Clinical trial NCT01536015: Effect of Rotigotine on Motor Symptoms in Patients With Advanced Parkinson's Disease (PD) With Motor Fluctuations and Symptoms of Gastrointestinal Dysfunction
Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Assess the Effect of Rotigotine on Motor Symptoms in Patients With Advanced Parkinson's Disease With Motor Fluctuations and Symptoms of Gastrointestinal Dysfunction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Advanced Parkinson's Disease
Keywords: Rotigotine
Neupro®
Levodopa
Gastrointestinal Dysfunction
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2012-02-20
Enrollment: 25
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 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

Primary outcomes:
measure: Change in Rotigotine Versus Placebo in the Absolute Time Spent "Off" From Baseline to the End of the 7-week Maintenance Period
timeFrame: Baseline to 10 weeks
Secondary outcomes:
measure: 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 Period
timeFrame: Baseline to 10 weeks
measure: Change in Predictability of "Off" Time (Using MDS UPDRS Part IV Item 4.5) From Baseline to End of the 7-week Maintenance Period
timeFrame: Baseline to 10 weeks
measure: Change in Score on Gastrointestinal Neurodegenerative Scale (GIND) From Baseline to the End of the of the 7-week Maintenance Period
timeFrame: Baseline to 10 weeks
measure: Change in Score on Fatigue Severity Scale (FSS) From Baseline to the End of 7-week Maintenance Period
timeFrame: Baseline to 10 weeks
measure: Change in Score on Parkinson's Disease Questionnaire (PDQ8) From Baseline to the End of 7-week Maintenance Period
timeFrame: Baseline to 10 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 011
state: Alabama
city: Gilbert
country: United States
facility: 001
state: Arizona
city: Fountain Valley
country: United States
facility: 022
state: California
city: Irvine
country: United States
facility: 017
state: California
city: Pasadena
country: United States
facility: 028
state: California
city: Sunnyvale
country: United States
facility: 015
state: California
city: Gainesville
country: United States
facility: 008
state: Florida
city: Miami
country: United States
facility: 009
state: Florida
city: Ormond Beach
country: United States
facility: 010
state: Florida
city: Sunrise
country: United States
facility: 006
state: Florida
city: Annapolis
country: United States
facility: 032
state: Maryland
city: Lincoln
country: United States
facility: 027
state: Nebraska
city: Commack
country: United States
facility: 016
state: New York
city: Mineola
country: United States
facility: 026
state: New York
city: Charlotte
country: United States
facility: 034
state: North Carolina
city: Raleigh
country: United States
facility: 002
state: North Carolina
city: Salisbury
country: United States
facility: 007
state: North Carolina
city: Toledo
country: United States
facility: 021
state: Ohio
city: Tulsa
country: United States
facility: 023
state: Oklahoma
city: Cordova
country: United States
facility: 031
state: Tennessee
city: Memphis
country: United States
facility: 018
state: Tennessee
city: Houston
country: United States
facility: 014
state: Texas
city: Richmond
country: United States
facility: 030
state: Virginia
city: Virginia Beach
country: United States
facility: 003
state: Virginia
city: Kirkland
country: United States
facility: 012
state: Washington
city: Milwaukee
country: United States
facility: 013
state: Wisconsin
Study officials:
affiliation: 877-822-9493
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References: