Study to Evaluate the Efficacy of Rotigotine on Parkinson's Disease-Associated Pain (DOLORES)

A Multicenter, Multinational, Double-Blind, Placebo-Controlled, 2-Arm Study to Evaluate the Efficacy of Rotigotine on Parkinson's Disease-Associated Pain

This trial is being conducted to compare the impact of Rotigotine and Placebo on Chronic Pain associated with Parkinson's Disease among patients with advanced stages of the disease.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Gera, Germany
    • 1204
• Poland
  • Gdansk, Poland
    • 1607
  • Krakow, Poland
    • 1603
  • Olsztyn, Poland
    • 1609
• Slovakia
  • Bratislava, Slovakia
    • 1804
  • Dubnica Nad Vahom, Slovakia
    • 1805
• United States
  • Arizona
    • Gilbert, Arizona, United States
      • 2113
  • California
    • Sunnyvale, California, United States
      • 2120
  • Florida
    • Tampa, Florida, United States
      • 2109
  • Illinois
    • Chicago, Illinois, United States
      • 2107
  • Kentucky
    • Lexington, Kentucky, United States
      • 2102
  • North Carolina
    • Advance, North Carolina, United States
      • 2118
  • Ohio
    • Cincinnati, Ohio, United States
      • 2117
  • Oklahoma
    • Tulsa, Oklahoma, United States
      • 2103
  • Virginia
    • Roanoke, Virginia, United States
      • 2101
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • 2104

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient has advanced idiopathic Parkinson's Disease associated chronic pain assessed by a Likert Pain Scale
• Patient is taking Levodopa with a stable daily dose of at least 200 mg for at least 21 days prior to start
• Hoehn and Yahr stage score of II to IV
• Mini-Mental State Examination (MMSE) score ≥ 25
• If an antidepressant drug is taken, the dose must be stable for at least 21 days

Exclusion Criteria:

• Therapy with a Dopamine Agonist within 21 days prior to start
• Discontinuation from previous Dopamine Agonist Therapy due to lack of efficacy
• Therapy with Dopamine-modulating substances 21 days prior to start
• Therapy with analgesics for the treatment for pain, unless the dose has been stable
• Chronic alcohol or drug abuse
• Medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the patient's ability to participate in this study
• Hypersensitivity to any components of the Investigational Medicinal Product (IMP) or comparative drugs
• Atypical Parkinson's Disease Syndrome due to drugs
• History of deep brain stimulation
• Significant skin disease that would make transdermal drug use inappropriate
• Electroconvulsive therapy within 12 weeks prior to start
• Evidence of an Impulse Control Disorder
• Previous diagnosis of severe Restless Legs Syndrome
• Chronic Migraine
• Severe Depression
• Symptomatic Orthostatic Hypotension

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo Transdermal Patches	Drug: Placebo; Placebo patches match the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and will contain Placebo. Application of Placebo patches starts at the Baseline Visit. Placebo patches will be administered once daily starting with the equivalent of 4 mg / 24 h. Doses will then be up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose is reached. The maximum dose is the equivalent to 16 mg / 24 h. The duration of the Titration Period will vary from 1 to 7 weeks. The Maintenance Period will last 12 weeks ± 5 days. During the De-escalation Period, the dose of Placebo will be decreased by the equivalent to 2 mg / 24 h every other day. The De-escalation Period may last up to 12 days.
Experimental: Rotigotine; Rotigotine Transdermal Patches	Drug: Rotigotine; Patches will contain 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication starts at the Baseline Visit. Rotigotine will be administered once daily starting at 4 mg / 24 h. Doses will then be up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) is reached and the Maintenance Period can be started. The duration of the Titration Period will vary from 1 to 7 weeks ± 3 days. The Maintenance Period will last 12 weeks ± 5 days. Thereafter, during the De-escalation Period, the dose of study medication will be decreased by 2 mg / 24 h every other day. The De-escalation Period may last up to 12 days.; Other Names: (6S)-6-propyl-[2 (2 thienyl)ethyl]amino-5,6,7,8-tetrahydro-1-naphthalenol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to the End of the Maintenance Period in Pain Severity Assessed Using an 11-point Likert Pain Scale	An 11-Point Likert Scale was used to assess patients' average daily pain. The subject rated his/her average pain from 0 (no pain) to 10 (worst pain ever experienced). The average pain experienced in the last 7 days was calculated by the mean of the daily Likert Pain Scores within the 7 days prior to the respective visit (ie, Likert Pain Scores with a date of assessment before the date of visit and on or after the date of visit - 7 days). A negative value indicates an improvement.	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after an up to 7 weeks Titration Period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders at the End of the Maintenance Period	Responders are defined as patients experiencing a 2-Point or more Reduction on an 11-Point Likert Pain Scale from Baseline to the End of the Maintenance Period. An 11-Point Likert Scale was used to assess patients' average daily pain. The patient rated his/her average pain from 0 (no pain) to 10 (worst pain ever experienced).	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)
Change From Baseline to the End of the Maintenance Period in the Sum Score of the 8-Item Parkinson's Disease Questionnaire (PDQ-8)	The 8-Item Parkinson's Disease Questionnaire (PDQ-8) (Peto et al, 1998) is a self-administered questionnaire that provides a reliable measure of overall health status. The PDQ-8 contains 8 items of daily living, with 1 item selected from each of the following 8 scales: mobility, Activities of Daily Living (ADL), emotional well being, stigma, social support, cognitions, communication, and bodily discomfort. The total PDQ-8 score is the sum of all the individual items converted to a summary index score between 0 and 100, with lower scores indicating better health. A negative value indicates an improvement.	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)
Change From Baseline to the End of the Maintenance Period in the 7-Item Depression Subscore of the Hospital Anxiety and Depression Scale (HADS)	The Hospital Anxiety and Depression Scale (HADS) (Zigmond and Snaith, 1983) is a 14-item self-assessment scale for detecting states of depression and anxiety in the setting of a hospital medical outpatient clinic. It comprises a 7-item anxiety subscale and a 7-item depressive subscale that are also measures of severity of the emotional disorder. The 14 items are scored between 0 and 3. The 7-item depression subscore and 7-item anxiety subscore were calculated as the sum of the 7 corresponding individual scores. A negative value indicates an improvement.	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)
Change From Baseline to the End of the Maintenance Period in the 7-Item Anxiety Subscore of the Hospital Anxiety and Depression Scale (HADS)	The Hospital Anxiety and Depression Scale (HADS) (Zigmond and Snaith, 1983) is a 14-item self-assessment scale for detecting states of depression and anxiety in the setting of a hospital medical outpatient clinic. It comprises a 7-item anxiety subscale and a 7-item depressive subscale that are also measures of severity of the emotional disorder. The 14 items are scored between 0 and 3. The 7-item depression subscore and 7-item anxiety subscore were calculated as the sum of the 7 corresponding individual scores. A negative value indicates an improvement.	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)
Change From Baseline to the End of the Maintenance Period in the Combined Score of the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II (Activities of Daily Living [ADL] Subscale) and III (Motor Subscale)	Part II of the Unified Parkinson's Disease Rating Scale (UPDRS) assesses the subject's activities of daily living. Part III assesses motor function. The UPDRS is completed by questioning the subject about his/her general state in conjunction with any observations made by the investigator (or designee) since the previous visit. Part II is subject-rated and Part III is physician-rated. The UPDRS Part II (Activities of Daily Living) consists of 13 items scored between 0 and 4. The sum score was calculated as the sum of these 13 individual scores. The UPDRS Part III (motor subscale) consists of 27 items and sub items scored between 0 and 4. The sum score was calculated as sum of these 27 individual scores. The sum score of UPDRS Parts II and III is the sum of the corresponding single sum scores. A negative value indicates an improvement.	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)
Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease	The classification of pain in Parkinson's disease scale classifies pain in the following domains: musculoskeletal pain (item 1), chronic pain (items 2 and 3), fluctuation related pain (items 4, 5 and 6), nocturnal pain (items 7 and 8), oro-facial pain (items 9, 10 and 11), discoloration; edema/swelling (items 12 and 13), and radicular pain (item 14). Severity of the pain is measured on a scale from none (0) to severe (3) and frequency is measured on a scale from never (0) to very frequent (4). A score of a single item was calculated by multiplying severity with frequency. A domain score was calculated as the sum of every individual score related to the respective domain. A negative value indicates an improvement.	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES GmbH

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: December 5, 2012
• First Submitted That Met QC Criteria: December 5, 2012
• First Posted (Estimate): December 6, 2012

Study Record Updates

• Last Update Posted (Estimate): May 1, 2015
• Last Update Submitted That Met QC Criteria: April 9, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Chronic Pain; Parkinson's Disease; Rotigotine; Nonmotor symptoms
• 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: PD0004; 2012-002608-42 (EudraCT Number)