Trial Outcomes & Findings for 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 (NCT NCT01723904)
NCT ID: NCT01723904
Last Updated: 2014-06-03
Results Overview
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.
COMPLETED
PHASE3
90 participants
Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)
2014-06-03
Participant Flow
This multicenter study started to enroll subjects in 5 countries in October 2012.
Participant Flow refers to the Safety Set (SS). SS consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
Participant milestones
| Measure |
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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
|
|---|---|
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Overall Study
STARTED
|
90
|
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Overall Study
COMPLETED
|
79
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
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Overall Study
Noncompliant
|
3
|
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Overall Study
Adverse Event
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5
|
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Overall Study
Unable to follow protocol/ judged by inv
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3
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Rotigotine
n=90 Participants
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
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Age, Continuous
|
61.3 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
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Age, Customized
< 65 years
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57 participants
n=5 Participants
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Age, Customized
>= 65 years
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33 participants
n=5 Participants
|
|
Sex: Female, Male
Female
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43 Participants
n=5 Participants
|
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Sex: Female, Male
Male
|
47 Participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
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8 participants
n=5 Participants
|
|
Region of Enrollment
Malaysia
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6 participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
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66 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)Population: From the 90 subjects in the Safatey Set, 89 are included in the analysis of this outcome measure. Last Observation Carried Forward (LOCF) was used as a method of imputation for missing observations.
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.
Outcome measures
| Measure |
Rotigotine
n=89 Participants
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
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Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period
CGI Item 4 score of 1
|
61 participants
|
|
Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period
CGI Item 4 score of 2
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22 participants
|
|
Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period
CGI Item 4 score of 3
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3 participants
|
|
Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period
CGI Item 4 score of 4
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3 participants
|
|
Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period
CGI Item 4 score of 3 or 4
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6 participants
|
PRIMARY outcome
Timeframe: From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) as a method of imputation for missing observations. FAS includes all subjects with at least 1 patch application during Treatment Period, and with an evaluable UPDRS Part III total score at Baseline and at least 1 valid value after Baseline to Day 64.
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.
Outcome measures
| Measure |
Rotigotine
n=89 Participants
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
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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
|
-5.3 units on a scale
Standard Deviation 8.3
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PRIMARY outcome
Timeframe: From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) as a method of imputation for missing observations. FAS includes all subjects with at least 1 patch application during Treatment Period, and with an evaluable UPDRS Part III total score at Baseline and at least 1 valid value after Baseline to Day 64.
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.
Outcome measures
| Measure |
Rotigotine
n=85 Participants
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
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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
|
-1.5 units on a scale
Standard Deviation 3.8
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PRIMARY outcome
Timeframe: From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)Population: Subjects with time spent "off" at Baseline in the FAS with Last Observation Carried Forward (LOCF) as a method of imputation for missing observations. FAS includes all subjects with at least 1 patch application during Treatment Period, and with an evaluable UPDRS Part III total score at Baseline and at least 1 valid value after Baseline to Day 64.
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.
Outcome measures
| Measure |
Rotigotine
n=80 Participants
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
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Change From Baseline to the End of the Treatment Period in Absolute Time Spent "Off"
|
-2.1 hours/day
Standard Deviation 2.9
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SECONDARY outcome
Timeframe: From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) as a method of imputation for missing observations. FAS includes all subjects with at least 1 patch application during Treatment Period, and with an evaluable UPDRS Part III total score at Baseline and at least 1 valid value after Baseline to Day 64.
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.
Outcome measures
| Measure |
Rotigotine
n=84 Participants
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
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Change From Baseline to the End of the Treatment Period in Time Spent "on" Without Troublesome Dyskinesia
|
1.9 hours/day
Standard Deviation 3.1
|
SECONDARY outcome
Timeframe: From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) as a method of imputation for missing observations. FAS includes all subjects with at least 1 patch application during Treatment Period, and with an evaluable UPDRS Part III total score at Baseline and at least 1 valid value after Baseline to Day 64.
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.
Outcome measures
| Measure |
Rotigotine
n=89 Participants
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
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Change From Baseline to the End of Treatment Period in Parkinson's Disease Sleep Scale 2 (PDSS-2) Total Score
|
-3.2 units on a scale
Standard Deviation 7.5
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SECONDARY outcome
Timeframe: From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period)Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) as a method of imputation for missing observations. FAS includes all subjects with at least 1 patch application during Treatment Period, and with an evaluable UPDRS Part III total score at Baseline and at least 1 valid value after Baseline to Day 64.
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.
Outcome measures
| Measure |
Rotigotine
n=89 Participants
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
|
Change From Baseline to the End of Treatment Period in the Pittsburgh Sleep Quality Index (PSQI) Global Score
|
-0.7 units on a scale
Standard Deviation 3.0
|
Adverse Events
Rotigotine
Serious adverse events
| Measure |
Rotigotine
n=90 participants at risk
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
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Injury, poisoning and procedural complications
Subdural haemorrhage
|
1.1%
1/90 • Number of events 1 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Nasopharyngeal cancer
|
1.1%
1/90 • Number of events 1 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
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Psychiatric disorders
Confusional state
|
1.1%
1/90 • Number of events 1 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
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Psychiatric disorders
Delirium
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1.1%
1/90 • Number of events 1 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
|
Psychiatric disorders
Hallucination
|
1.1%
1/90 • Number of events 1 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
|
Renal and urinary disorders
Urinary retention
|
1.1%
1/90 • Number of events 1 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
Other adverse events
| Measure |
Rotigotine
n=90 participants at risk
\- 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.
Rotigotine: Application of Rotigotine up to 8 mg/24 h patches for 24 hours.
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|---|---|
|
Gastrointestinal disorders
Nausea
|
7.8%
7/90 • Number of events 9 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
|
General disorders
Application site pruritus
|
13.3%
12/90 • Number of events 12 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
|
Infections and infestations
Nasopharyngitis
|
5.6%
5/90 • Number of events 5 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
|
Nervous system disorders
Dizziness
|
10.0%
9/90 • Number of events 11 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
|
Nervous system disorders
Dyskinesia
|
7.8%
7/90 • Number of events 7 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
|
Vascular disorders
Orthostatic hypotension
|
10.0%
9/90 • Number of events 11 • Adverse Events (AEs) were collected over the whole study duration from the Screening Period (Day -28 to Day -7) to the Safety Follow-up Visit (up to Day 78).
Adverse Events refer to the Saftey Set. Safety Set consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
|
Additional Information
UCB Clinical Trial Call Center
UCB
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60