A Phase 3b, Open-Label, Safety and Efficacy Study of Rotigotine as Add-On Therapy With Low Doses of Pramipexole or Ropinirole in Patients With Advanced Parkinson's Disease

An Open-Label Study to Investigate the Safety and Efficacy of Rotigotine Add-On Therapy With Low Doses of Pramipexole or Ropinirole in Patients With Advanced Parkinson's Disease Phase 3B

This study is to investigate the safety and efficacy of Rotigotine add-on therapy with low doses of Pramipexole or Ropinirole in patients with advanced-stage Parkinson's Disease (PD) who have insufficient response to L-dopa and low doses dopamine receptor agonists.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Chatswood, New South Wales, Australia
      • 402
    • Sydney, New South Wales, Australia
      • 401
  • Victoria
    • Melbourne, Victoria, Australia
      • 403
• Korea, Republic of
  • Busan, Korea, Republic of
    • 104
  • Busan, Korea, Republic of
    • 112
  • Daegu, Korea, Republic of
    • 109
  • Gyeonggi-Do, Korea, Republic of
    • 111
  • Seoul, Korea, Republic of
    • 101
  • Seoul, Korea, Republic of
    • 102
  • Seoul, Korea, Republic of
    • 103
  • Seoul, Korea, Republic of
    • 105
  • Seoul, Korea, Republic of
    • 107
  • Seoul, Korea, Republic of
    • 108
  • Seoul, Korea, Republic of
    • 110
• Malaysia
  • Kuala Terengganu, Malaysia
    • 202
  • Kuching Sarawak, Malaysia
    • 204
  • Pulau Pinang, Malaysia
    • 201
• Singapore
  • Singapore, Singapore
    • 501
  • Singapore, Singapore
    • 502
• Taiwan
  • Taichung, Taiwan
    • 302
  • Tainan, Taiwan
    • 303
  • Taipei, Taiwan
    • 306

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is male or female, aged ≥ 30 and < 80 years at informed consent
• Subject has idiopathic Parkinson's Disease, of more than 3 years duration, as defined by the cardinal sign, bradykinesia, and the presence of at least 1 of the following: resting tremor, rigidity, impairment of postural reflexes, and without any known or suspected cause of Parkinsonism
• Subject has motor fluctuations such as wearing, dyskinesia
• Subject has experienced nocturias for at least 3 nights within 7 days prior to Baseline
• Subject is taking levodopa (L-DOPA, immediate and/or controlled release) in combination with benserazide or carbidopa and has been on a stable dose of L-DOPA for at least 28 days prior to Baseline (Visit 2)
• Subject is taking a non-ergot dopamine agonist (pramipexole ≤ 1.5 mg/day or ropinirole ≤ 6.0 mg/day) and has been on a stable dose of non-ergot dopamine agonist for at least 28 days prior to Baseline (Visit 2)

Exclusion Criteria:

• Subject is receiving therapy with tolcapone or budipine
• Subject is receiving therapy with one of the following drugs either concurrently or within 28 days prior to Baseline (Visit 2): 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 has a history of symptomatic (not asymptomatic) orthostatic hypotension within the 6 months prior to Baseline (Visit 2)
• Subject has a known hypersensitivity to any components of the study medication, such as a history of significant skin hypersensitivity to adhesives, known hypersensitivity to other transdermal medications, or has unresolved contact dermatitis
• Subject is pregnant or nursing, or is of child-bearing potential (ie, is (i) not surgically sterile, or, (ii) not using adequate birth control methods [including at least one barrier method] or, (iii) not sexually abstinent, or (iv) not at least 2 years post menopausal)
• Subject had a previous diagnosis of narcolepsy, sleep apnea syndrome, restless legs syndrome, or periodic limb movement disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rotigotine; - Titration Period: Weekly titration to the subject's optimal dose of Rotigotine between 2 mg/24 h and 8 mg/24 h. In case of intolerable Adverse Events (AEs) one back-titration is allowed during the Titration Period. Duration of the Titration Period: Between 1 week and 5 weeks. - Maintenance Period: Starts once subject reached either optimal or maximal dose of Rotigotine. Subjects receive stable dose of Rotigotine throughout the Maintenance Period. No back-titration is allowed during the Maintenance Period. Duration of the Maintenance Period: Between 3 weeks and 7 weeks.

Drug: Rotigotine; Application of Rotigotine up to 8 mg/24 h patches for 24 hours.; Other Names: Neupro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period	The CGI Item 4 was used to assess side effects. It ranges from 0 to 4 as follows: 0 = Side effects not assessable; = No side effects; = Side effects do not significantly interfere with subject's functioning; = Side effects significantly interfere with the subject's functioning; = Side effects outweigh therapeutic efficacy.	Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)
Change From Baseline to the End of the Treatment Period in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III ("on" State) Total Score	The Unified Parkinson´s Disease Rating Scale Part III is an accepted and validated scale for the assessment of motor function in Parkinson´s disease. Each of the 27 sub-items in the UPDRS III is measured on a scale of 0 to 4, where 0 is normal and 4 represents severe abnormalities. The total scores therefore ranges from 0 to 108. A negative value in Change from Baseline to Week 8 indicates an improvement in motor functions from Baseline.	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)
Change From Baseline to the End of the Treatment Period in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Average of "on" and "Off" State) Total Score	UPDRS Part II measures 'Activities in Daily Living'. The total score ranges from 0 (Best score possible) to 52 (Worst score possible). UPDRS Part II total score (average of "on" and "off" state) is the average of UPDRS Part II total score ("on" state) and Part II total score ("off" state). A negative value in Change from Baseline to Week 8 indicates an improvement in activities in daily living from Baseline.	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)
Change From Baseline to the End of the Treatment Period in Absolute Time Spent "Off"	Absolute time spent "off" is measured in hours per day. A negative value in Change from Baseline to Week 8 indicates that the time spent "off" decreased from Baseline and therefore indicates an improvement from Baseline. Only subjects with time spent "off" at Baseline (subset of the Full Analysis Set (FAS)) are included in the analysis of this outcome measure.	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to the End of the Treatment Period in Time Spent "on" Without Troublesome Dyskinesia	Absolute time spent "on" without troublesome dyskinesia is measured in hours per day. A positive value in Change from Baseline to Week 8 indicates that the time spent "on" without troublesome dyskinesia increased from Baseline and therefore indicates an improvement from Baseline.	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)
Change From Baseline to the End of Treatment Period in Parkinson's Disease Sleep Scale 2 (PDSS-2) Total Score	The Parkinson´s Disease Sleep Scale (PDSS) is a questionnaire with 15 questions to assess sleep disturbance and nocturnal disability in Parkinson´s disease. The item- scores can range between 0= never and 4= very often. The PDSS score is a sum score of all 15 questions. A negative value in Change from Baseline to Week 8 indicates an improvement from Baseline.	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)
Change From Baseline to the End of Treatment Period in the Pittsburgh Sleep Quality Index (PSQI) Global Score	The Pittsburgh Sleep Quality Index (PSQI) is a questionnaire with 18 questions to assess sleep quality. The 18 questions are distributed to 7 elements with each element ranging from 0-3. The global score is the sum score of all 7 elements and ranges from 0-21 with higher values indicating worse sleep quality. A negative value in Change from Baseline to Week 8 indicates an improvement in sleep quality from Baseline.	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES GmbH
• Collaborators: Otsuka Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Kim JM, Chung SJ, Kim JW, Jeon BS, Singh P, Thierfelder S, Ikeda J, Bauer L; Asia Pacific Rotigotine Add-on Study Group. Rotigotine transdermal system as add-on to oral dopamine agonist in advanced Parkinson's disease: an open-label study. BMC Neurol. 2015 Feb 28;15:17. doi: 10.1186/s12883-015-0267-7.

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: November 6, 2012
• First Submitted That Met QC Criteria: November 6, 2012
• First Posted (Estimate): November 8, 2012

Study Record Updates

• Last Update Posted (Estimate): June 3, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Rotigotine; Neupro
• 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: PD0015