Clinical trial NCT01646255: Rotigotine Versus Placebo, A Study To Evaluate The Efficacy In Advanced Stage Idiopathic Parkinson's Disease Patients
Official title: A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of The Efficacy And Safety of Rotigotine Transdermal Patch In Chinese Subjects With Advanced-stage, Idiopathic Parkinson's Disease Who Are Not Well Controlled On Levodopa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Parkinson's Disease
Keywords: Rotigotine
Neupro phase 3
Advanced-stage
Idiopathic Parkinson's Disease
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
Collaborators: name: UCB Trading (Shanghai) Co. Ltd.
First posted: 2012-07-20
Enrollment: 346
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: The study included a maximum 4-week Screening Period, a maximum 7-week Titration Period for advanced-stage Parkinson's disease, 12-week Maintenance Period, a maximum 12-day De-escalation Period for advanced-stage Parkinson's Disease and 30-day Safety Follow-Up Period. The maximum study duration for an individual subject with advanced-stage Parkinson's disease was 27 weeks.

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:

Primary outcomes:
measure: Absolute Change in Absolute Time Spent 'Off' From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Secondary outcomes:
measure: Percentage of Responders From Baseline to the End of the Doubleblind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Percent Change in Absolute Time Spent "Off" From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Percent Change in Relative Time Spent "Off" From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Change in Absolute Time Spent "on" From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Change in Relative Time Spent "on" From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Percent Change in Absolute Time Spent "on" From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Percent Change in Relative Time Spent "on" From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Change in the Number of "Off" Periods From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Change in Status of the Subject (on) After Wake-up With Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Change in Status of the Subject (on) After Wake-up Without Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Change in Status of the Subject (Off) After Wake-up From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III Motor Examination) During "on" Periods From Baseline to the End of Double-blind Maintenance Period
timeFrame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Sp1037 001
city: Beijing
country: China
facility: Sp1037 002
city: Beijing
country: China
facility: Sp1037 019
city: Beijing
country: China
facility: Sp1037 025
city: Changchun
country: China
facility: Sp1037 017
city: Chengdu
country: China
facility: Sp1037 007
city: Chengdu
country: China
facility: Sp1037 027
city: Fuzhou
country: China
facility: Sp1037 021
city: Guangzhou
country: China
facility: Sp1037 010
city: Guangzhou
country: China
facility: Sp1037 011
city: Guangzhou
country: China
facility: Sp1037 014
city: Guangzhou
country: China
facility: Sp1037 015
city: Hangzhou
country: China
facility: Sp1037 005
city: Hangzhou
country: China
facility: Sp1037 013
city: Hangzhou
country: China
facility: Sp1037 018
city: Jinan
country: China
facility: Sp1037 023
city: Shanghai
country: China
facility: Sp1037 003
city: Shanghai
country: China
facility: Sp1037 004
city: Shanghai
country: China
facility: Sp1037 009
city: Suzhou
country: China
facility: Sp1037 008
city: Tianjin
country: China
facility: Sp1037 016
city: Wuhan
country: China
facility: Sp1037 006
city: Wuhan
country: China
facility: Sp1037 022
city: Wuhan
country: China
facility: Sp1037 024
Study officials:
affiliation: 1 877 822 9493
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Zhang ZX, Liu CF, Tao EX, Shao M, Liu YM, Wang J, Asgharnejad M, Xue HB, Surmann E, Bauer L. Rotigotine transdermal patch in Chinese patients with advanced Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study. Parkinsonism Relat Disord. 2017 Nov;44:6-12. doi: 10.1016/j.parkreldis.2017.08.015. Epub 2017 Aug 10.