Safety and Tolerability Trial of Switching From Ropinirole to Rotigotine

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

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

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Rotigotine

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rotigotine; 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; Strength: 2,4,6,and 8mg/24h, form: transdermal application, once daily application; Other Names: Neupro

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

General Publications

• Kim HJ, Jeon BS, Lee WY, Lee MC, Kim JW, Kim JM, Ahn TB, Cho J, Chung SJ, Grieger F, Whitesides J, Boroojerdi B. Overnight switch from ropinirole to transdermal rotigotine patch in patients with Parkinson disease. BMC Neurol. 2011 Aug 10;11:100. doi: 10.1186/1471-2377-11-100.

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: January 14, 2008
• First Posted (Estimate): January 15, 2008

Study Record Updates

• Last Update Posted (Estimate): October 2, 2014
• Last Update Submitted That Met QC Criteria: September 24, 2014
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Rotigotine; Parkinson disease; NEUPRO; Switching trial from ropinirole to rotigotine,; safety and tolerability
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Rotigotine
• Other Study ID Numbers: SP0908