Placebo-controlled Study in Patients With Parkinson's Disease to Evaluate the Effect of Rotigotine on Non-motor Symptoms

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc.
ClinicalTrials.gov Identifier:
NCT01300819
First received: February 18, 2011
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

The primary objective of this study was to demonstrate that Rotigotine improves non-motor symptoms compared to Placebo in subjects with Parkinson's Disease.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multicenter, Double-blind, Placebo-controlled, Parallel-group, Phase IV Study to Assess the Effect of Rotigotine on Non-motor Symptoms in Patients With Idiopathic Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

Primary Outcome Measures:
  • Change From Baseline to the End of Maintenance in Total Nonmotor Symptoms Scale (NMSS) Score [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]
    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in the following 9 domain categories: cardiovascular, including falls; sleep/fatigue; mood/cognition; perceptual problems/hallucinations; attention/memory; gastrointestinal tract; urinary; sexual function; miscellaneous. Severity and frequency are rated using a 4-point scale ranging from 0 (none) to 3 (severe; major source of distress or disturbance to subject) for severity and from 1 (rarely) to 4 (very frequent [daily or all the time]) for frequency. The total NMSS score ranges from 0 to 350. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.


Secondary Outcome Measures:
  • Change From Baseline to the End of Maintenance in Total Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]
    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 from Baseline to end of Maintenance score indicates improvement.

  • Change From Baseline to the End of Maintenance in Health-related Quality of Life (HRQL) Measured by a 39-item Parkinson's Disease Questionnaire (PDQ-39) [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]
    Parkinson's Disease Questionnaire - 39 (PDQ-39) is a self-administered questionnaire. It comprises of 39 questions, relating to eight key areas of health and daily activities, including both Motor and Non-motor symptoms. It is scored on a scale of zero to 100, with lower scores indicating better health and high scores more severe symptoms in change from Baseline to end of Maintenance.

  • Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Cardiovascular [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]

    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.

    The final score is derived from multiplying the severity score and the frequency score.

    A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.

    The possible min/max final scores per subdomain are calculated as follows:

    Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain:

    Subdomain Cardiovascular (2 questions): range 0 - 24


  • Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sleep/Fatigue [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]

    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.

    The final score is derived from multiplying the severity score and the frequency score.

    A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.

    The possible min/max final scores per subdomain are calculated as follows:

    Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain:

    Subdomain Sleep/Fatigue (4 questions): range 0-48


  • Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Mood/Cognition [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]

    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.

    The final score is derived from multiplying the severity score and the frequency score.

    A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.

    The possible min/max final scores per subdomain are calculated as follows:

    Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain:

    Subdomain Mood/Cognition (6 questions): range 0 - 72


  • Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Perception/Hallucinations [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]

    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.

    The final score is derived from multiplying the severity score and the frequency score.

    A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.

    The possible min/max final scores per subdomain are calculated as follows:

    Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain:

    Subdomain Perception/Hallucinations (3 questions): range 0 - 36


  • Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Attention/Memory, [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]

    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.

    The final score is derived from multiplying the severity score and the frequency score.

    A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.

    The possible min/max final scores per subdomain are calculated as follows:

    Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain:

    Subdomain Attention/Memory (3 questions): range 0 - 36


  • Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Gastrointestinal Tract [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]

    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.

    The final score is derived from multiplying the severity score and the frequency score.

    A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.

    The possible min/max final scores per subdomain are calculated as follows:

    Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain:

    Subdomain Gastrointestinal tract (3 questions): range 0 - 36


  • Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Urinary [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]

    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.

    The final score is derived from multiplying the severity score and the frequency score.

    A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.

    The possible min/max final scores per subdomain are calculated as follows:

    Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain:

    Subdomain Urinary (3 questions): range 0 - 36


  • Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sexual Function [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]

    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.

    The final score is derived from multiplying the severity score and the frequency score.

    A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.

    The possible min/max final scores per subdomain are calculated as follows:

    Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain:

    Subdomain Sexual function (2 questions): range 0 - 24


  • Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Miscellaneous [ Time Frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84) ] [ Designated as safety issue: No ]

    The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.

    The final score is derived from multiplying the severity score and the frequency score.

    A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.

    The possible min/max final scores per subdomain are calculated as follows:

    Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain:

    Subdomain Miscellaneous (4 questions): range 0 - 48



Enrollment: 349
Study Start Date: February 2011
Study Completion Date: November 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Other: Placebo

Placebo patches of 2, 4, 6 & 8 mg / 24 hours Daily application of Placebo patches starting at 2 mg / 24 hours (early Parkinson's Disease (PD) patients) or 4 mg / 24 hours (advanced PD patients). Dose was up-titrated in weekly increments of 2 mg / 24 hours until optimal or maximal dose was reached. Maximal dose was 8 mg / 24 hours for early PD patients and 16 mg / 24 hours for advanced PD patients.

Optimal or maximal dose was maintained for 12 weeks followed by a de-escalation by 2 mg / 24 hours every other day.

Experimental: Rotigotine Drug: Rotigotine

Rotigotine patches of 2, 4, 6, and 8 mg / 24 hours

Once daily application of Rotigotine patches starting at 2 mg / 24 hours (early Parkinson's Disease (PD) patients) or 4 mg / 24 hours (advanced PD patients). Dose was up-titrated in weekly increments of 2 mg / 24 hours until optimal or maximal dose was reached. Maximal dose is 8 mg / 24 hours for early PD patients and 16 mg / 24 hours for advanced PD patients.

Optimal or maximal dose was maintained for 12 weeks followed by a de-escalation by 2 mg / 24 hours every other day.

Other Name: Neupro®

  Eligibility

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

Inclusion Criteria:

  • Subject is male or female, ≥18 years of age
  • Subject has idiopathic Parkinson's disease with at least 2 of the following cardinal signs being present: bradykinesia, resting tremor, rigidity or postural instability, and without any other known or suspected cause of Parkinsonism
  • Subject has a Hoehn and Yahr stage score ≤4
  • Subject has a total Non-Motor Symptoms Scale (NMSS) score ≥40
  • If the subject is taking levodopa (L-DOPA), he/she must be on a stable dose of L-DOPA (in combination with benserazide or carbidopa) for at least 28 days prior to the Baseline Visit
  • If the subject is receiving anticholinergics, monoamine oxidase (MAO) B inhibitors, or amantadine, he/she must have been on a stable dose for at least 28 days prior to the Baseline Visit and must be maintained on that dose for the duration of the study

Exclusion Criteria:

  • Subject discontinued from previous therapy with a dopamine agonist after an adequate length of treatment, at an adequate dose, due to lack of efficacy as assessed by the investigator
  • Subject is receiving therapy with 1 of the following drugs, either concurrently or within 28 days prior to the Baseline Visit: alpha-methyl dopa, metoclopramide, reserpine, neuroleptics (except specific atypical neuroleptics: olanzapine, ziprasidone, aripiprazole, clozapine, and quetiapine), monoamine oxidase-A (MAO-A) inhibitors, methylphenidate, amphetamine, or other dopamine agonists (DAs)
  • Subject is receiving central nervous system (CNS) therapy (eg, sedatives, hypnotics, selective serotonin reuptake inhibitors [SSRIs], anxiolytics, or other sleep-modifying medication) unless dose has been stable daily for at least 28 days prior to the Baseline Visit and is likely to remain stable for the duration of the study
  • Subject has evidence of an impulse control disorder according to the modified Minnesota Impulsive Disorders Interview at the Screening Visit (Visit 1), confirmed by a positive structured clinical interview
  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: NCT01300819

  Show 87 Study Locations
Sponsors and Collaborators
UCB, Inc.
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Additional Information:
No publications provided

Responsible Party: UCB, Inc.
ClinicalTrials.gov Identifier: NCT01300819     History of Changes
Other Study ID Numbers: SP0976, 2010-021394-37
Study First Received: February 18, 2011
Results First Received: October 25, 2013
Last Updated: April 9, 2014
Health Authority: Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Romania: National Medicines Agency
Slovakia: State Institute for Drug Control
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic

Keywords provided by UCB, Inc.:
Rotigotine
Neupro®
Non-motor symptoms

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
N 0437
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2014