Placebo-controlled Study in Patients With Parkinson's Disease to Evaluate the Effect of Rotigotine on Non-motor Symptoms

Idiopathic Parkinson's Disease Clinical Trial

Official title:

Multicenter, Double-blind, Placebo-controlled, Parallel-group, Phase IV Study to Assess the Effect of Rotigotine on Non-motor Symptoms in Patients With Idiopathic Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01300819
• Other study ID #: SP0976
• Secondary ID: 2010-021394-37
• Status: Completed
• Phase: Phase 4
• First received: February 18, 2011
• Last updated: April 9, 2014
• Start date: February 2011
• Est. completion date: November 2012

Study information

• Verified date: April 2014
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicinal Products and Health ProductsBulgaria: Bulgarian Drug AgencyCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyItaly: The Italian Medicines AgencyRomania: National Medicines AgencySlovakia: State Institute for Drug ControlSpain: Agencia Española de Medicamentos y Productos SanitariosSwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to demonstrate that Rotigotine improves non-motor symptoms compared to Placebo in subjects with Parkinson's Disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 349
• Est. completion date: November 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject is male or female, =18 years of age

• Subject has idiopathic Parkinson's disease with at least 2 of the following cardinal signs being present: bradykinesia, resting tremor, rigidity or postural instability, and without any other known or suspected cause of Parkinsonism

• Subject has a Hoehn and Yahr stage score =4

• Subject has a total Non-Motor Symptoms Scale (NMSS) score =40

• If the subject is taking levodopa (L-DOPA), he/she must be on a stable dose of L-DOPA (in combination with benserazide or carbidopa) for at least 28 days prior to the Baseline Visit

• If the subject is receiving anticholinergics, monoamine oxidase (MAO) B inhibitors, or 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 duration of the study

Exclusion Criteria:

• Subject discontinued from previous therapy with a dopamine agonist after an adequate length of treatment, at an adequate dose, due to lack of efficacy as assessed by the investigator

• Subject is receiving therapy with 1 of the following drugs, either concurrently or within 28 days prior to the Baseline Visit: alpha-methyl dopa, metoclopramide, reserpine, neuroleptics (except specific atypical neuroleptics: olanzapine, ziprasidone, aripiprazole, clozapine, and quetiapine), monoamine oxidase-A (MAO-A) inhibitors, methylphenidate, amphetamine, or other dopamine agonists (DAs)

• Subject is receiving central nervous system (CNS) therapy (eg, sedatives, hypnotics, selective serotonin reuptake inhibitors [SSRIs], anxiolytics, or other sleep-modifying medication) unless dose has been stable daily for at least 28 days prior to the Baseline Visit and is likely to remain stable for the duration of the study

• Subject has evidence of an impulse control disorder according to the modified Minnesota Impulsive Disorders Interview at the Screening Visit (Visit 1), confirmed by a positive structured clinical interview

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Idiopathic Parkinson's Disease
• Parkinson Disease

Intervention

Other:
• Placebo
Placebo patches of 2, 4, 6 & 8 mg / 24 hours Daily application of Placebo patches starting at 2 mg / 24 hours (early Parkinson's Disease (PD) patients) or 4 mg / 24 hours (advanced PD patients). Dose was up-titrated in weekly increments of 2 mg / 24 hours until optimal or maximal dose was reached. Maximal dose was 8 mg / 24 hours for early PD patients and 16 mg / 24 hours for advanced PD patients. Optimal or maximal dose was maintained for 12 weeks followed by a de-escalation by 2 mg / 24 hours every other day.

Drug:
• Rotigotine
Rotigotine patches of 2, 4, 6, and 8 mg / 24 hours Once daily application of Rotigotine patches starting at 2 mg / 24 hours (early Parkinson's Disease (PD) patients) or 4 mg / 24 hours (advanced PD patients). Dose was up-titrated in weekly increments of 2 mg / 24 hours until optimal or maximal dose was reached. Maximal dose is 8 mg / 24 hours for early PD patients and 16 mg / 24 hours for advanced PD patients. Optimal or maximal dose was maintained for 12 weeks followed by a de-escalation by 2 mg / 24 hours every other day.

Locations

Country	Name	City	State
Austria	101	Feldbach
Austria	104	Wien
Austria	107	Wien
Belgium	125	Antwerpen
Belgium	121	Brugge
Belgium	122	Brussels
Belgium	124	Gent
Belgium	131	Liege
Bulgaria	44	Plovdiv
Bulgaria	52	Russe
Bulgaria	41	Sofia
Bulgaria	45	Sofia
Bulgaria	48	Sofia
Bulgaria	49	Sofia
Bulgaria	53	Sofia
Bulgaria	42	Varna
Czech Republic	232	Chomutov
Czech Republic	227	Litomysl
Czech Republic	222	Ostrava-Poruba
Czech Republic	231	Plzen
Czech Republic	233	Praha
France	189	Aix-en Provence
France	181	Amiens
France	186	Limoges
France	185	Pessac
France	184	Roanne
France	183	Toulouse
Germany	62	Berlin
Germany	77	Berlin
Germany	80	Böblingen
Germany	67	Bochum
Germany	61	Marburg
Germany	79	Oldenburg
Germany	114	Stuttgart
Germany	65	Ulm
Germany	73	Westerstede
Hungary	87	Budapest
Hungary	88	Budapest
Hungary	95	Gyor
Hungary	89	Miskolc
Hungary	81	Nyiregyhaza
Hungary	84	Pecs
Hungary	86	Szeged
Italy	254	Arcugnano
Italy	267	Chieti Scalo
Italy	270	Napoli
Italy	266	Perugia
Italy	264	Pisa
Italy	257	Pozzilli
Italy	262	Roma
Italy	269	Treviso
Italy	258	Varese
Italy	252	Venezia
Italy	255	Verona
Romania	207	Brasov
Romania	201	Bucuresti
Romania	213	Bucuresti
Romania	203	Clluj-Napoca
Romania	211	Cluj-Napoca
Romania	208	Sibiu
Romania	217	Sibiu
Romania	212	Targu Mures
Romania	204	Timisoara
Romania	209	Timisoara
Slovakia	245	Banska Bystrica
Slovakia	247	Banska Bystrica
Slovakia	240	Bratislava
Slovakia	242	Bratislava
Slovakia	243	Bratislava
Slovakia	249	Dolni Kubin
Slovakia	250	Krompachy
Slovakia	244	Lucenec
Slovakia	248	Zilina
Spain	157	Alicante
Spain	142	Barcelona
Spain	146	Barcelona
Spain	143	Madrid
Spain	145	Madrid
Spain	147	Madrid
Spain	148	Madrid
Spain	158	Oviedo
Spain	141	Sant Cugat (Barcelona)
Spain	152	Santiago de Compostela
Switzerland	24	Lugano
Switzerland	26	Sargans
Switzerland	21	St. Gallen
Switzerland	22	Zuerich

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

Countries where clinical trial is conducted

Austria,  Belgium,  Bulgaria,  Czech Republic,  France,  Germany,  Hungary,  Italy,  Romania,  Slovakia,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to the End of Maintenance in Total Nonmotor Symptoms Scale (NMSS) Score	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in the following 9 domain categories: cardiovascular, including falls; sleep/fatigue; mood/cognition; perceptual problems/hallucinations; attention/memory; gastrointestinal tract; urinary; sexual function; miscellaneous. Severity and frequency are rated using a 4-point scale ranging from 0 (none) to 3 (severe; major source of distress or disturbance to subject) for severity and from 1 (rarely) to 4 (very frequent [daily or all the time]) for frequency. The total NMSS score ranges from 0 to 350. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in Total Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score	The Unified Parkinson's Disease Rating Scale (UPDRS) Part III is a scale for the assessment of function in Parkinson's Disease. UPDRS Part III measures Motor Function. It consists of 14 items with 27 questions, each ranging from 0 to 4. The sum score for the UPDRS Part III ranges from 0 to 108. A higher score indicates greater disability. A negative change from Baseline to end of Maintenance score indicates improvement.	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in Health-related Quality of Life (HRQL) Measured by a 39-item Parkinson's Disease Questionnaire (PDQ-39)	Parkinson's Disease Questionnaire - 39 (PDQ-39) is a self-administered questionnaire. It comprises of 39 questions, relating to eight key areas of health and daily activities, including both Motor and Non-motor symptoms. It is scored on a scale of zero to 100, with lower scores indicating better health and high scores more severe symptoms in change from Baseline to end of Maintenance.	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Cardiovascular	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.; The final score is derived from multiplying the severity score and the frequency score.; A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.; The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Cardiovascular (2 questions): range 0 - 24	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sleep/Fatigue	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.; The final score is derived from multiplying the severity score and the frequency score.; A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.; The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Sleep/Fatigue (4 questions): range 0-48	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Mood/Cognition	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.; The final score is derived from multiplying the severity score and the frequency score.; A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.; The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Mood/Cognition (6 questions): range 0 - 72	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Perception/Hallucinations	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.; The final score is derived from multiplying the severity score and the frequency score.; A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.; The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Perception/Hallucinations (3 questions): range 0 - 36	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Attention/Memory,	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.; The final score is derived from multiplying the severity score and the frequency score.; A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.; The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Attention/Memory (3 questions): range 0 - 36	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Gastrointestinal Tract	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.; The final score is derived from multiplying the severity score and the frequency score.; A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.; The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Gastrointestinal tract (3 questions): range 0 - 36	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Urinary	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.; The final score is derived from multiplying the severity score and the frequency score.; A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.; The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Urinary (3 questions): range 0 - 36	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sexual Function	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.; The final score is derived from multiplying the severity score and the frequency score.; A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.; The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Sexual function (2 questions): range 0 - 24	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No
Secondary	Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Miscellaneous	The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale.; The final score is derived from multiplying the severity score and the frequency score.; A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.; The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Miscellaneous (4 questions): range 0 - 48	From Baseline (Day 1) to end of 12-week Maintenance (Day 84)	No

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