Effect of Rotigotine on Motor Symptoms in Patients With Advanced Parkinson's Disease (PD) With Motor Fluctuations and Symptoms of Gastrointestinal Dysfunction
Condition: Advanced Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: Rotigotine; Placebo
Intervention description: Strength and Form: 4 - 8 mg patches, one patch applied every 24 hours
Dosage and Frequency: One patch every 24 hours
Duration: 10 weeks; Frequency: One patch applied every 24 hours
Duration: 10 weeks
Intervention MeSH terms: Rotigotine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 25.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: Rotigotine; Neupro®; Levodopa; Gastrointestinal Dysfunction

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.
    

Eligibility criteria:

        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