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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier:
NCT01744496
First received: December 5, 2012
Last updated: April 9, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Advanced Idiopathic Parkinson's Disease
Drug: Rotigotine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Multinational, Double-Blind, Placebo-Controlled, 2-Arm Study to Evaluate the Efficacy of Rotigotine on Parkinson's Disease-Associated Pain

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • Change From Baseline to the End of the Maintenance Period in Pain Severity Assessed Using an 11-point Likert Pain Scale [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after an up to 7 weeks Titration Period) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Percentage of Responders at the End of the Maintenance Period [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period) ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline to the End of the Maintenance Period in the Sum Score of the 8-Item Parkinson's Disease Questionnaire (PDQ-8) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to the End of the Maintenance Period in the 7-Item Depression Subscore of the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to the End of the Maintenance Period in the 7-Item Anxiety Subscore of the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period) ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period) ] [ Designated as safety issue: No ]

    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.



Enrollment: 68
Study Start Date: November 2012
Study Completion Date: January 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: (6S)-6-propyl-[2 (2 thienyl)ethyl]amino-5,6,7,8-tetrahydro-1-naphthalenol
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01744496

Locations
United States, Arizona
2113
Gilbert, Arizona, United States
United States, California
2120
Sunnyvale, California, United States
United States, Florida
2109
Tampa, Florida, United States
United States, Illinois
2107
Chicago, Illinois, United States
United States, Kentucky
2102
Lexington, Kentucky, United States
United States, North Carolina
2118
Advance, North Carolina, United States
United States, Ohio
2117
Cincinnati, Ohio, United States
United States, Oklahoma
2103
Tulsa, Oklahoma, United States
United States, Virginia
2101
Roanoke, Virginia, United States
United States, Wisconsin
2104
Milwaukee, Wisconsin, United States
Germany
1204
Gera, Germany
Poland
1607
Gdansk, Poland
1603
Krakow, Poland
1609
Olsztyn, Poland
Slovakia
1804
Bratislava, Slovakia
1805
Dubnica Nad Vahom, Slovakia
Sponsors and Collaborators
UCB BIOSCIENCES GmbH
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Additional Information:
No publications provided

Responsible Party: UCB Pharma ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier: NCT01744496     History of Changes
Other Study ID Numbers: PD0004, 2012-002608-42
Study First Received: December 5, 2012
Results First Received: November 24, 2014
Last Updated: April 9, 2015
Health Authority: Argentina: Ministry of Health
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Hungary: National Institute of Pharmacy
Mexico: Federal Commission for Protection Against Health Risks
Poland: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
Ukraine: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by UCB Pharma:
Parkinson's Disease
Rotigotine
Chronic Pain
Nonmotor symptoms

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders
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 May 05, 2015