Trial to Evaluate The Efficacy Of Rotigotine on Parkinson's Disease-Associated Motor Symptoms And Apathy (BRIGHT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier:
NCT01782222
First received: January 30, 2013
Last updated: January 16, 2015
Last verified: January 2015
  Purpose

This trial is being conducted to assess the effects of Rotigotine over Placebo on improvement of Apathy and motor symptoms in subjects with early-stage and advanced stage idiopathic Parkinson´s Disease.


Condition Intervention Phase
Idiopathic Parkinson's Disease
Drug: Rotigotine
Other: Placebo
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: A Multicenter, Multinational, Double-Blind, Placebo-Controlled, 3-Arm, Phase 4 Study To Evaluate The Efficacy Of Rotigotine On Parkinson's Disease-Associated Apathy, Motor Symptoms, And Mood

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 the Score of the Apathy Evaluation Scale (AS) Rated by the Patient [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline) ] [ Designated as safety issue: No ]

    The Apathy Scale (AS) is an abbreviated version of the Apathy Evaluation Scale. The AS (Starkstein et al, 1992) consists of 14 items phrased as questions by the examiner that are to be answered on a 4-point Likert scale. It was developed specifically for subjects with Parkinson's disease because the Apathy Evaluation Scale was considered too demanding.

    The questions comprising the AS were answered by the subject. The total scores for Apathy Evaluation Scale ranges from 0 (best possible outcome) to 42 (worst possible outcome).


  • Change From Baseline to the End of the Maintenance Period in the Total Score of the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II (Activities of Daily Living) + III (Motor Symptoms) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline) ] [ 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.


Secondary Outcome Measures:
  • Change From Baseline to the End of the Maintenance Period in the Score of the Apathy Evaluation Scale (AS) Rated by the Caregiver (Where Available) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline) ] [ Designated as safety issue: No ]

    The Apathy Scale (AS) is an abbreviated version of the Apathy Evaluation Scale. The AS (Starkstein et al, 1992) consists of 14 items phrased as questions by the examiner that are to be answered on a 4-point Likert scale. It was developed specifically for subjects with Parkinson's disease because the Apathy Evaluation Scale was considered too demanding.

    The questions comprising the AS were answered by the caregiver. The questions were asked in a structured interview format. The caregiver was interviewed by appropriate medical staff and asked questions about the subject in the third person.The total scores for Apathy Evaluation Scale ranges from 0 (best possible outcome) to 42 (worst possible outcome).


  • 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 / Early Withdrawal (up to 19 weeks after Baseline) ] [ 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 collects 8 items with 5 categories each (0=never, 1=occasionally, 2=sometimes, 3=often, 4=always or cannot do at all). The total score was calculated by summing the scores of all applicable questions and convert the resulting sum to a summary index score between 0 and 100 by multiplying with 100/32. A negative value indicates an improvement.

  • Change From Baseline to the End of the Maintenance Period in the Sum Score of the Mood / Cognition Domain of the Nonmotor Symptom Assessment Scale (NMSS) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline) ] [ Designated as safety issue: No ]

    Nonmotor performance was assessed via the Nonmotor Symptom Assessment Scale (NMSS), an accepted scale that has been validated in an international study (Naidu et al, 2006; Chaudhuri et al, 2007), at the Baseline Visit as well as at the end of the Maintenance Period. The severity and frequency of the subject's nonmotor symptoms were assessed by the investigator (or designee) in the following 9 domain categories: cardiovascular, including falls; sleep/fatigue; mood/cognition; perceptual problems/hallucinations; attention/memory; gastrointestinal tract; urinary; sexual function; and miscellaneous.

    Items are scored for severity (from 0 (none) to 3 (severe)) and frequency (from 1 (rarely) to 4 (very frequent )). The score was calculated as severity x frequency. The theoretical minimum is 0 (best possible outcome) and maximum total score is 360 points (worst possible outcome).


  • Change From Baseline to the End of the Maintenance Period in the Sum Score of the Snaith Hamilton Pleasure Scale (SHAPS) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline) ] [ Designated as safety issue: No ]
    The Snaith Hamilton Pleasure Scale (SHAPS) (Snaith et al, 1995) is a self-report instrument developed for the assessment of hedonic capacity. The sum of the 14 items scores range from 0 to 14. A higher score represents more anhedonic symptoms.

  • Change From Baseline to the End of the Maintenance Period in the Sum Score of the Beck Depression Inventory Second Edition (BDI-II) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline) ] [ Designated as safety issue: No ]
    The Beck Depression Inventory (BDI) is a self-report instrument to measure depression symptoms and severity (Beck et al, 1961). The BDI-II is a revised version of the scale in order to be more consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for depression (Beck et al, 1996). There are 21 items in the BDI-II, classified as cognitive-affective (Items 1-13) and somatic-performance (Items 14-21) subscales. The degree of severity is indicated on a 4-point scale; items are rated from 0 (not at all) to 3 (extreme form of each symptom). Scores of 0-13 indicate minimal depression, 14-19 indicate mild depression, 20-28 indicate moderate depression, and 29-63 indicate severe depression.

  • Change From Baseline to the End of the Maintenance Period in the Sum Score of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Subscale) in "on" State [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline) ] [ Designated as safety issue: No ]

    Part III of the Unified Parkinson's Disease Rating Scale (UPDRS) 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.

    The UPDRS Part III (motor subscale) had to be measured in the "on" state and consisted of 27 items and sub items scored between 0 and 4. The sum score ranged between 0 and 108 and was calculated as sum of the 27 individual scores. If 1 or more items were missing and could not be substituted with a previous post-Baseline value, the sum score was also missing.

    A negative value indicates an improvement.


  • Change From Baseline to the End of the Maintenance Period in the Score of the Clinical Global Impression Scale (CGI) Item I (Severity of Illness) [ Time Frame: Baseline (Visit 2) until End of the Maintenance Period/Early Withdrawal (up to 19 weeks after Baseline) ] [ Designated as safety issue: No ]

    The Clinical Global Impression (CGI) scales (Guy and Bonato, 1970) were initially developed for a risk-benefit estimation within the treatment of mentally ill patients. The 4 global scales (severity of illness, change in severity from Baseline, therapeutic efficacy, and tolerability of treatment) are used as different measures of treatment outcome in different kinds of pharmacological studies.

    The CGI Item 1 (severity of illness) collected 1 answer out of 8 categories (0-'Not assessed', 1-'Normal, not at all ill', 2-'Borderline ill', 3-'Mildly ill', 4-'Moderately ill', 5-'Markedly ill', 6-'Severely ill', and 7-'Among the most extremely ill patients') at each assessment. The category 0-'Not assessed' was considered as missing and therefore used neither for calculation nor for display purposes.



Enrollment: 122
Study Start Date: February 2013
Study Completion Date: March 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rotigotine, high dose
Rotigotine, transdermal patches, maximal 16 mg / 24 hours for patients with advanced Parkinson's Disease and 8 mg / 24 hours for those with early Parkinson's Disease
Drug: Rotigotine

Rotigotine, transdermal patches:

10 cm2 (2 mg / 24 hours); 20 cm2 (4 mg / 24 hours); 30 cm2 (6 mg / 24 hours); 40 cm2 (8 mg / 24 hours)

The maximum Rotigotine dose allowed is 8 mg / 24 hours or 16 mg / 24 hours for patients with advanced Parkinson's Disease and 6 mg / 24 hours or 8 mg / 24 hours for those with early Parkinson's Disease Duration: up to 21 weeks (including de-escalation)

Other Name: (6S)-6-propyl-[2 (2 thienyl)ethyl]amino-5,6,7,8-tetrahydro-1-naphthalenol
Experimental: Rotigotine, low dose
Rotigotine, transdermal patches, optimal dose, maximal 8 mg / 24 hours for patients with advanced Parkinson's Disease and 6 mg / 24 hours for those with early Parkinson's Disease
Drug: Rotigotine

Rotigotine, transdermal patches:

10 cm2 (2 mg / 24 hours); 20 cm2 (4 mg / 24 hours); 30 cm2 (6 mg / 24 hours); 40 cm2 (8 mg / 24 hours)

The maximum Rotigotine dose allowed is 8 mg / 24 hours or 16 mg / 24 hours for patients with advanced Parkinson's Disease and 6 mg / 24 hours or 8 mg / 24 hours for those with early Parkinson's Disease Duration: up to 21 weeks (including de-escalation)

Other Name: (6S)-6-propyl-[2 (2 thienyl)ethyl]amino-5,6,7,8-tetrahydro-1-naphthalenol
Placebo Comparator: Placebo
Placebo transdermal patches
Other: Placebo

Placebo, matching transdermal patches

Duration: up to 21 weeks (including de-escalation)


  Eligibility

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

Inclusion Criteria:

  • Patients with early or advanced idiopathic Parkinson's Disease
  • Patients with advanced idiopathic Parkinson's Disease: intake of Levodopa on a stable dose of at least 200 mg/day
  • Unsatisfactory control of Parkinson's Disease motor symptoms under current treatment
  • Patients experiencing Apathy associated with Parkinson's Disease
  • Hoehn and Yahr stage score of I to IV
  • Mini-Mental State Examination score ≥ 25
  • If an antidepressant drug is taken, the dose must be stable

Exclusion Criteria:

  • Therapy with a Dopamine agonist
  • Discontinuation from pervious therapy with a dopamine agonist after an adequate length of treatment, at adequate dose, due to lack of efficacy
  • Any medical or psychiatric condition that jeopardizes / compromises patient's ability for participation
  • Patient has received Neuroleptics, Dopamine releasing substances, Dopamine modulating substances, Alpha-Methyldopa, Metoclopramide, MAO-A inhibitors, Budipine, or Tolcapone
  • Electroconvulsive therapy
  • Patient has a

    • current/anticipated psychotherapy or behavior therapy
    • history of deep brain stimulation
    • history of suicide attempt or has suicidal ideation
    • impulse control disorder
    • severe Depression
  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: NCT01782222

  Show 42 Study Locations
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: NCT01782222     History of Changes
Other Study ID Numbers: PD0005, 2012-002840-26
Study First Received: January 30, 2013
Results First Received: December 15, 2014
Last Updated: January 16, 2015
Health Authority: Austria: Agency for Health and Food Safety
Bulgaria: Bulgarian Drug Agency
Croatia: Ministry of Health and Social Care
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Poland: Ministry of Health
Romania: National Medicines Agency
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
Slovenia: Agency for Medicinal Products - Ministry of Health
Spain: Ministry of Health
Turkey: Ministry of Health
Ukraine: Ministry of Health
United States: Food and Drug Administration

Keywords provided by UCB Pharma:
Parkinson's Disease
Rotigotine
Apathy
Nonmotor
Motor
Neupro

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 June 29, 2015