Safety and Tolerability Trial of Switching From Ropinirole to Rotigotine - Full Text View

Sponsored by:	UCB
Information provided by:	UCB
ClinicalTrials.gov Identifier:	NCT00593606

Purpose

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

Condition	Intervention	Phase
Parkinson's Disease	Drug: Rotigotine	Phase III

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia Parkinson disease

MedlinePlus related topics: Parkinson's Disease

Drug Information available for: Ropinirole hydrochloride Ropinirole Rotigotine

U.S. FDA Resources

Further study details as provided by UCB:

Primary Outcome Measures:

Change in Pulse Rate (Supine, After 1 Minute) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Systolic Blood Pressure (Supine, After 1 Minute) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Diastolic Blood Pressure (Supine, After 1 Minute) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Pulse Rate (Supine, After 5 Minutes) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Systolic Blood Pressure (Supine, After 5 Minutes) [ Time Frame: Baseline, 28 Days ] [ Designated as safety issue: No ]
Change in Diastolic Blood Pressure (Supine, After 5 Minutes) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Pulse Rate (Standing, After 1 Minute) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Systolic Blood Pressure (Standing, After 1 Minute) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Diastolic Blood Pressure (Standing, After 1 Minute) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Pulse Rate (Standing, After 3 Minutes) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Systolic Blood Pressure (Standing, After 3 Minutes) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Diastolic Blood Pressure (Standing, After 3 Minutes) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Heart Rate [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in PR Interval [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in QRS Duration [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in QT Interval [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Percentage of Basophilic Granulocytes in White Blood Cell Count [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Percentage of Eosinophilic Granulocytes in White Blood Cell Count [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Hematocrit [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Hemoglobin [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Percentage of Lymphocytes in White Blood Cell Count [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Percentage of Monocytes in White Blood Cell Count [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Percentage of Neutrophilic Granulocytes Segmented in White Blood Cell Count [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Platelet Count [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Red Blood Cell Count [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in White Blood Cell Count [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Albumin [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Alkaline Phosphatase [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Blood Urea Nitrogen [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Calcium [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Chloride [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Creatinine [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Gamma-Glutamyltransferase [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Glucose [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Inorganic Phosphate [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Potassium [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Serum Glutamic Oxaloacetic Transaminase [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Glutamic Pyruvic Transaminase [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Sodium [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Total Bilirubin [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Total Protein [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Uric Acid [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Ears, Eyes, Nose, Mouth, Throat' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Psychiatric' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Hematological/Lymphatic Nodes' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Dermatological' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Cardiovascular' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Peripheral Vascular' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Pulmonary' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Musculoskeletal' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Hepato-/Gastrointestinal' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Renal/Genitourological' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Metabolic/Endocrine' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Other' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Mental Status' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Deep Tendon Reflexes' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Muscle Strength' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Cranial Nerve Function' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Plantar Reflex' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Gait' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Coordination/Balance' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Involuntary Movements' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Sensory Perception' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Other' [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Completion of Trial From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Completion of Trial on the Original Treatment Assignment From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Drop-Out During the 5 Half-Life Overlap Period Due to Adverse Events (AEs) [ Time Frame: Baseline, 2 days ] [ Designated as safety issue: No ]
Drop-Out Due to Adverse Events (AEs) With Onset During the 5 Half-Life Overlap Period [ Time Frame: Baseline, 56 days ] [ Designated as safety issue: No ]
Dose Reduction During the 5 Half-Life Overlap Period Due to Adverse Events (AEs) [ Time Frame: Baseline, 2 days ] [ Designated as safety issue: No ]
Dose Reduction Due to Adverse Events (AEs) With Onset During the 5 Half-Life Overlap Period [ Time Frame: Baseline, 56 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Parkinson's Disease Sleep Scale (PDSS) Sum Score From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Epworth Sleepiness Scale (ESS) Sum Score From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Parkinson's Disease Non-Motor Symptom Assessment Scale (PDNMS) Total Sum Score From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Change in Clinical Global Impression (CGI) Item 1 Score From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Clinical Global Impression (CGI) Item 2 Score [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Clinical Global Impression (CGI) Item 3.1 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Clinical Global Impression (CGI) Item 3.2 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Patient Global Impression (PGI) Item 1 Score [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Patient Global Impression (PGI) Item 2 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Patient Global Impression (PGI) Item 3 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Change in Short-Form Parkinson's Disease Questionnaire (PDQ-8) Single Index Score From Baseline to End of Treatment [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
Patient Treatment Preference Scale Question 1 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Patient Treatment Preference Scale Question 2 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Patient Treatment Preference Scale Question 3 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Patient Treatment Preference Scale Question 4 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Patient Treatment Preference Scale Question 5 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Patient Treatment Preference Scale Question 6 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Patient Treatment Preference Scale Question 7 [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Enrollment:	124
Study Start Date:	July 2007
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Rotigotine: Experimental 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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Responsible Party:	UCB ( Study Director )
Study ID Numbers:	SP908
Study First Received:	December 21, 2007
Results First Received:	December 17, 2008
Last Updated:	June 5, 2009
ClinicalTrials.gov Identifier:	NCT00593606 History of Changes
Health Authority:	Korea: Food and Drug Administration