item = Are "off" periods predictable (question #36) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates "off" periods are predictable. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Are "Off" Periods Unpredictable?	Item = Are "off" periods unpredictable (question #37) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates "off" periods are unpredictable. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Do "Off" Periods Come on Suddenly?	Item = Do "off" periods come on suddenly, within a few seconds (question #38) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates "off" periods come on suddenly, within a few seconds. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - What Proportion of the Waking Day is the Subject "Off", on Average?	Item = What proportion of the waking day is the subject "off", on average (question #39) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 - 4 points (4 = maximum). A higher score indicates the subject is "off" a larger portion of the waking day. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Does the Patient Have Anorexia, Nausea, or Vomiting?	Item = Does the patient have anorexia, nausea, or vomiting (question #40) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates subject has anorexia, nausea, or vomiting. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Does the Patient Have Any Sleep Disturbances Such as Insomnia or Hypersomnolence?	Item = Does the patient have any sleep disturbances such as insomnia or hypersomnolence (question #41) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates subject has sleep disturbances such as insomnia or hypersomnolence. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Does the Patient Have Symptomatic Orthostasis?	Item = Does the patient have symptomatic orthostasis (question #42) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates subject has symptomatic orthostasis. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].
The Change in Number of "Off" Periods From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary	Time "Off" is defined as when the patient does not have the effect of anti-Parkinson's medication.	From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)].

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

General Publications

• LeWitt PA, Poewe W, Elmer LW, Asgharnejad M, Boroojerdi B, Grieger F, Bauer L. The Efficacy Profile of Rotigotine During the Waking Hours in Patients With Advanced Parkinson's Disease: A Post Hoc Analysis. Clin Neuropharmacol. 2016 Mar-Apr;39(2):88-93. doi: 10.1097/WNF.0000000000000133.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: August 28, 2007
• First Submitted That Met QC Criteria: August 28, 2007
• First Posted (Estimate): August 29, 2007

Study Record Updates

• Last Update Posted (Estimate): October 27, 2014
• Last Update Submitted That Met QC Criteria: October 17, 2014
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: transdermal; patch; Neupro; Parkinson's disease; rotigotine; dopamine agonist; off time
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Rotigotine
• Other Study ID Numbers: SP0921

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No