Safety and Tolerability Trial of Switching From Ropinirole to Rotigotine

Study Overview
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Brief Summary
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This is a Phase 3b, open-label, multicenter trial to assess the safety and tolerability of switching from ropinirole therapy to the rotigotine transdermal system and its effect on symptoms in subjects with idiopathic Parkinson's disease

Official Title
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A Phase 3b, Open-Label, Multicenter Trial to Assess the Safety and Tolerability of Switching Korean Subjects From Ropinirole to the Rotigotine Transdermal System and Its Effect on Symptoms in Idiopathic Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Rotigotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is informed and given ample time and opportunity to think about his/her participation in this trial and has given his/her written informed consent. Subject is willing and able to comply with all trial requirements. Subject is male or female, aged≥ 18 years. Subject is Korean. Subjects with idiopathic Parkinson's disease (Hoehn and Yahr Stage I-IV) as defined by the cardinal sign, bradykinesia, and at least 1 of the following: resting tremor, rigidity, or impairment of postural reflexes. Subject is not satisfactorily controlled on a total daily dose of ropinirole from 3mg to 12mg, inclusive. If the subject is receiving levodopa, either short-acting or sustained-release (in combination with benserazide or carbidopa), the total daily dose must be stable for 28 days prior to the Baseline Visit and must remain stable for the Treatment Period. If the subject is receiving an anticholinergic agent (eg, benztropine, trihexyphenidyl, parsitan, procyclidine, biperiden), a monoamine oxidase B (MAO-B) inhibitor (eg, selegiline), a COMT inhibitor (eg, entacapone), 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 the Baseline Visit and must be maintained on that dose for the Treatment Period Exclusion Criteria: Subjects are not permitted to enroll in the trial if any of the following criteria are met: Subject has previously participated in a trial with rotigotine. Subject has participated in another trial of an investigational drug within 28 days prior to the Baseline Visit or is currently participating in another trial of an investigational drug. Subject has atypical Parkinsonian syndrome(s), including drug-induced Parkinsonian syndrome(s). Subject has dementia, active psychosis, or hallucinations (not due to antiparkinsonian medication). Subject is receiving therapy with 1 of the following drugs either concurrently or within 28 days prior to Baseline Visit: alpha-methyl dopa, metoclopramide, reserpine, neuroleptics (except specific atypical neuroleptics: olanzapine, ziprasidone, aripiprazole, clozapine, quetiapine), monoamine oxidase A (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 the Baseline Visit and is likely to remain stable for the duration of the trial. Subject has a history of seizures or stroke within 1 year, has had a Transient Ischemic Attack (TIA) within 12 months prior to enrollment, or a history of myocardial infarction within the last 6 months prior to enrollment. Presence of clinically relevant hepatic dysfunction. Presence of clinically relevant renal dysfunction. Evidence of clinically relevant cardiovascular disorders. Subject has a QTcB interval of ≥ 500ms at Pretreatment or Baseline (repeated measurements within 1 hour). Subject has a history of symptomatic (not asymptomatic) orthostatic hypotension in the 6 months prior to Baseline. Subject has a history of significant skin hypersensitivity to adhesive or other transdermals or recent unresolved contact dermatitis. Subject has malignant neoplastic disease requiring therapy within 12 months prior to enrollment. Subject has a history of chronic alcohol or drug abuse within the last 6 months. Subject has taken herbal medicine therapy within the last 2 weeks prior to the Baseline Visit. Subject has clinically significant laboratory results that, in the judgment of the investigator, would make the subject unsuitable for entry into the trial. 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 1 barrier method), or (iii) not sexually abstinent or (iv) not at least 2 years postmenopausal. Subject has evidence of an impulse control disorder according to the Jay Modified Minnesota Impulsive Disorders Interview (mMIDI) at Pretreatment (Visit 1). Subject has any other clinically significant medical or psychiatric condition that would, in the judgment of the investigator, interfere with the subject's ability to participate in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotigotine<br>Patients were dispensed rotigotine patches up to 8mg/24h at a dose considered by the investigator to be equivalent to the dose of ropinirole that the subject was currently taking. | Drug: Rotigotine<br>* Strength: 2,4,6,and 8mg/24h, form: transdermal application, once daily application<br>* Other names: Neupro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pulse Rate (Supine, After 1 Minute) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Systolic Blood Pressure (Supine, After 1 Minute) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Diastolic Blood Pressure (Supine, After 1 Minute) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Pulse Rate (Supine, After 5 Minutes) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Systolic Blood Pressure (Supine, After 5 Minutes) | Change = 28 day value minus baseline value. | Baseline, 28 Days | 
| Change in Diastolic Blood Pressure (Supine, After 5 Minutes) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Pulse Rate (Standing, After 1 Minute) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Systolic Blood Pressure (Standing, After 1 Minute) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Diastolic Blood Pressure (Standing, After 1 Minute) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Pulse Rate (Standing, After 3 Minutes) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Systolic Blood Pressure (Standing, After 3 Minutes) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Diastolic Blood Pressure (Standing, After 3 Minutes) | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Heart Rate | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in PR Interval | The PR interval is defined as the period that extends from the onset of atrial depolarization (beginning of the P wave) until the onset of ventricular depolarization (beginning of the QRS complex). Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in QRS Duration | The QRS duration represents the time it takes for ventricular depolarization to occur. Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in QT Interval | The QT interval is the period that extends from the beginning of ventricular depolarization until the end of ventricular repolarization. Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) | The QT interval is the period that extends from the beginning of ventricular depolarization until the end of ventricular repolarization. Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Percentage of Basophilic Granulocytes in White Blood Cell Count | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Percentage of Eosinophilic Granulocytes in White Blood Cell Count | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Hematocrit | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Hemoglobin | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Percentage of Lymphocytes in White Blood Cell Count | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Percentage of Monocytes in White Blood Cell Count | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Percentage of Neutrophilic Granulocytes Segmented in White Blood Cell Count | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Platelet Count | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Red Blood Cell Count | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in White Blood Cell Count | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Albumin | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Alkaline Phosphatase | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Blood Urea Nitrogen | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Calcium | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Chloride | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Creatinine | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Gamma-Glutamyltransferase | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Glucose | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Inorganic Phosphate | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Potassium | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Serum Glutamic Oxaloacetic Transaminase | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Glutamic Pyruvic Transaminase | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Sodium | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Total Bilirubin | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Total Protein | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Uric Acid | Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Ears, Eyes, Nose, Mouth, Throat' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Psychiatric' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Hematological/Lymphatic Nodes' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Dermatological' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Cardiovascular' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Peripheral Vascular' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Pulmonary' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Musculoskeletal' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Hepato-/Gastrointestinal' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Renal/Genitourological' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Metabolic/Endocrine' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Other' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Mental Status' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Deep Tendon Reflexes' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Muscle Strength' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Cranial Nerve Function' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Plantar Reflex' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Gait' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Coordination/Balance' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Involuntary Movements' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Sensory Perception' |  | 28 days | 
| Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Other' |  | 28 days | 
| Completion of Trial From Baseline to End of Treatment |  | Baseline, 28 days | 
| Completion of Trial on the Original Treatment Assignment From Baseline to End of Treatment |  | Baseline, 28 days | 
| Drop-out During the 5 Half-life Overlap Period Due to Adverse Events (AEs) |  | Baseline, 2 days | 
| Drop-out Due to Adverse Events (AEs) With Onset During the 5 Half-life Overlap Period |  | Baseline, 56 days | 
| Dose Reduction During the 5 Half-life Overlap Period Due to Adverse Events (AEs) |  | Baseline, 2 days | 
| Dose Reduction Due to Adverse Events (AEs) With Onset During the 5 Half-life Overlap Period |  | Baseline, 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score From Baseline to End of Treatment | The UPDRS is a scale for the assessment of function in Parkinson's disease UPDRS Part I measures 'Mentation, Behavior and Mood'. Range: 0 (Best score possible) to 16 (Worst score possible) Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score From Baseline to End of Treatment | The UPDRS is a scale for the assessment of function in Parkinson's disease UPDRS Part II measures 'Activities in Daily Living'. Range: 0 (Best score possible) to 52 (Worst score possible) Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to End of Treatment | The UPDRS is a scale for the assessment of function in Parkinson's disease UPDRS Part III measures 'Motor Examination'. Range: 0 (Best score possible) to 56 (Worst score possible) Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score From Baseline to End of Treatment | The UPDRS is a scale for the assessment of function in Parkinson's disease UPDRS Part IV measures 'Complications of Therapy'. Range: 0 (Best score possible) to 23 (Worst score possible) Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Parkinson's Disease Sleep Scale (PDSS) Sum Score From Baseline to End of Treatment | The PDSS is a scale to assess sleep and nocturnal disability in Parkinson's disease. Range: 0 (Best score possible) to 60 (Worst score possible) Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Epworth Sleepiness Scale (ESS) Sum Score From Baseline to End of Treatment | The ESS is a self-administered questionnaire in which the subject rates the probability of his/her dozing during 8 situations that are differently conductive to sleep Range: 0 (Best score possible) to 24 (Worst score possible) Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Parkinson's Disease Non-Motor Symptom Assessment Scale (PDNMS) Total Sum Score From Baseline to End of Treatment | The PDNMS is a rating by the clinician to assess the severity and frequency of non-motor symptoms in Parkinson's disease patients Range: 0 (Best score possible) to 384 (Worst score possible) Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Change in Clinical Global Impression (CGI) Item 1 Score From Baseline to End of Treatment | The CGI is a set of ratings made by a clinician in order to assess the overall severity of an individual's symptoms as well as changes in his/her functioning over time. Item 1 measures 'Severity of Parkinson's Disease'. Range: 1 (Normal, not ill at all) to 7 (Among the most extremely ill patients) Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Clinical Global Impression (CGI) Item 2 Score | The CGI is a set of ratings made by a clinician in order to assess the overall severity of an individual's symptoms as well as changes in his/her functioning over time. Item 2 measures 'Global Improvement'. Range 1 (Very much improved) to 7 (Very much worse) | 28 days | 
| Clinical Global Impression (CGI) Item 3.1 | The CGI is a set of ratings made by a clinician in order to assess the overall severity of an individual's symptoms as well as changes in his/her functioning over time. Item 3.1 measures 'Therapeutic Effect'. Range: 1 (Marked - Vast improvement. Complete or nearly complete remission of all symptoms.) to 4 (Unchanged or worse) | 28 days | 
| Clinical Global Impression (CGI) Item 3.2 | The CGI is a set of ratings made by a clinician in order to assess the overall severity of an individual's symptoms as well as changes in his/her functioning over time. Item 3.2 measures 'Therapeutic Side Effects'. Range: 1 (None) to 4 (Outweigh the therapeutic effect) | 28 days | 
| Patient Global Impression (PGI) Item 1 Score | The PGI is a set of ratings made by the patient in order to assess the overall severity of an individual's symptoms as well as changes in his/her functioning over time. Item 1 measures 'Global Improvement'. Range: 1 (Very much improved) to 7 (Very much worse) | 28 days | 
| Patient Global Impression (PGI) Item 2 | The PGI is a set of ratings made by the patient in order to assess the overall severity of an individual's symptoms as well as changes in his/her functioning over time. Item 2 measures 'Therapeutic Effect'. Range: 1 (Marked - Vast improvement. Complete or nearly complete remission of all symptoms) to 4 (Unchanged or worse) | 28 days | 
| Patient Global Impression (PGI) Item 3 | The PGI is a set of ratings made by the patient in order to assess the overall severity of an individual's symptoms as well as changes in his/her functioning over time. Item 3 measures 'Side Effects'. Range: 1 (I have no side effects) to 4 (They outweigh the therapeutic effect of the trial medication) | 28 days | 
| Change in Short-form Parkinson's Disease Questionnaire (PDQ-8) Single Index Score From Baseline to End of Treatment | The PDQ-8 is a self-administered 8-item questionnaire that assesses issues associated with Parkinson's disease. Range: 0 (good health) to 100 (poor health) Change = 28 day value minus baseline value. | Baseline, 28 days | 
| Patient Treatment Preference Scale Question 1 | Have you used pharmaceutical treatments for your Parkinson's disease before the study? | 28 days | 
| Patient Treatment Preference Scale Question 2 | Why did you decide to enter this study? | 28 days | 
| Patient Treatment Preference Scale Question 3 | In comparing the patch and previous oral treatments for Parkinson's disease, how satisfied have you been with oral medication / patch? | 28 days | 
| Patient Treatment Preference Scale Question 4 | I would prefer using a patch over taking a pill or capsule for treatment of my Parkinson's disease. | 28 days | 
| Patient Treatment Preference Scale Question 5 | I would prefer applying one 40cm**2 patch over applying two 20cm**2 patches for treatment of my Parkinson's disease. | 28 days | 
| Patient Treatment Preference Scale Question 6 | What aspects do you like the most about the patch? | 28 days | 
| Patient Treatment Preference Scale Question 7 | What aspects do you like the least about the patch? Check all that apply. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotigotine, NEUPRO, Switching trial from ropinirole to rotigotine,, safety and tolerability, Parkinson disease