Rotigotine Versus Placebo, A Study To Evaluate The Efficacy In Advanced Stage Idiopathic Parkinson's Disease Patients
Condition: Idiopathic Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: Rotigotine; Placebo Patch; L-dopa
Intervention description: Transdermal Patch
Content:
4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2)
For advanced-stage Parkinson's Disease, subjects received Rotigotine patches in escalating weekly dose (starting with daily doses 4 mg/24 h to 16 mg/24 h) for a maximum 7-week Titration Period, then 12 week maintenance period; Transdermal Patch
Size:
20 cm^2, 30 cm^2, 40 cm^2
Subjects randomized to placebo received matching placebo patches; 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 28 days prior to Baseline.
Intervention MeSH terms: Levodopa; Rotigotine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 346.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: Rotigotine; Neupro phase 3; Advanced-stage; Idiopathic Parkinson's Disease

Summary:

      The primary objective of this study was to demonstrate that Rotigotine transdermal patch is
      efficacious in Chinese subjects with advanced-stage Idiopathic Parkinson's Disease as an
      adjuvant therapy.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion Criteria:

          -  An Independent Ethics Committee (IEC)-approved written informed consent is signed and
             dated by the subject or by the legal representative

          -  Subject/legal representative is considered reliable and capable of adhering to the
             protocol (eg, able to understand and complete diaries), visit schedule, and medication
             application according to the judgment of the investigator

          -  Subject has Idiopathic Parkinson's Disease of more than 3 years' duration, defined by
             the cardinal sign, Bradykinesia, plus the presence of at least 1 of the following:
             resting tremor, rigidity, or impairment of postural reflexes, and without any other
             known or suspected cause of Parkinsonism

          -  The investigator must observe the subject in both the 'on' and 'off' state and
             determine that the subject is Hoehn & Yahr stage 2 through 4 in both the 'on' and
             'off' state

          -  Subject is male or female and aged ≥30 years at Screening (Visit 1)

          -  Subject has a Mini Mental State Examination (MMSE) score of ≥25 at Screening (Visit 1)

          -  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 28 days prior to Baseline (Visit 2)

          -  Subject is not adequately controlled on a L-dopa dose (in combination with Benserazide
             or Carbidopa) which was judged by the treating physician to be optimal

          -  Subject must be willing and able to accurately complete a subject diary on designated
             days (with assistance from caregivers, if required), recording periods when they are
             'on without troublesome Dyskinesia', 'on with troublesome Dyskinesia', 'off', and
             sleeping

          -  As part of the Screening (pretreatment) assessments, the subject must complete a diary
             over a period of 6 days, with 4 of the 6 diaries being 'valid' as determined by the
             investigator (see Section 9.1.1)

          -  It must be clear to the investigator that the subject is able to differentiate between
             the 'on' and 'off' state and the 'valid' diaries confirm that the subject has an
             average of ≥2.5 h/day spent in the 'off' state

          -  If the subject is receiving an Anticholinergic agent (eg, Benztropine,
             Trihexyphenidyl, Parsitan, Procyclidine, Biperiden), a monoamine oxidase (MAO)-B
             inhibitor (eg, Selegiline), and/or an N-methyl-d-aspartate (NMDA) antagonist (eg,
             Amantadine), he/she must have been on a stable dose for at least 28 days prior to
             Baseline (Visit 2) and be maintained on that dose for the duration of the study

          -  Subject must be on a stable dose of all anti-Parkinsonian medications for at least 20
             days prior to completing the 6 Baseline diaries

        Exclusion Criteria:

          -  Subject has previously participated in this study or subject has previously received
             the study medication under investigation in this study

          -  Subject is participating in another study of an investigational drug or has done so
             within 28 days prior to the Baseline Visit (Visit 2)

          -  Subject has a history of significant skin hypersensitivity to adhesive or other
             transdermal preparations, or recent unresolved contact dermatitis

          -  Subject has a lifetime history of suicide attempt (including an actual 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 Screening (Visit 1)

          -  Subject has atypical Parkinson's syndrome(s) 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, or severe depression

          -  Subject is receiving therapy with a Dopamine agonist either concurrently or has done
             so within 28 days prior to the Baseline Visit (Visit 2)

          -  Subject is receiving therapy with 1 of the following drugs either concurrently or
             within 28 days prior to Baseline (Visit 2): Alpha-methyl dopa, Metoclopramide,
             Reserpine, Neuroleptics (except specific atypical neuroleptics: Olanzapine,
             Ziprasidone, Aripiprazole, Clozapine, quetiapine), MAO-A inhibitors, Methylphenidate,
             or Amphetamine

          -  Subject is currently receiving central nervous system (CNS) active therapy (eg,
             sedatives, hypnotics, antidepressants, anxiolytics), unless the dose has been stable
             for at least 28 days prior to Baseline (Visit 2) and is likely to remain stable for
             the duration of the study

          -  Subject has a current diagnosis of Epilepsy, has a history of seizures as an adult,
             has a history of stroke, or has had a transient ischemic attack within 1 year prior to
             Screening (Visit 1)

          -  Subject has clinically relevant hepatic dysfunction (as defined as a total bilirubin
             >2.0 mg/dL, or Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST)
             >2 times the upper limit of the reference range)

          -  Subject has clinically relevant renal dysfunction (serum creatinine >2.0 mg/dL [>178
             μmol/L])

          -  Subject has clinically relevant cardiac dysfunction (any cardiac disorder which in the
             opinion of the investigator would put the subject at risk of clinically relevant
             arrhythmia) and/or myocardial infarction within the last 12 months

          -  Subject has a QT interval corrected for heart rate according to Bazett's formula
             (QTcB) of ≥500 ms at Screening (Visit 1)

          -  Subject has a history of only symptomatic (not asymptomatic) orthostatic hypotension,
             with a decrease of systolic blood pressure (SBP) from supine to standing position of
             ≥2 0 mmHg or of ≥10 mmHg in DBP after 1 or 3 minutes within 28 days prior to Baseline
             (Visit 2), or SBP <105 mmHg at study entry 17. Subject has evidence of an impulse
             control disorder (ICD) at Screening (Visit 1)

          -  Subject has a history of known intolerance/hypersensitivity to the following
             Antiemetics: Domperidone, Trimethobenzamide, Ondansetron, Tropisetron, Granisetron,
             and Glycopyrrolate

          -  Subject has a history of chronic alcohol or drug abuse within the last 5 years

          -  Subject is pregnant or nursing, or is of childbearing potential but (i) not surgically
             sterile or (ii) not using adequate birth control methods (including at least a double
             barrier method) or (iii) not sexually abstinent or (iv) not at least 2 years
             post-menopausal

          -  Subject has any other clinically relevant medical condition, psychiatric condition, or
             laboratory abnormality which would, in the judgment of the investigator, interfere
             with the subject's ability to participate in the study

        Exclusion Criteria: