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

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00474058
• Collaborator: (none)
• Enrollment: 287
• Locations: 47
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The objective of this trial is to assess the effects of transdermal rotigotine on the control of early morning motor function and sleep disorders compared to placebo in subjects with idiopathic Parkinsons´s disease. In addition, effects of rotigotine on specific nocturnal and non-motor symptoms of Parkinson´s disease will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Rotigotine; Other: Placebo	Phase 3

Detailed Description

The objective of this trial is to assess the effects of rotigotine on the control of early morning motor function and sleep disorders compared to placebo in subjects with idiopathic Parkinsons´s disease. In addition, effects of rotigotine on specific nocturnal and non-motor symptoms of Parkinson´s disease will be evaluated.

After a Screening Period of up to 28 days subjects will be hospitalized for two nights. After the second overnight stay, subjects will be randomly assigned either to rotigotine patch or placebo patch. Afterwards patients will be titrated to their optimal dose. After subjects have reached their optimal dose (or the highest dose) they will be maintained on this dose for a certain period. At the end of maintenance the subjects will be hospitalized for two nights. Afterwards the doses will be continuously decreased.

Efficacy will be assessed by application of sleep quality scores, motor examination scores, and scores to evaluate non-motor symptoms of Parkinsons. Safety assessments include adverse events, 12-lead electrocardiograms, blood pressure and heart rate assessments, and laboratory checks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 287 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 3B, Multicenter, Multinational, Double-Blind, Placebo Controlled, 2-Arm Trial to Evaluate the Effect of the 24-Hour Transdermal Delivery of Rotigotine on the Control of Early Morning Motor Function, Sleep Quality, Nocturnal Symptoms, and Non-Motor Symptoms in Subjects With Idiopathic Parkinson's Disease
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rotigotine Rotigotine transdermal patch	Drug: Rotigotine; Rotigotine transdermal patches: 10cm2 (2mg/24h); 20cm2 (4mg/24h); 30cm2 (6mg/24h); 40cm2 (8mg/24h) Optimal dosing: The maximum Rotigotine dose allowed is 16mg/24h; Other Names: Neupro
Placebo Comparator: Placebo Placebo transdermal patch	Other: Placebo; Placebo transdermal patches

Outcome Measures

Primary Outcome Measures

1. Change in Early Morning UPDRS Part III Score [From baseline to end of maintenance (after 4 weeks maintenance)]

   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.

2. Change in Parkinson's Disease Sleep Scale (PDSS) [From baseline to end of maintenance (after 4 weeks maintenance)]

   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.

Secondary Outcome Measures

1. Change in Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS) [From baseline to end of maintenance (after 4 weeks maintenance)]

   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.

2. Change in Number of Nocturias [From baseline to end of maintenance (after 4 weeks maintenance)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Early and advanced Idiopathic Parkinson Disease with early morning motor impairment

Exclusion Criteria:

• Atypical Parkinsonian syndromes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Reseda	California	United States
2		Ventura	California	United States
3		St. Petersburg	Florida	United States	33701
4		Salisbury	North Carolina	United States	28144
5		Winston_Salem	North Carolina	United States
6		Warwick	Rhode Island	United States
7		Houston	Texas	United States
8		Concord	New South Wales	Australia
9		Adelaide	South Australia	Australia
10		Fitzroy		Australia
11		Innsbruck		Austria	6020
12		Hyvinkää		Finland
13		Oulu		Finland	90220
14		Berlin		Germany	10713
15		Berlin		Germany	12163
16		Dresden		Germany	01307
17		Kassel		Germany	34128
18		Leipzig		Germany
19		Marburg		Germany	35039
20		Naumburg		Germany
21		Ulm		Germany	89081
22		Budapest		Hungary
23		Debrecen		Hungary
24		Nyiregyhaza		Hungary
25		Zalaegerszeg		Hungary
26		Chieti		Italy	66013
27		Milano		Italy
28		Torino		Italy
29		Christ Church		New Zealand
30		Wellington		New Zealand
31		Gdansk		Poland
32		Krakow		Poland
33		Lublin		Poland
34		Olsztyn		Poland
35		Szczecin		Poland
36		Warszawa		Poland
37		Cape Town		South Africa
38		Capetown		South Africa
39		Johannesburg		South Africa
40		Pretoria/Gauteng		South Africa
41		Tygerberg		South Africa
42		Barcelona		Spain	08036
43		Madrid		Spain
44		Bristol		United Kingdom
45		Lancashire		United Kingdom
46		Liverpool		United Kingdom
47		London		United Kingdom

Sponsors and Collaborators

• UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] (UCB)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00474058
• Other Study ID Numbers: SP0889; EudraCT No.: 2006-006752-35
• First Posted: May 16, 2007
• Last Update Posted: Jun 22, 2015
• Last Verified: May 1, 2015

• Keywords provided by UCB Pharma: rotigotine; Neupro®; Parkinson's Disease
• Additional relevant MeSH terms: Parkinson Disease; Rotigotine

Study Results

Participant Flow

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

Arm/Group Title	Rotigotine	Placebo
Arm/Group Description	Rotigotine transdermal patch	Placebo transdermal patch
Period Title: Overall Study
STARTED	190	97
COMPLETED	166	80
NOT COMPLETED	24	17

Baseline Characteristics

Arm/Group Title	Rotigotine	Placebo	Total
Arm/Group Description	Rotigotine transdermal patch	Placebo transdermal patch	Total of all reporting groups
Overall Participants	178	89	267
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	87 48.9%	40 44.9%	127 47.6%
>=65 years	91 51.1%	49 55.1%	140 52.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.7 (9.4)	64.5 (10.4)	64.6 (9.7)
Sex: Female, Male (Count of Participants)
Female	61 34.3%	31 34.8%	92 34.5%
Male	117 65.7%	58 65.2%	175 65.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.6%	1 1.1%	2 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 1.1%	1 1.1%	3 1.1%
White	164 92.1%	79 88.8%	243 91%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	11 6.2%	8 9%	19 7.1%
Body Mass Index (BMI) (kg/ m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/ m^2]	26.676 (4.164)	26.645 (4.569)	26.665 (4.295)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	169.04 (9.11)	170.73 (9.27)	169.60 (9.18)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	76.6 (15.1)	78.0 (16.2)	77.1 (15.5)

Outcome Measures

1. Primary Outcome

Title	Change in Early Morning UPDRS Part III Score
Description	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.
Time Frame	From baseline to end of maintenance (after 4 weeks maintenance)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rotigotine	Placebo
Arm/Group Description	Rotigotine transdermal patch	Placebo transdermal patch
Measure Participants	178	89
Mean (Standard Deviation) [units on a scale]	-7.0 (7.6)	-3.9 (7.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rotigotine, Placebo
	Comments	Analyses of covariance were performed for the efficacy variables with treatment and (pooled) sites as factors, and baseline value as covariate. Least square means (LS means) for treatment effect were calculated and differences between rotigotine and placebo were presented with 95% confidence intervals (CIs) and p- values.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	No p-value adjustment was necessary, since a multiple test procedure in a hierarchical sequentially rejective manner for the primary variable was applied.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.55
	Confidence Interval	() 95%; -5.37 to -1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change in Parkinson's Disease Sleep Scale (PDSS)
Description	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.
Time Frame	From baseline to end of maintenance (after 4 weeks maintenance)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rotigotine	Placebo
Arm/Group Description	Rotigotine transdermal patch	Placebo transdermal patch
Measure Participants	178	89
Mean (Standard Deviation) [units on a scale]	-5.9 (7.6)	-1.9 (8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rotigotine, Placebo
	Comments	Analyses of covariance were performed for the efficacy variables with treatment and (pooled) sites as factors, and baseline value as covariate. Least square means (LS means) for treatment effect were calculated and differences between rotigotine and placebo were presented with 95% confidence intervals (CIs) and p- values.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No p-value adjustment was necessary, since a multiple testing in a hierarchical sequentially rejective manner for the primary variable was applied.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.26
	Confidence Interval	() 95%; -6.08 to -2.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS)
Description	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.
Time Frame	From baseline to end of maintenance (after 4 weeks maintenance)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Rotigotine	Placebo
Arm/Group Description	Rotigotine transdermal patch	Placebo transdermal patch
Measure Participants	163	78
Mean (Standard Deviation) [units on a scale]	-1.3 (1.8)	-0.9 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rotigotine, Placebo
	Comments	Analyses of covariance were performed for the efficacy variables with treatment and (pooled) sites as factors, and baseline value as covariate. Least square means (LS means) for treatment effect were calculated and differences between rotigotine and placebo were presented with 95% confidence intervals (CIs) and p- values.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0301
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.41
	Confidence Interval	() 95%; -0.79 to -0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in Number of Nocturias
Description	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.
Time Frame	From baseline to end of maintenance (after 4 weeks maintenance)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Rotigotine	Placebo
Arm/Group Description	Rotigotine transdermal patch	Placebo transdermal patch
Measure Participants	161	78
Mean (Standard Deviation) [nocturias]	-0.3 (1.3)	-0.2 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rotigotine, Placebo
	Comments	Analyses of covariance were performed for the efficacy variables with treatment and (pooled) sites as factors, and baseline value as covariate. Least square means (LS means) for treatment effect were calculated and differences between rotigotine and placebo were presented with 95% confidence intervals (CIs) and p- values.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8842
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	() 95%; -0.29 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse Events (AEs) were collected up to 22 weeks from Visit 1 to the Safety Follow- Up Visit.
Adverse Event Reporting Description	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.
Arm/Group Title	Rotigotine		Placebo
Arm/Group Description	Rotigotine transdermal patch		Placebo transdermal patch
All Cause Mortality
	Rotigotine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rotigotine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/191 (5.2%)		5/96 (5.2%)
Gastrointestinal disorders
Diarrhoea	1/191 (0.5%)	1	0/96 (0%)	0
General disorders
Oedema peripheral	0/191 (0%)	0	1/96 (1%)	1
Hepatobiliary disorders
Cholecystitis	1/191 (0.5%)	1	0/96 (0%)	0
Infections and infestations
Urosepsis	1/191 (0.5%)	1	0/96 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/191 (0.5%)	2	0/96 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/191 (0.5%)	1	0/96 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukaemia	0/191 (0%)	0	1/96 (1%)	1
Basal cell carcinoma	0/191 (0%)	0	1/96 (1%)	1
Nervous system disorders
Cerebrovascular accident	0/191 (0%)	0	1/96 (1%)	1
Syncope	1/191 (0.5%)	1	0/96 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion	1/191 (0.5%)	1	0/96 (0%)	0
Psychiatric disorders
Panic attack	0/191 (0%)	0	1/96 (1%)	1
Completed suicide	0/191 (0%)	0	1/96 (1%)	1
Hallucination, visual	1/191 (0.5%)	1	0/96 (0%)	0
Sleep attacks	1/191 (0.5%)	1	0/96 (0%)	0
Renal and urinary disorders
Nephrotic syndrome	0/191 (0%)	0	1/96 (1%)	1
Renal impairment	0/191 (0%)	0	1/96 (1%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/191 (0.5%)	1	0/96 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	0/191 (0%)	0	1/96 (1%)	1
Other (Not Including Serious) Adverse Events
	Rotigotine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	70/191 (36.6%)		21/96 (21.9%)
Gastrointestinal disorders
Nausea	41/191 (21.5%)	54	9/96 (9.4%)	14
Nervous system disorders
Dizziness	20/191 (10.5%)	27	6/96 (6.3%)	6
Headache	13/191 (6.8%)	14	5/96 (5.2%)	5
Dyskinesia	15/191 (7.9%)	16	4/96 (4.2%)	4

Limitations/Caveats

During the course of the trial, the manufacturing process for rotigotine was changed. At that time, the expiry date for trial medication was Apr 2009, recruitment for SP889 had to be stopped effective on 17 Nov 2008.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

"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."