Trial Outcomes & Findings for Randomized Evaluation of the 24-Hour Coverage: Efficacy of Rotigotine (NCT NCT00474058)

Last Updated: 2015-06-22

Results Overview

The Unified Parkinson´s Disease Rating Scale Part III score is an accepted and validated sumscore of 14 items for the assessment of motor function in Parkinson´s disease. Each of the 14 items in the UPDRS part III is measured on a scale of 0 to 4, where 0 is normal and 4 represents severe abnormalities.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

287 participants

Primary outcome timeframe

From baseline to end of maintenance (after 4 weeks maintenance)

Results posted on

2015-06-22

Participant Flow

A total of 333 subjects were enrolled in this trial and comprised the Enrolled Set (ES). 287 subjects were randomized and all of them received at least 1 dose of trial medication, so they all belong to the Safety Set (SS). 267 subjects belong to the Full Analysis Set (FAS).

Participant Flow shows all 287 subjects who has been enrolled and randomized. Baseline Characteristics are described for the Full Analysis Set (FAS).

Participant milestones

Participant milestones
Measure	Rotigotine Rotigotine transdermal patch	Placebo Placebo transdermal patch
Overall Study STARTED	190	97
Overall Study COMPLETED	166	80
Overall Study NOT COMPLETED	24	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Rotigotine Rotigotine transdermal patch	Placebo Placebo transdermal patch
Overall Study Adverse Event	11	6
Overall Study Lack of Efficacy	0	4
Overall Study Withdrawal by Subject	11	7
Overall Study Other	2	0

Baseline Characteristics

Randomized Evaluation of the 24-Hour Coverage: Efficacy of Rotigotine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rotigotine n=178 Participants Rotigotine transdermal patch	Placebo n=89 Participants Placebo transdermal patch	Total n=267 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	87 Participants n=5 Participants	40 Participants n=7 Participants	127 Participants n=5 Participants
Age, Categorical >=65 years	91 Participants n=5 Participants	49 Participants n=7 Participants	140 Participants n=5 Participants
Age, Continuous	64.7 years STANDARD_DEVIATION 9.4 • n=5 Participants	64.5 years STANDARD_DEVIATION 10.4 • n=7 Participants	64.6 years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	31 Participants n=7 Participants	92 Participants n=5 Participants
Sex: Female, Male Male	117 Participants n=5 Participants	58 Participants n=7 Participants	175 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	164 Participants n=5 Participants	79 Participants n=7 Participants	243 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Body Mass Index (BMI)	26.676 kg/ m^2 STANDARD_DEVIATION 4.164 • n=5 Participants	26.645 kg/ m^2 STANDARD_DEVIATION 4.569 • n=7 Participants	26.665 kg/ m^2 STANDARD_DEVIATION 4.295 • n=5 Participants
Height	169.04 cm STANDARD_DEVIATION 9.11 • n=5 Participants	170.73 cm STANDARD_DEVIATION 9.27 • n=7 Participants	169.60 cm STANDARD_DEVIATION 9.18 • n=5 Participants
Weight	76.6 kg STANDARD_DEVIATION 15.1 • n=5 Participants	78.0 kg STANDARD_DEVIATION 16.2 • n=7 Participants	77.1 kg STANDARD_DEVIATION 15.5 • n=5 Participants

PRIMARY outcome

Timeframe: From baseline to end of maintenance (after 4 weeks maintenance)

Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF).

Outcome measures

Outcome measures
Measure	Rotigotine n=178 Participants Rotigotine transdermal patch	Placebo n=89 Participants Placebo transdermal patch
Change in Early Morning UPDRS Part III Score	-7.0 units on a scale Standard Deviation 7.6	-3.9 units on a scale Standard Deviation 7.3

PRIMARY outcome

Timeframe: From baseline to end of maintenance (after 4 weeks maintenance)

Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF).

The Parkinson´s Disease Sleep Scale (PDSS) is a questionnaire with 15 questions to assess sleep and nocturnal disability in Parkinson´s disease. The item- scores can range between 0= never and 4= very often. The PDSS score is a sumscore of all 15 questions.

Outcome measures

Outcome measures
Measure	Rotigotine n=178 Participants Rotigotine transdermal patch	Placebo n=89 Participants Placebo transdermal patch
Change in Parkinson's Disease Sleep Scale (PDSS)	-5.9 units on a scale Standard Deviation 7.6	-1.9 units on a scale Standard Deviation 8.2

SECONDARY outcome

Timeframe: From baseline to end of maintenance (after 4 weeks maintenance)

Population: Full Analysis Set (FAS).

Subjects were asked to assess nocturnal akinesia, dystonia and cramps, using an ordinal severity scale. While a score of 0= normal and 4= maximal severity, subjects could also rate their symptoms with values of 0.5, 1.5, 2.5, 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps scores were used to evaluate sleep.

Outcome measures

Outcome measures
Measure	Rotigotine n=163 Participants Rotigotine transdermal patch	Placebo n=78 Participants Placebo transdermal patch
Change in Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS)	-1.3 units on a scale Standard Deviation 1.8	-0.9 units on a scale Standard Deviation 2.1

SECONDARY outcome

Timeframe: From baseline to end of maintenance (after 4 weeks maintenance)

Population: Full Analysis Set (FAS).

Nocturia is the need to get up during the night and interrupt sleep in order to urinate. It is a typical nocturnal symptom of Parkinson´s disease. The change from baseline in number of nocturias was used to evaluate improvements in sleep disorders.

Outcome measures

Outcome measures
Measure	Rotigotine n=161 Participants Rotigotine transdermal patch	Placebo n=78 Participants Placebo transdermal patch
Change in Number of Nocturias	-0.3 nocturias Standard Deviation 1.3	-0.2 nocturias Standard Deviation 1.1

Adverse Events

Rotigotine

Serious events: 10 serious events

Other events: 70 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Rotigotine n=191 participants at risk Rotigotine transdermal patch	Placebo n=96 participants at risk Placebo transdermal patch
Gastrointestinal disorders Nausea	21.5% 41/191 • Number of events 54 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	9.4% 9/96 • Number of events 14 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Nervous system disorders Dizziness	10.5% 20/191 • Number of events 27 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	6.2% 6/96 • Number of events 6 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Nervous system disorders Headache	6.8% 13/191 • Number of events 14 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	5.2% 5/96 • Number of events 5 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Nervous system disorders Dyskinesia	7.9% 15/191 • Number of events 16 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	4.2% 4/96 • Number of events 4 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.

Additional Information

UCB Clinical Trial Call Center

UCB

Phone: +1877 822 9493

Results disclosure agreements

Principal investigator is a sponsor employee "UCB has \> 60 days but \<= 180 days to review results communications prior to public release and may delete information that is confidential and compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome."
Publication restrictions are in place

Restriction type: OTHER

Measure	Rotigotine n=191 participants at risk Rotigotine transdermal patch	Placebo n=96 participants at risk Placebo transdermal patch
Nervous system disorders Syncope	0.52% 1/191 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Psychiatric disorders Panic attack	0.00% 0/191 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	1.0% 1/96 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Psychiatric disorders Completed suicide	0.00% 0/191 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	1.0% 1/96 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Pregnancy, puerperium and perinatal conditions Abortion	0.52% 1/191 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Psychiatric disorders Hallucination, visual	0.52% 1/191 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Gastrointestinal disorders Diarrhoea	0.52% 1/191 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
General disorders Oedema peripheral	0.00% 0/191 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	1.0% 1/96 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Hepatobiliary disorders Cholecystitis	0.52% 1/191 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Infections and infestations Urosepsis	0.52% 1/191 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Injury, poisoning and procedural complications Ankle fracture	0.52% 1/191 • Number of events 2 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.52% 1/191 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.00% 0/191 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	1.0% 1/96 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/191 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	1.0% 1/96 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Nervous system disorders Cerebrovascular accident	0.00% 0/191 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	1.0% 1/96 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Psychiatric disorders Sleep attacks	0.52% 1/191 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Renal and urinary disorders Nephrotic syndrome	0.00% 0/191 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	1.0% 1/96 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Renal and urinary disorders Renal impairment	0.00% 0/191 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	1.0% 1/96 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.52% 1/191 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	0.00% 0/96 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/191 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.	1.0% 1/96 • Number of events 1 • Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit. Serious and non- serious Adverse Events (AEs) refer to the Safety Set (SS). The SS includes all subjects who are randomized and received at least one dose of trial medication.