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Effect of Rotigotine on Motor Symptoms in Patients With Advanced Parkinson's Disease (PD) With Motor Fluctuations and Symptoms of Gastrointestinal Dysfunction

Phase 3
Terminated
Conditions
Advanced Parkinson's Disease
Interventions
Drug: Placebo
Registration Number
NCT01536015
Lead Sponsor
UCB Pharma
Brief Summary

The primary purpose is to demonstrate superiority of Rotigotine over Placebo on motor symptoms when used in subjects with symptoms of Gastrointestinal Dysfunction. Hypothesis: Rotigotine will decrease OFF time compared to Placebo.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
25
Inclusion Criteria
  • Subject is informed and given ample time and opportunity to think about his/her participation in this study and has given his/her written informed consent on an Institutional Review Board approved consent form

  • Subject is willing and able to comply with all study requirements (protocol, visit schedule, procedures, and medication application)

  • Subject is male or female and ≥ 30 years of age

  • Subject has Idiopathic Parkinson's Disease of more than 3 years duration, as defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the following: resting tremor, rigidity, impairment of postural reflexes; and is without any other known or suspected cause of Parkinsonism

  • Subject has a Hoehn & Yahr stage score II through IV

  • Subject must be on a stable dose of L-dopa, either short-acting or sustained release (in combination with Benserazide or Carbidopa), of at least 200 mg/day administered in at least 2 intakes, for at least 21 days prior to starting Parkinson's diaries

  • Subject must be able to differentiate between the "on" and "off" state (and thereby be able to recognize the Time To "On" (TTON)), and be willing and able to accurately complete a Parkinson's Disease subject diary on designated days (with assistance from caregivers, if required)

  • Subject must complete 6 Parkinson's diaries over a period of 6 days, with 4 of the 6 Parkinson's diaries being "valid" as determined by the investigator. The "valid" Parkinson's diaries confirm that the subject has an average of at least 2.5 h/day spent in the "off" state

  • Subject receiving a Monoamine Oxidase (MAO)-B Inhibitor (eg, Selegiline or Rasagiline), an n-Methyl-d-Aspartate Antagonist (eg, Amantadine), or allowed anti-Parkinson medications and has been on a stable dose for at least 21 days prior to starting Parkinson's diaries and is anticipated to be maintained on that dose for the duration of the study

  • Subject has clinical symptoms of Gastrointestinal Dysfunction (GID) confirmed by at least 1 of the following

    •Parkinson's disease-related GI symptoms as per the Gastrointestinal Degenerative Scale (GIND) Scale: defecatory dysfunction, constipation, excessive gas, abdominal pain, bloating, nausea, vomiting, anorexia, early satiety, or weight loss (except sialorrhea and dysphagia)

  • Female subjects of childbearing potential must agree to use 1 of the following contraceptive methods: oral contraceptive, intrauterine device, or double-barrier method, throughout the study and for 2 weeks after the removal of study medication

Exclusion Criteria
  • Subject has previously participated in this study
  • Subject has participated in another study of an investigational medicinal product (IMP) or a medical device within the last 30 days or is currently participating in another study of an IMP or a medical device
  • Subject has an Atypical Parkinsonian Syndrome due to drugs (eg, Metoclopramide, Flunarizine), Metabolic Neurogenetic Disorders (eg, Wilson's Disease), Encephalitis, Cerebrovascular Disease, or Degenerative Disease (eg, Progressive Supranuclear Palsy)
  • Subject has a history of Pallidotomy, Thalamotomy, Deep Brain Stimulation, or Fetal Tissue Transplant
  • Subject has Dementia, Active Psychosis, or Hallucinations
  • Subject exhibits Dopaminergic Dysregulation Syndrome
  • Subject is receiving therapy with certain medications in a specific timeframe as specified in the protocol
  • Subject has history of chronic Gastrointestinal (GI) Disease not related to Parkinson's disease which in the judgement of the investigator may affect the ability of the subject to participate in the study (ie, Irritable Bowel Syndrome, Diverticulitis, Crohn's Disease, etc) or GI/abdominal surgery (except for Appendectomy, Hysterectomy, or Cholecystectomy)
  • Subject has had any GI surgery in the 3 months prior to the Screening Visit
  • Subject has a current diagnosis of Epilepsy, has a history of seizures as an adult, or has a history of stroke or Transient Ischemic Attack within 1 year prior to the Screening Visit
  • Subject has clinically relevant Hepatic or Renal Dysfunction
  • Subject has clinically relevant Cardiac Dysfunction (any cardiac disorder that in the opinion of the investigator would put the subject at risk of clinically relevant arrhythmia)
  • Subject has had a Myocardial Infarction within the last 1 year prior to the Screening Visit
  • Subject has a history of Symptomatic (not Asymptomatic) Orthostatic Hypotension
  • Subject has a Systolic Blood Pressure (BP) < 105 mmHg at the Screening Visit
  • Subject has a history of chronic alcohol or drug abuse within the prior 6 months
  • Female subject is pregnant or lactating
  • Subject (male or female) is of child bearing potential but not surgically sterile or not using adequate birth control methods
  • Subject has evidence of an Impulse Control Disorder according to the Modified Minnesota Impulsive Disorders Interview (mMIDI) at the Screening Visit
  • Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at the Screening Visit
  • Subject has a significant skin disease/condition that would make transdermal drug use inappropriate, including a history of skin sensitivity to adhesives or other transdermal medications
  • Subject has a known hypersensitivity to any components of the Rotigotine patch, including Sodium Metabisulfite
  • Subject has any medical, psychiatric, or cognitive condition, or laboratory abnormality that would, in the opinion of the investigator, jeopardize or compromise the subject's well-being or ability to participate in the study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo patch.
RotigotineRotigotineRotigotine patch titrated from 4 mg/24 h - 8 mg/24 h or until effective or maximum dose is reached.
Primary Outcome Measures
NameTimeMethod
Change in Rotigotine Versus Placebo in the Absolute Time Spent "Off" From Baseline to the End of the 7-week Maintenance PeriodBaseline to 10 weeks

Mean number of hours marked "off" during a 24-hour period.

Secondary Outcome Measures
NameTimeMethod
Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS) Part III (Motor Examination) in the "on" State From Baseline to the End of the 7-week Maintenance PeriodBaseline to 10 weeks

The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS) Part III is an 18-item scale with each single item of the scale ranging from 0 (normal) to 4 (severe).

Change in Predictability of "Off" Time (Using MDS UPDRS Part IV Item 4.5) From Baseline to End of the 7-week Maintenance PeriodBaseline to 10 weeks

The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS) Part IV is a 6-item scale with each single item of the scale ranging from 0 (normal) to 4 (severe).

Change in Score on Gastrointestinal Neurodegenerative Scale (GIND) From Baseline to the End of the of the 7-week Maintenance PeriodBaseline to 10 weeks

Gastrointestinal Neurodegenerative Scale (GIND) is an 18-item scale measuring gastrointestinal dysfunction with each single item of the scale ranging from 0 (never or not at all) to 5 (very severe).

Change in Score on Fatigue Severity Scale (FSS) From Baseline to the End of 7-week Maintenance PeriodBaseline to 10 weeks

The Fatigue Severity Scale is a 9-item scale measuring the impact of fatigue on everyday functioning (e.g. "fatigue interferes with my work, each single item of the scale ranging from 1 (disagree) to 7 (agree).

Change in Score on Parkinson's Disease Questionnaire (PDQ8) From Baseline to the End of 7-week Maintenance PeriodBaseline to 10 weeks

The Parkinson's Disease Questionnaire (PDQ-8) is a self-administered 8-item questionnaire that assesses issues associated with Parkinson's disease. Each single item of the 8-item questionnaire ranges from 0 (never) to 4 (always).

Trial Locations

Locations (26)

014

🇺🇸

Houston, Texas, United States

032

🇺🇸

Annapolis, Maryland, United States

016

🇺🇸

Commack, New York, United States

003

🇺🇸

Virginia Beach, Virginia, United States

034

🇺🇸

Charlotte, North Carolina, United States

007

🇺🇸

Salisbury, North Carolina, United States

001

🇺🇸

Gilbert, Arizona, United States

006

🇺🇸

Sunrise, Florida, United States

027

🇺🇸

Lincoln, Nebraska, United States

018

🇺🇸

Memphis, Tennessee, United States

023

🇺🇸

Tulsa, Oklahoma, United States

031

🇺🇸

Cordova, Tennessee, United States

022

🇺🇸

Fountain Valley, California, United States

026

🇺🇸

Mineola, New York, United States

002

🇺🇸

Raleigh, North Carolina, United States

021

🇺🇸

Toledo, Ohio, United States

012

🇺🇸

Kirkland, Washington, United States

015

🇺🇸

Sunnyvale, California, United States

008

🇺🇸

Gainesville, Florida, United States

017

🇺🇸

Irvine, California, United States

028

🇺🇸

Pasadena, California, United States

010

🇺🇸

Ormond Beach, Florida, United States

011

🇺🇸

Birmingham, Alabama, United States

009

🇺🇸

Miami, Florida, United States

030

🇺🇸

Richmond, Virginia, United States

013

🇺🇸

Milwaukee, Wisconsin, United States

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