Safety and Tolerability Trial of Switching From Ropinirole to Rotigotine

Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00593606
• Other study ID #: SP0908
• Status: Completed
• Phase: Phase 3
• First received: December 21, 2007
• Last updated: September 24, 2014
• Start date: July 2007
• Est. completion date: December 2007

Study information

• Verified date: October 2011
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Rotigotine
Strength: 2,4,6,and 8mg/24h, form: transdermal application, once daily application

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

References & Publications (1)

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: 10.1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Pulse Rate (Supine, After 1 Minute)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Systolic Blood Pressure (Supine, After 1 Minute)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Diastolic Blood Pressure (Supine, After 1 Minute)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Pulse Rate (Supine, After 5 Minutes)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Systolic Blood Pressure (Supine, After 5 Minutes)	Change = 28 day value minus baseline value.	Baseline, 28 Days	No
Primary	Change in Diastolic Blood Pressure (Supine, After 5 Minutes)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Pulse Rate (Standing, After 1 Minute)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Systolic Blood Pressure (Standing, After 1 Minute)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Diastolic Blood Pressure (Standing, After 1 Minute)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Pulse Rate (Standing, After 3 Minutes)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Systolic Blood Pressure (Standing, After 3 Minutes)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Diastolic Blood Pressure (Standing, After 3 Minutes)	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Heart Rate	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	Change in Percentage of Basophilic Granulocytes in White Blood Cell Count	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Percentage of Eosinophilic Granulocytes in White Blood Cell Count	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Hematocrit	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Hemoglobin	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Percentage of Lymphocytes in White Blood Cell Count	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Percentage of Monocytes in White Blood Cell Count	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Percentage of Neutrophilic Granulocytes Segmented in White Blood Cell Count	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Platelet Count	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Red Blood Cell Count	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in White Blood Cell Count	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Albumin	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Alkaline Phosphatase	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Blood Urea Nitrogen	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Calcium	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Chloride	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Creatinine	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Gamma-Glutamyltransferase	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Glucose	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Inorganic Phosphate	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Potassium	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Serum Glutamic Oxaloacetic Transaminase	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Glutamic Pyruvic Transaminase	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Sodium	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Total Bilirubin	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Total Protein	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Change in Uric Acid	Change = 28 day value minus baseline value.	Baseline, 28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Ears, Eyes, Nose, Mouth, Throat'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Psychiatric'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Hematological/Lymphatic Nodes'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Dermatological'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Cardiovascular'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Peripheral Vascular'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Pulmonary'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Musculoskeletal'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Hepato-/Gastrointestinal'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Renal/Genitourological'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Metabolic/Endocrine'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Physical Examination for 'Other'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Mental Status'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Deep Tendon Reflexes'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Muscle Strength'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Cranial Nerve Function'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Plantar Reflex'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Gait'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Coordination/Balance'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Involuntary Movements'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Sensory Perception'		28 days	No
Primary	Occurrence of Abnormal, Clinically Relevant Events in Neurological Examination for 'Other'		28 days	No
Primary	Completion of Trial From Baseline to End of Treatment		Baseline, 28 days	No
Primary	Completion of Trial on the Original Treatment Assignment From Baseline to End of Treatment		Baseline, 28 days	No
Primary	Drop-out During the 5 Half-life Overlap Period Due to Adverse Events (AEs)		Baseline, 2 days	No
Primary	Drop-out Due to Adverse Events (AEs) With Onset During the 5 Half-life Overlap Period		Baseline, 56 days	No
Primary	Dose Reduction During the 5 Half-life Overlap Period Due to Adverse Events (AEs)		Baseline, 2 days	No
Primary	Dose Reduction Due to Adverse Events (AEs) With Onset During the 5 Half-life Overlap Period		Baseline, 56 days	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Patient Treatment Preference Scale Question 1	Have you used pharmaceutical treatments for your Parkinson's disease before the study?	28 days	No
Secondary	Patient Treatment Preference Scale Question 2	Why did you decide to enter this study?	28 days	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Patient Treatment Preference Scale Question 6	What aspects do you like the most about the patch?	28 days	No
Secondary	Patient Treatment Preference Scale Question 7	What aspects do you like the least about the patch? Check all that apply.	28 days	No

External Links

•   Clinical Study Summary on UCB.com
•   FDA Safety Alerts and Recalls
•   Product Information