Advanced Parkinson's Disease
Conditions
Keywords
Rotigotine, Neupro®, Levodopa, Gastrointestinal Dysfunction
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.
Interventions
DRUGRotigotine
Strength and Form: 4 - 8 mg patches, one patch applied every 24 hours Dosage and Frequency: One patch every 24 hours Duration: 10 weeks
DRUGPlacebo
Frequency: One patch applied every 24 hours Duration: 10 weeks
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Rotigotine Versus Placebo in the Absolute Time Spent Off From Baseline to the End of the 7-week Maintenance Period | Baseline to 10 weeks | Mean number of hours marked off during a 24-hour period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline 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 Period | Baseline 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 Period | Baseline 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 Period | Baseline 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 Period | Baseline 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). |
Countries
United States
Participant flow
Recruitment details
The total duration of the study was to be a maximum of 19 weeks for each subject, including the Screening Period (within 50 days prior to Day 1), the Titration Period (up to 3 weeks), the Maintenance Period (up to 7 weeks), and a Safety Follow-Up Visit. The Participant Flow refers to the Randomized Set which includes all randomized subjects.
Pre-assignment details
A total of approximately 150 subjects were planned to be randomized in a 1:1 ratio to either Rotigotine or Placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo patch
Placebo: Frequency: One patch applied every 24 hours
Duration: 10 weeks | 12 |
| Rotigotine Rotigotine patch titrated from 4 mg/24 h - 8 mg/24 h or until effective or maximum dose is reached.
Rotigotine: Strength and Form: 4 - 8 mg patches, one patch applied every 24 hours
Dosage and Frequency: One patch every 24 hours
Duration: 10 weeks | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Inclusion Criterion not met | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Study closure | 5 | 5 |
Baseline characteristics
| Characteristic | Placebo | Rotigotine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 7 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Continuous | 66.1 years STANDARD_DEVIATION 8.2 | 66.7 years STANDARD_DEVIATION 9.6 | 66.4 years STANDARD_DEVIATION 8.8 |
| Body Mass Index (BMI) | 28.714 kilogram/m^2 STANDARD_DEVIATION 4.167 | 25.113 kilogram/m^2 STANDARD_DEVIATION 4.809 | 26.842 kilogram/m^2 STANDARD_DEVIATION 4.785 |
| Height | 171.79 centimeter STANDARD_DEVIATION 13.65 | 173.86 centimeter STANDARD_DEVIATION 10.61 | 172.87 centimeter STANDARD_DEVIATION 11.95 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 8 Participants | 19 Participants |
| Region of Enrollment United States | 12 participants | 13 participants | 25 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
| Weight | 84.64 kilogram STANDARD_DEVIATION 14.93 | 76.67 kilogram STANDARD_DEVIATION 19.53 | 80.50 kilogram STANDARD_DEVIATION 17.58 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 12 | 5 / 13 |
| serious Total, serious adverse events | 0 / 12 | 1 / 13 |
Outcome results
Primary
Change in Rotigotine Versus Placebo in the Absolute Time Spent Off From Baseline to the End of the 7-week Maintenance Period
Mean number of hours marked off during a 24-hour period.
Time frame: Baseline to 10 weeks
Population: This study was terminated early because of low enrollment. Due to the early termination no analysis tables of efficacy data were done and no descriptive summaries of efficacy data were produced.
Secondary
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
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).
Time frame: Baseline to 10 weeks
Population: This study was terminated early because of low enrollment. Due to the early termination no analysis tables of efficacy data were done and no descriptive summaries of efficacy data were produced.
Secondary
Change in Predictability of Off Time (Using MDS UPDRS Part IV Item 4.5) From Baseline to End of the 7-week Maintenance Period
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).
Time frame: Baseline to 10 weeks
Population: This study was terminated early because of low enrollment. Due to the early termination no analysis tables of efficacy data were done and no descriptive summaries of efficacy data were produced.
Secondary
Change in Score on Fatigue Severity Scale (FSS) From Baseline to the End of 7-week Maintenance Period
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).
Time frame: Baseline to 10 weeks
Population: This study was terminated early because of low enrollment. Due to the early termination no analysis tables of efficacy data were done and no descriptive summaries of efficacy data were produced.
Secondary
Change in Score on Gastrointestinal Neurodegenerative Scale (GIND) From Baseline to the End of the of the 7-week Maintenance Period
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).
Time frame: Baseline to 10 weeks
Population: This study was terminated early because of low enrollment. Due to the early termination no analysis tables of efficacy data were done and no descriptive summaries of efficacy data were produced.
Secondary
Change in Score on Parkinson's Disease Questionnaire (PDQ8) From Baseline to the End of 7-week Maintenance Period
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).
Time frame: Baseline to 10 weeks
Population: This study was terminated early because of low enrollment. Due to the early termination no analysis tables of efficacy data were done and no descriptive summaries of efficacy data were produced.