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

Phase 3

Completed

Conditions: Advanced Parkinson's Disease

Interventions: Drug: Rotigotine

Registration Number: NCT01723904

Lead Sponsor: UCB BIOSCIENCES GmbH

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 90

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rotigotine	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.

Primary Outcome Measures

Name	Time	Method
Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period	Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)	The CGI Item 4 was used to assess side effects. It ranges from 0 to 4 as follows: 0 = Side effects not assessable 1. = No side effects 2. = Side effects do not significantly interfere with subject's functioning 3. = Side effects significantly interfere with the subject's functioning 4. = Side effects outweigh therapeutic efficacy.
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	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)	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.
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	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)	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.
Change From Baseline to the End of the Treatment Period in Absolute Time Spent "Off"	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to the End of the Treatment Period in Time Spent "on" Without Troublesome Dyskinesia	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)	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.
Change From Baseline to the End of Treatment Period in Parkinson's Disease Sleep Scale 2 (PDSS-2) Total Score	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)	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.
Change From Baseline to the End of Treatment Period in the Pittsburgh Sleep Quality Index (PSQI) Global Score	From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)	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.

Trial Locations

Locations (22): 402
🇦🇺
Chatswood, New South Wales, Australia
112
🇰🇷
Busan, Korea, Republic of
101
🇰🇷
Seoul, Korea, Republic of
302
🇨🇳
Taichung, Taiwan
103
🇰🇷
Seoul, Korea, Republic of
201
🇲🇾
Pulau Pinang, Malaysia
502
🇸🇬
Singapore, Singapore
109
🇰🇷
Daegu, Korea, Republic of
105
🇰🇷
Seoul, Korea, Republic of
107
🇰🇷
Seoul, Korea, Republic of
204
🇲🇾
Kuching Sarawak, Malaysia
111
🇰🇷
Gyeonggi-Do, Korea, Republic of
102
🇰🇷
Seoul, Korea, Republic of
110
🇰🇷
Seoul, Korea, Republic of
104
🇰🇷
Busan, Korea, Republic of
401
🇦🇺
Sydney, New South Wales, Australia
108
🇰🇷
Seoul, Korea, Republic of
501
🇸🇬
Singapore, Singapore
303
🇨🇳
Tainan, Taiwan
306
🇨🇳
Taipei, Taiwan
202
🇲🇾
Kuala Terengganu, Malaysia
403
🇦🇺
Melbourne, Victoria, Australia