An Open-Label Extension Trial to Assess the Safety of Long-Term Treatment of Rotigotine in Advanced-Stage Parkinson's Disease

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00501969
• Collaborator: (none)
• Enrollment: 395
• Locations: 53
• Arm: 1
• Duration (Months): 52
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The objective of this open-label extension is to assess the safety and tolerability of long-term treatment of the rotigotine patch in subjects with advanced-stage idiopathic Parkinson's disease

Condition or Disease	Intervention/Treatment	Phase
Advanced Stage Parkinson's Disease	Drug: Rotigotine	Phase 3

Detailed Description

This is the open-label extension to the randomized, double-blind, placebo-and active controlled SP515 (NCT00244387) trial that assessed the efficacy and safety and tolerability of the Rotigotine patch in subjects with advanced-stage idiopathic Parkinson's Disease that were not well-controlled on levodopa

Study Design

• Study Type: Interventional
• Actual Enrollment: 395 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Extension to the Double-Blind SP515 (NCT00244387) Trial to Assess the Safety of Long-Term Treatment of Rotigotine in Subjects With Advanced-Stage Idiopathic Parkinson's Disease Who Are Not Well Controlled on L-Dopa
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rotigotine Rotigotine	Drug: Rotigotine; Rotigotine trans-dermal patches once daily: 20 cm2 (4 mg/24 hours); 30 cm2 (6 mg/24 hours); 40 cm2 (8 mg/24 hours) 50 cm2 (10 mg/24 hours) 60 cm2 (12 mg/24 hours) 70 cm2 (14 mg/24 hours) 80 cm2 (16 mg/24 hours); Other Names: Neupro®

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With at Least One Adverse Event During This Open-label Extension Study [five years]

   Adverse events are any untoward medical occurrences in a subject administered study treatment, whether or not these events are related to treatment.

Secondary Outcome Measures

1. Number of Subjects Who Withdrew From the Trial Due to an Adverse Event [five years]

   Adverse events are any untoward medical occurrences in a subject administered study treatment, whether or not these events are related to treatment.

2. Mean Epworth Sleepiness Scale Score During the Open-label Extension [Visit 13 (end of year 1), Visit 17 (end of year 2), Visit 21 (end of year 3), Visit 25(end of year 4)]

   The Epworth Sleepiness Scale (ESS) is a self-administered questionnaire with 8 questions. The total ESS score is the sum of 8 item-scores and can range between 0 and 24. The higher the score, the higher the person's level of daytime sleepiness.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 31 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who have completed four months of maintenance treatment in the SP515 (NCT00244387) double-blind trial

Exclusion Criteria:

• Subjects who had an ongoing serious adverse event from SP515 (NCT00244387) double-blind trial that was assessed as related to study medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bedford Park		Australia
2		Concord		Australia
3		Darlinghurst		Australia
4		East Gosford		Australia
5		Westmead		Australia
6		Innsbruck		Austria
7		Zagreb		Croatia
8		Brno		Czech Republic
9		Ostrava - Poruba		Czech Republic
10		Pardubice		Czech Republic
11		Plzen		Czech Republic
12		Praha		Czech Republic
13		Oulu		Finland
14		Pori		Finland
15		Aix-en -Provence		France
16		Lille cedex		France
17		Lyon		France
18		Aachen		Germany
19		Bochum		Germany
20		Budapest		Hungary
21		Miskolc		Hungary
22		Pecs		Hungary
23		Petach-Tikva		Israel
24		Tel Aviv		Israel
25		Milano		Italy
26		Napoli		Italy
27		Padova		Italy
28		Pisa		Italy
29		Pozzilli		Italy
30		Roma		Italy
31		Auckland		New Zealand
32		Christchurch		New Zealand
33		Wellington		New Zealand
34		Bergen		Norway
35		Stavanger		Norway
36		Tonsberg		Norway
37		Trondheim		Norway
38		Gdansk		Poland
39		Krakow		Poland
40		Lublin		Poland
41		Mosina k/Poznania		Poland
42		Olsztyn		Poland
43		Warszawa		Poland
44		Cape Town		South Africa
45		Pretoria		South Africa
46		Tygerberg		South Africa
47		Barcelona		Spain
48		Madrid		Spain
49		San Sebastian		Spain
50		Stockholm		Sweden
51		Blackpool		United Kingdom
52		Glasgow		United Kingdom
53		Sheffield		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: NCT00501969
• Other Study ID Numbers: SP0516; 2004-000148-26
• First Posted: Jul 17, 2007
• Last Update Posted: Oct 2, 2014
• Last Verified: Mar 1, 2012

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

Study Results

Participant Flow

Recruitment Details	An Open-Label Extension to the Double-Blind SP515 (NCT00244387) Trial to Assess the Safety of Long-Term Treatment of Rotigotine in Subjects with Advanced-Stage Idiopathic Parkinson's Disease who are not well controlled on L-Dopa from August 2004 to December 2008

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Subjects can receive a dose up to 16 mg/24 hours.
Period Title: Overall Study
STARTED	395
COMPLETED	189
NOT COMPLETED	206

Baseline Characteristics

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Subjects can receive a dose up to 16 mg/24 hours.
Overall Participants	395
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	183 46.3%
>=65 years	212 53.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.4 (9.2)
Sex: Female, Male (Count of Participants)
Female	144 36.5%
Male	251 63.5%
Region of Enrollment (participants) [Number]
Finland	8 2%
Spain	35 8.9%
Austria	6 1.5%
Israel	22 5.6%
United Kingdom	10 2.5%
Italy	33 8.4%
France	9 2.3%
Czech Republic	50 12.7%
Hungary	11 2.8%
Poland	65 16.5%
Croatia	27 6.8%
Australia	30 7.6%
South Africa	52 13.2%
Germany	4 1%
Norway	8 2%
New Zealand	16 4.1%
Sweden	9 2.3%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With at Least One Adverse Event During This Open-label Extension Study
Description	Adverse events are any untoward medical occurrences in a subject administered study treatment, whether or not these events are related to treatment.
Time Frame	five years

Outcome Measure Data

Analysis Population Description

Of the 395 subjects who entered the study, 395 are included in this summary based on the Safety Set (SS).

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Subjects can receive a dose up to 16 mg/24 hours.
Measure Participants	395
Number [Subjects]	357

2. Secondary Outcome

Title	Number of Subjects Who Withdrew From the Trial Due to an Adverse Event
Description	Adverse events are any untoward medical occurrences in a subject administered study treatment, whether or not these events are related to treatment.
Time Frame	five years

Outcome Measure Data

Analysis Population Description

Of the 395 subjects who entered the study, 395 are included in this summary based on the Safety Set (SS).

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Subjects can receive a dose up to 16 mg/24 hours.
Measure Participants	395
Number [Subjects]	76

3. Secondary Outcome

Title	Mean Epworth Sleepiness Scale Score During the Open-label Extension
Description	The Epworth Sleepiness Scale (ESS) is a self-administered questionnaire with 8 questions. The total ESS score is the sum of 8 item-scores and can range between 0 and 24. The higher the score, the higher the person's level of daytime sleepiness.
Time Frame	Visit 13 (end of year 1), Visit 17 (end of year 2), Visit 21 (end of year 3), Visit 25(end of year 4)

Outcome Measure Data

Analysis Population Description

Of the 395 subjects who entered the study, 395 are included in this summary based on the Safety Set (SS). Last observation carried forward (LOCF) was utilized.

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Subjects can receive a dose up to 16 mg/24 hours.
Measure Participants	395
Visit 13 (end of year 1) (n=377)	7.4 (4.7)
Visit 17 (end of year 2) (n=377)	7.8 (5.1)
Visit 21 (end of year 3) (n=377)	8.0 (5.1)
Visit 25 (end of year 4) (n=377)	8.3 (5.2)

Adverse Events

Time Frame	Up to five years
Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Subjects can receive a dose up to 16 mg/24 hours.
All Cause Mortality
	Rotigotine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rotigotine
	Affected / at Risk (%)	# Events
Total	148/395 (37.5%)
Blood and lymphatic system disorders
Anaemia	2/395 (0.5%)	2
Haemorrhagic anaemia	1/395 (0.3%)	1
Cardiac disorders
Myocardial infarction	3/395 (0.8%)	3
Myocardial ischaemia	2/395 (0.5%)	2
Angina pectoris	1/395 (0.3%)	1
Cardiac failure	4/395 (1%)	4
Sick sinus syndrome	2/395 (0.5%)	2
Atrial fibrillation	2/395 (0.5%)	2
Coronary artery disease	3/395 (0.8%)	3
Cardiac arrest	1/395 (0.3%)	1
Ischaemic cardiomyopathy	1/395 (0.3%)	1
Ear and labyrinth disorders
Vertigo positional	1/395 (0.3%)	1
Endocrine disorders
Toxic nodular goitre	1/395 (0.3%)	1
Eye disorders
Keratoconus	1/395 (0.3%)	1
Maculopathy	1/395 (0.3%)	1
Gastrointestinal disorders
Inguinal hernia	2/395 (0.5%)	2
Gastric perforation	1/395 (0.3%)	1
Gastric ulcer haemorrhage	1/395 (0.3%)	1
Rectal prolapse	1/395 (0.3%)	1
Gastric polyps	1/395 (0.3%)	1
Periodontitis	1/395 (0.3%)	1
Dysphagia	1/395 (0.3%)	1
Intestinal obstruction	1/395 (0.3%)	1
Haemorrhoids	1/395 (0.3%)	1
Gastrointestinal haemorrhage	1/395 (0.3%)	1
Small intestinal obstruction	1/395 (0.3%)	1
Duodenal ulcer haemorrhage	1/395 (0.3%)	1
Diarrhoea	1/395 (0.3%)	1
Vomiting	1/395 (0.3%)	1
General disorders
Chest pain	3/395 (0.8%)	3
Application site reaction	2/395 (0.5%)	2
Gait disturbance	2/395 (0.5%)	2
Unevaluable event	1/395 (0.3%)	1
Pyrexia	1/395 (0.3%)	1
Hernia	1/395 (0.3%)	1
Implant site haematoma	1/395 (0.3%)	1
Hepatobiliary disorders
Cholelithiasis	1/395 (0.3%)	1
Cholangitis	1/395 (0.3%)	1
Immune system disorders
Transplant rejection	1/395 (0.3%)	1
Infections and infestations
Pneumonia	7/395 (1.8%)	8
Bronchitis acute	1/395 (0.3%)	1
Lobar pneumonia	1/395 (0.3%)	1
Urinary tract infection	5/395 (1.3%)	5
Cellulitis	3/395 (0.8%)	3
Arthritis infective	1/395 (0.3%)	1
Intervertebral discitis	1/395 (0.3%)	1
Gastroenteritis	1/395 (0.3%)	1
Sepsis	1/395 (0.3%)	1
Gastroenteritis viral	1/395 (0.3%)	1
Lower respiratory tract infection viral	1/395 (0.3%)	1
Erysipelas	1/395 (0.3%)	1
Abscess	1/395 (0.3%)	1
Injury, poisoning and procedural complications
Femoral neck fracture	3/395 (0.8%)	3
Hip fracture	2/395 (0.5%)	2
Femur fracture	2/395 (0.5%)	2
Patella fracture	1/395 (0.3%)	1
Tibia fracture	1/395 (0.3%)	1
Fall	4/395 (1%)	4
Wound	1/395 (0.3%)	1
Road traffic accident	1/395 (0.3%)	1
Radius fracture	2/395 (0.5%)	2
Upper limb fracture	1/395 (0.3%)	1
Forearm fracture	1/395 (0.3%)	1
Joint dislocation	1/395 (0.3%)	1
Traumatic fracture	1/395 (0.3%)	1
Comminuted fracture	1/395 (0.3%)	1
Joint injury	1/395 (0.3%)	1
Meniscus lesion	1/395 (0.3%)	1
Concussion	1/395 (0.3%)	1
Narcotic intoxication	1/395 (0.3%)	1
Head injury	1/395 (0.3%)	1
Skin laceration	1/395 (0.3%)	1
Overdose	1/395 (0.3%)	1
Post procedural complication	1/395 (0.3%)	1
Pelvic fracture	1/395 (0.3%)	1
Skull fracture	1/395 (0.3%)	1
Spinal compression fracture	1/395 (0.3%)	1
Tendon rupture	1/395 (0.3%)	1
Investigations
Hepatic enzyme increased	1/395 (0.3%)	1
Metabolism and nutrition disorders
Diabetes mellitus non-insulin-dependent	1/395 (0.3%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis	4/395 (1%)	5
Spinal osteoarthritis	1/395 (0.3%)	1
Arthralgia	4/395 (1%)	4
Back pain	2/395 (0.5%)	2
Pain in extremity	1/395 (0.3%)	1
Arthropathy	2/395 (0.5%)	2
Bursa disorder	1/395 (0.3%)	1
Synovitis	1/395 (0.3%)	1
Rheumatoid arthritis	1/395 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	2/395 (0.5%)	2
Bronchial carcinoma	2/395 (0.5%)	2
Squamous cell carcinoma	1/395 (0.3%)	1
Metastatic neoplasm	1/395 (0.3%)	1
Malignant neoplasm of spinal cord	1/395 (0.3%)	1
Non-Hodgkin's lymphoma	1/395 (0.3%)	1
Colon neoplasm	1/395 (0.3%)	1
Lung neoplasm	1/395 (0.3%)	1
B-cell lymphoma	1/395 (0.3%)	1
Bladder neoplasm	1/395 (0.3%)	1
Nervous system disorders
Parkinson's disease	18/395 (4.6%)	22
Parkinsonism	4/395 (1%)	5
Cerebral haemorrhage	3/395 (0.8%)	3
Cerebrovascular accident	2/395 (0.5%)	2
Subarachnoid haemorrhage	1/395 (0.3%)	1
Syncope	3/395 (0.8%)	3
Loss of consciousness	2/395 (0.5%)	2
Radicular pain	1/395 (0.3%)	1
Cauda equina syndrome	1/395 (0.3%)	1
Dyskinesia	2/395 (0.5%)	2
Transient ischaemic attack	2/395 (0.5%)	2
Sciatica	2/395 (0.5%)	4
Dementia	1/395 (0.3%)	1
Monoparesis	1/395 (0.3%)	1
Neuropathy peripheral	1/395 (0.3%)	1
Tremor	1/395 (0.3%)	1
Convulsion	1/395 (0.3%)	1
Sudden onset of sleep	1/395 (0.3%)	1
Dysphasia	1/395 (0.3%)	1
Psychiatric disorders
Hallucination	4/395 (1%)	4
Hallucination, visual	4/395 (1%)	4
Delirium	2/395 (0.5%)	2
Obsessive-compulsive disorder	1/395 (0.3%)	1
Sleep attacks	1/395 (0.3%)	1
Delusional disorder, persecutory type	1/395 (0.3%)	1
Major depression	1/395 (0.3%)	1
Pathological gambling	1/395 (0.3%)	2
Psychotic disorder	1/395 (0.3%)	1
Suicidal ideation	1/395 (0.3%)	1
Renal and urinary disorders
Urinary retention	6/395 (1.5%)	7
Haematuria	3/395 (0.8%)	3
Nephrolithiasis	1/395 (0.3%)	1
Bladder disorder	1/395 (0.3%)	1
Renal colic	1/395 (0.3%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	3/395 (0.8%)	3
Cystocele	1/395 (0.3%)	1
Uterine prolapse	1/395 (0.3%)	1
Prostatism	1/395 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	2/395 (0.5%)	4
Asthma	1/395 (0.3%)	1
Pulmonary embolism	3/395 (0.8%)	3
Dyspnoea	1/395 (0.3%)	1
Pneumonia aspiration	1/395 (0.3%)	1
Respiratory failure	1/395 (0.3%)	1
Surgical and medical procedures
Deep brain stimulation	3/395 (0.8%)	3
Knee arthroplasty	3/395 (0.8%)	3
Drug therapy changed	1/395 (0.3%)	1
Rehabilitation therapy	1/395 (0.3%)	1
Cataract operation	1/395 (0.3%)	1
Spinal operation	1/395 (0.3%)	1
Open reduction of fracture	1/395 (0.3%)	1
Vascular disorders
Deep vein thrombosis	3/395 (0.8%)	3
Thrombophlebitis	1/395 (0.3%)	1
Orthostatic hypotension	1/395 (0.3%)	1
Cardiovascular insufficiency	1/395 (0.3%)	2
Haematoma	1/395 (0.3%)	1
Hypertension	1/395 (0.3%)	1
Circulatory collapse	1/395 (0.3%)	2
Aortic aneurysm	1/395 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Rotigotine
	Affected / at Risk (%)	# Events
Total	305/395 (77.2%)
Gastrointestinal disorders
Nausea	54/395 (13.7%)	62
Constipation	26/395 (6.6%)	29
General disorders
Application site erythema	40/395 (10.1%)	45
Application site pruritus	38/395 (9.6%)	39
Application site reaction	29/395 (7.3%)	32
Oedema peripheral	33/395 (8.4%)	35
Infections and infestations
Urinary tract infection	27/395 (6.8%)	46
Injury, poisoning and procedural complications
Fall	61/395 (15.4%)	117
Investigations
Weight decreased	43/395 (10.9%)	52
Weight increased	30/395 (7.6%)	32
Musculoskeletal and connective tissue disorders
Back pain	48/395 (12.2%)	57
Arthralgia	32/395 (8.1%)	36
Nervous system disorders
Somnolence	133/395 (33.7%)	170
Dyskinesia	55/395 (13.9%)	74
Parkinson's disease	44/395 (11.1%)	52
Dizziness	27/395 (6.8%)	31
Headache	27/395 (6.8%)	33
Psychiatric disorders
Hallucination	32/395 (8.1%)	35
Hallucination, visual	20/395 (5.1%)	27
Insomnia	45/395 (11.4%)	52
Depression	31/395 (7.8%)	33
Abnormal dreams	20/395 (5.1%)	23
Vascular disorders
Orthostatic hypotension	20/395 (5.1%)	21
Hypertension	24/395 (6.1%)	26

Limitations/Caveats

[Not Specified]

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 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.