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

Phase 4
Completed
Conditions
Idiopathic Parkinson's Disease
Interventions
Other: Placebo
Registration Number
NCT01782222
Lead Sponsor
UCB BIOSCIENCES GmbH
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
122
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo transdermal patches
Rotigotine, low doseRotigotineRotigotine, 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
Rotigotine, high doseRotigotineRotigotine, 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
Primary Outcome Measures
NameTimeMethod
Change From Baseline to the End of the Maintenance Period in the Score of the Apathy Evaluation Scale (AS) Rated by the PatientBaseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline)

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)Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline)

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
NameTimeMethod
Change From Baseline to the End of the Maintenance Period in the Sum Score of the 8-item Parkinson's Disease Questionnaire (PDQ-8)Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline)

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 Score of the Clinical Global Impression Scale (CGI) Item I (Severity of Illness)Baseline (Visit 2) until End of the Maintenance Period/Early Withdrawal (up to 19 weeks after Baseline)

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.

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)Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline)

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 Beck Depression Inventory Second Edition (BDI-II)Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline)

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 Mood / Cognition Domain of the Nonmotor Symptom Assessment Scale (NMSS)Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline)

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)Baseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline)

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 Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Subscale) in "on" StateBaseline (Visit 2) until End of the Maintenance Period / Early Withdrawal (up to 19 weeks after Baseline)

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.

Trial Locations

Locations (42)

3801

🇸🇰

Banska Bystrica, Slovakia

3506

🇵🇱

Gdynia, Poland

3003

🇦🇹

Linz, Austria

4319

🇺🇸

Asheville, North Carolina, United States

4312

🇺🇸

Cincinnati, Ohio, United States

4305

🇺🇸

San Antonio, Texas, United States

4333

🇺🇸

Virginia Beach, Virginia, United States

3805

🇸🇰

Bratislava, Slovakia

4314

🇺🇸

Decatur, Georgia, United States

4303

🇺🇸

Commack, New York, United States

3001

🇦🇹

Innsbruck, Austria

3509

🇵🇱

Gdansk, Poland

3807

🇸🇰

Zilina, Slovakia

4326

🇺🇸

Springfield, Massachusetts, United States

4318

🇺🇸

Chicago, Illinois, United States

4306

🇺🇸

Ormond Beach, Florida, United States

3301

🇭🇺

Budapest, Hungary

4316

🇺🇸

Winfield, Illinois, United States

3806

🇸🇰

Krompachy, Slovakia

3901

🇸🇮

Ljubljana, Slovenia

4307

🇺🇸

Salt Lake City, Utah, United States

4320

🇺🇸

Birmingham, Alabama, United States

4009

🇪🇸

Oviedo, Spain

4005

🇪🇸

Sevilla, Spain

4010

🇪🇸

Sevilla, Spain

4304

🇺🇸

Kansas City, Kansas, United States

4309

🇺🇸

Oxnard, California, United States

4311

🇺🇸

Palm Beach Gardens, Florida, United States

4317

🇺🇸

New York, New York, United States

4323

🇺🇸

New York, New York, United States

4330

🇺🇸

Ocean Springs, Mississippi, United States

4325

🇺🇸

Charlotte, North Carolina, United States

4001

🇪🇸

Barcelona, Spain

4322

🇺🇸

Des Moines, Iowa, United States

4302

🇺🇸

Las Vegas, Nevada, United States

4329

🇺🇸

Akron, Ohio, United States

4324

🇺🇸

Beaufort, South Carolina, United States

4006

🇪🇸

Barcelona, Spain

3302

🇭🇺

Debrecen, Hungary

4313

🇺🇸

Tampa, Florida, United States

4332

🇺🇸

Charleston, South Carolina, United States

3504

🇵🇱

Poznan, Poland

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