SP512OL: An Open-Label Extension Trial to Assess the Safety of Long-Term Treatment of Rotigotine in Early-Stage Parkinson's Disease.

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00594165
• Collaborator: (none)
• Enrollment: 217
• Locations: 42
• Arm: 1
• Duration (Months): 77
• Patients Per Site: 5.2
• 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 early-stage idiopathic Parkinson's disease.

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

Detailed Description

This is the open-label extension to the randomized, double-blind, placebo-controlled SP512 trial that assessed the efficacy and safety and tolerability of the Rotigotine patch in subjects with early-stage idiopathic Parkinson's Disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 217 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 SP512 Trial to Assess the Safety of Long-Term Treatment of Rotigotine in Subjects With Early-Stage Idiopathic Parkinson's Disease.
• Study Start Date: Jun 1, 2002
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rotigotine Rotigotine	Drug: Rotigotine; Rotigotine trans-dermal patches: 10 cm2 (2 mg/24 hours); 20 cm2 (4 mg/24 hours); 30 cm2 (6 mg/24 hours); 40 cm2 (8 mg/24 hours) Optimal dosing: During the first year: The maximum Rotigotine dose allowed is 6 mg/24 hours. After the first year: allowed dose increase of Rotigotine up to a maximum of 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 [7 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. [7 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 9 (end of year 1), Visit 13 (end of year 2), Visit 17 (end of year 3), Visit 21(end of year 4), Visit 25 (end of year 5), Visit 29 (end of year 6), End of Treatment (last study visit or early withdrawal visit)]

   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 six months of maintenance treatment in the SP512 double-blind trial

Exclusion Criteria:

• Subjects who had an ongoing serious adverse event from SP512 double-blind trial that was assessed as related to study medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Peoria	Arizona	United States
2		Phoenix	Arizona	United States
3		Tucson	Arizona	United States
4		Fountain Valley	California	United States
5		Fresno	California	United States
6		Los Angeles	California	United States
7		Englewood	Colorado	United States
8		Danbury	Connecticut	United States
9		New Haven	Connecticut	United States
10		Miami	Florida	United States
11		Pompano Beach	Florida	United States
12		Sunrise	Florida	United States
13		Atlanta	Georgia	United States
14		Chicago	Illinois	United States
15		Fort Wayne	Indiana	United States
16		New Orleans	Louisiana	United States
17		Boston	Massachusetts	United States
18		Southfield	Michigan	United States
19		Minneapolis	Minnesota	United States
20		St. Louis	Missouri	United States
21		Henderson	Nevada	United States
22		New Brunswick	New Jersey	United States
23		Albany	New York	United States
24		Louisville	New York	United States
25		New York	New York	United States
26		Asheville	North Carolina	United States
27		Durham	North Carolina	United States
28		Cleveland	Ohio	United States
29		Columbus	Ohio	United States
30		Toledo	Ohio	United States
31		Upland	Pennsylvania	United States
32		Dallas	Texas	United States
33		Houston	Texas	United States
34		San Antonio	Texas	United States
35		Richmond	Virginia	United States
36		Roanoke	Virginia	United States
37		Milwaukee	Wisconsin	United States
38		Calgary	Alberta	Canada
39		Edmonton	Alberta	Canada
40		Vernon	British Columbia	Canada
41		Ottawa	Ontario	Canada
42		Saskatoon	Saskatchewan	Canada

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: NCT00594165
• Other Study ID Numbers: SP0702; SP512OL
• First Posted: Jan 15, 2008
• Last Update Posted: Oct 2, 2014
• Last Verified: Sep 1, 2010

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

Study Results

Participant Flow

Recruitment Details	An Open-Label Extension to Assess the Safety of Long-Term Treatment of Rotigotine in Subjects with Early-Stage Idiopathic Parkinson's Disease from June 2002 to November 2008
Pre-assignment Detail	Subject 10806 received SP512OL study medication at the final visit of SP512DB but never returned to the clinic; this subject is excluded from the Safety Set.

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Year 1, the maximum dose allowed is 6 mg/24 hours. After Year 1, a dose increase is allowed up to a maximum of 16 mg/24 hours.
Period Title: Overall Study
STARTED	217
COMPLETED	0
NOT COMPLETED	217

Baseline Characteristics

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Year 1, the maximum dose allowed is 6 mg/24 hours. After Year 1, a dose increase is allowed up to a maximum of 16 mg/24 hours.
Overall Participants	216
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	119 55.1%
>=65 years	97 44.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.2 (10.3)
Sex: Female, Male (Count of Participants)
Female	69 31.9%
Male	147 68.1%
Region of Enrollment (participants) [Number]
United States	186 86.1%
Canada	30 13.9%

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	7 years

Outcome Measure Data

Analysis Population Description

Of the 217 subjects who entered the study, 216 are included in this summary based on the Safety Set (SS). Subject 10806 received SP512OL study medication at the final visit of SP512DB but never returned to the clinic; this subject is excluded from the Safety Set.

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Year 1, the maximum dose allowed is 6 mg/24 hours. After Year 1, a dose increase is allowed up to a maximum of 16 mg/24 hours.
Measure Participants	216
Number [Subjects]	214

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	7 years

Outcome Measure Data

Analysis Population Description

Of the 217 subjects who entered the study, 216 are included in this summary based on the Safety Set (SS). Subject 10806 received SP512OL study medication at the final visit of SP512DB but never returned to the clinic; this subject is excluded from the Safety Set.

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Year 1, the maximum dose allowed is 6 mg/24 hours. After Year 1, a dose increase is allowed up to a maximum of 16 mg/24 hours.
Measure Participants	216
Number [subjects]	52

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 9 (end of year 1), Visit 13 (end of year 2), Visit 17 (end of year 3), Visit 21(end of year 4), Visit 25 (end of year 5), Visit 29 (end of year 6), End of Treatment (last study visit or early withdrawal visit)

Outcome Measure Data

Analysis Population Description

Of the 217 subjects who entered the study, 216 are included in this summary based on the Safety Set (SS). Subject 10806 received SP512OL study medication at the final visit of SP512DB but never returned to the clinic; this subject is excluded from the Safety Set. Last observation carried forward (LOCF) was utilized.

Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Year 1, the maximum dose allowed is 6 mg/24 hours. After Year 1, a dose increase is allowed up to a maximum of 16 mg/24 hours.
Measure Participants	216
Visit 9 (end of year 1) (n=209)	7.3 (4.4)
Visit 13 (end of year 2) (n=209)	7.9 (4.9)
Visit 17 (end of year 3) (n=209)	8.2 (5.2)
Visit 21 (end of year 4) (n=209)	8.4 (5.0)
Visit 25 (end of year 5) (n=209)	8.8 (5.0)
Visit 29 (end of year 6) (n=209)	8.5 (5.0)
End of Treatment (n=216)	9.0 (5.4)

Adverse Events

Time Frame	Up to 7 years
Adverse Event Reporting Description	Subject 10806 received SP512OL study medication at the final visit of SP512DB but never returned to the clinic; this subject is excluded from the Safety Set. Adverse event terms may appear in both summaries given that the same adverse event term may be reported for different subjects as either serious or non-serious.
Arm/Group Title	Rotigotine
Arm/Group Description	Optimal dosing for Rotigotine transdermal patches, once daily: Year 1, the maximum dose allowed is 6 mg/24 hours. After Year 1, a dose increase is allowed up to a maximum of 16 mg/24 hours.
All Cause Mortality
	Rotigotine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rotigotine
	Affected / at Risk (%)	# Events
Total	102/216 (47.2%)
Blood and lymphatic system disorders
Anaemia	1/216 (0.5%)	2
Cardiac disorders
Myocardial infarction	6/216 (2.8%)	6
Angina pectoris	1/216 (0.5%)	1
Angina unstable	1/216 (0.5%)	1
Coronary artery disease	3/216 (1.4%)	3
Coronary artery occlusion	2/216 (0.9%)	2
Arteriosclerosis coronary artery	1/216 (0.5%)	1
Arrhythmia	3/216 (1.4%)	3
Cardiac failure congestive	2/216 (0.9%)	2
Atrioventricular block third degree	1/216 (0.5%)	1
Atrioventricular block second degree	1/216 (0.5%)	1
Atrial fibrillation	1/216 (0.5%)	1
Sick sinus syndrome	1/216 (0.5%)	1
Ventricular tachycardia	1/216 (0.5%)	2
Gastrointestinal disorders
Lower gastrointestinal haemmorrhage	2/216 (0.9%)	2
Gastrointestinal haemorrhage	2/216 (0.9%)	4
Abdominal pain	2/216 (0.9%)	2
Abdominal pain upper	1/216 (0.5%)	1
Inguinal hernia	2/216 (0.9%)	2
Abdominal strangulated hernia	1/216 (0.5%)	1
Diarrhoea	1/216 (0.5%)	1
Constipation	1/216 (0.5%)	1
Faecal incontinence	1/216 (0.5%)	1
Umbilical hernia	1/216 (0.5%)	1
Small intestinal obstruction	1/216 (0.5%)	1
Erosive oesophagitis	1/216 (0.5%)	1
Pancreatitis	1/216 (0.5%)	1
General disorders
Chest pain	6/216 (2.8%)	7
Asthenia	2/216 (0.9%)	2
Oedema peripheral	2/216 (0.9%)	2
Pyrexia	1/216 (0.5%)	1
Application site reaction	1/216 (0.5%)	1
Hepatobiliary disorders
Cholangitis	1/216 (0.5%)	1
Cholecystitis	1/216 (0.5%)	1
Infections and infestations
Pneumonia	5/216 (2.3%)	8
Diverticulitis	1/216 (0.5%)	1
Gastroenteritis	1/216 (0.5%)	1
Appendicitis	1/216 (0.5%)	1
Urinary tract infection	3/216 (1.4%)	3
Infection	2/216 (0.9%)	3
Localised infection	1/216 (0.5%)	1
Wound infection	1/216 (0.5%)	1
Osteomyelitis	1/216 (0.5%)	1
Endocarditis	1/216 (0.5%)	1
Staphylococcal bacteraemia	1/216 (0.5%)	1
Staphylococcal infection	1/216 (0.5%)	1
Cellulitis	1/216 (0.5%)	1
Sepsis	1/216 (0.5%)	1
Injury, poisoning and procedural complications
Hip fracture	5/216 (2.3%)	6
Femoral neck fracture	1/216 (0.5%)	1
Foot fracture	1/216 (0.5%)	1
Fall	3/216 (1.4%)	3
Road traffic accident	1/216 (0.5%)	1
Tendon rupture	3/216 (1.4%)	3
Incision site haematoma	1/216 (0.5%)	1
Procedural pain	1/216 (0.5%)	1
Back injury	1/216 (0.5%)	1
Limb injury	1/216 (0.5%)	1
Lumbar vertebral fracture	1/216 (0.5%)	1
Strernal fracture	1/216 (0.5%)	1
Device dislocation	1/216 (0.5%)	1
Investigations
Electrocardiogram ST-T change	1/216 (0.5%)	1
Hepatic enzyme increased	1/216 (0.5%)	1
Metabolism and nutrition disorders
Dehydration	2/216 (0.9%)	2
Hypercalcaemia	1/216 (0.5%)	1
Hypoglycaemia	1/216 (0.5%)	1
Musculoskeletal and connective tissue disorders
Spinal column stenosis	4/216 (1.9%)	4
Lumbar spinal stenosis	3/216 (1.4%)	3
Scoliosis	1/216 (0.5%)	1
Musculoskeletal chest pain	3/216 (1.4%)	3
Pain in extremity	2/216 (0.9%)	2
Back pain	2/216 (0.9%)	2
Musculoskeletal pain	1/216 (0.5%)	1
Osteoarthritis	5/216 (2.3%)	7
Spinal osteoarthritis	1/216 (0.5%)	1
Arthralgia	3/216 (1.4%)	3
Muscular weakness	2/216 (0.9%)	2
Groin pain	1/216 (0.5%)	1
Arthritis	1/216 (0.5%)	3
Osteonecrosis	1/216 (0.5%)	1
Acquired claw toe	1/216 (0.5%)	1
Intervertebral disc protrusion	1/216 (0.5%)	1
Rotator cuff syndrome	1/216 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	3/216 (1.4%)	3
Bile duct cancer	1/216 (0.5%)	1
Ovarian epithelial cancer	1/216 (0.5%)	1
Uterine leiomyoma	1/216 (0.5%)	1
Endometrial cancer	1/216 (0.5%)	1
Renal cell carcinoma stage unspecified	1/216 (0.5%)	1
Salivary gland neoplasm	1/216 (0.5%)	1
Nervous system disorders
Parkinson's disease	5/216 (2.3%)	7
Parkinsonism	1/216 (0.5%)	1
Syncope	4/216 (1.9%)	5
Depressed level of consciousness	1/216 (0.5%)	1
Somnolence	1/216 (0.5%)	1
Tremor	2/216 (0.9%)	2
Carotid artery occulusion	1/216 (0.5%)	1
Cerebrovascular accident	1/216 (0.5%)	1
Dyskinesia	1/216 (0.5%)	1
Hypoaesthesia	1/216 (0.5%)	1
Presyncope	1/216 (0.5%)	1
Nerve root compression	1/216 (0.5%)	1
Psychiatric disorders
Hallucination	3/216 (1.4%)	3
Hallucination, visual	1/216 (0.5%)	1
Sleep attacks	2/216 (0.9%)	3
Suicidal ideation	1/216 (0.5%)	1
Suicide attempt	1/216 (0.5%)	1
Abnormal behaviour	1/216 (0.5%)	1
Confusional state	1/216 (0.5%)	1
Renal and urinary disorders
Urinary retention	2/216 (0.9%)	2
Nephrolithiasis	1/216 (0.5%)	1
Reproductive system and breast disorders
Ovarian cyst	1/216 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory distress	2/216 (0.9%)	2
Respiratory failure	1/216 (0.5%)	1
Accute respiratory failure	1/216 (0.5%)	1
Pulmonary embolism	4/216 (1.9%)	4
Obstructuve airways disorder	1/216 (0.5%)	1
Chronic obstructive pulmonary disease	1/216 (0.5%)	1
Pneumonia aspiration	1/216 (0.5%)	1
Epistaxis	1/216 (0.5%)	1
Surgical and medical procedures
Spinal laminectomy	2/216 (0.9%)	2
Intervertebral disc operation	1/216 (0.5%)	1
Cholecystectomy	1/216 (0.5%)	1
Hip arthroplasty	1/216 (0.5%)	2
Vascular disorders
Orthostatic hypotension	2/216 (0.9%)	2
Hypotension	1/216 (0.5%)	1
Angiopathy	1/216 (0.5%)	1
Haemorrhage	1/216 (0.5%)	1
Bleeding varicose vein	1/216 (0.5%)	1
Aortic aneurysm rupture	1/216 (0.5%)	1
Deep vein thrombosis	1/216 (0.5%)	1
Hypertension	1/216 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Rotigotine
	Affected / at Risk (%)	# Events
Total	206/216 (95.4%)
Blood and lymphatic system disorders
Anaemia	17/216 (7.9%)	19
Eye disorders
Cataract	25/216 (11.6%)	39
Gastrointestinal disorders
Nausea	66/216 (30.6%)	110
Vomiting	26/216 (12%)	44
Constipation	37/216 (17.1%)	42
Dyspepsia	19/216 (8.8%)	19
Diarrhoea	17/216 (7.9%)	21
Dry mouth	15/216 (6.9%)	16
General disorders
Oedema peripheral	79/216 (36.6%)	121
Application site erythema	31/216 (14.4%)	34
Application site pruritus	19/216 (8.8%)	25
Application site irritation	14/216 (6.5%)	14
Fatigue	24/216 (11.1%)	27
Infections and infestations
Upper respiratory tract infection	33/216 (15.3%)	49
Nasopharyngitis	25/216 (11.6%)	30
Sinusitis	17/216 (7.9%)	21
Urinary tract infection	33/216 (15.3%)	56
Influenza	17/216 (7.9%)	18
Injury, poisoning and procedural complications
Fall	69/216 (31.9%)	142
Excoriation	12/216 (5.6%)	14
Contusion	15/216 (6.9%)	18
Skin laceration	15/216 (6.9%)	20
Procedural pain	14/216 (6.5%)	16
Investigations
Weight decreased	14/216 (6.5%)	16
Blood cholesterol increased	11/216 (5.1%)	11
Musculoskeletal and connective tissue disorders
Back pain	53/216 (24.5%)	69
Pain in extremity	40/216 (18.5%)	63
Neck pain	12/216 (5.6%)	12
Arthralgia	51/216 (23.6%)	82
Joint swelling	15/216 (6.9%)	16
Muscle spasms	21/216 (9.7%)	25
Osteoarthritis	12/216 (5.6%)	16
Muscular weakness	10/216 (4.6%)	12
Musculoskeletal pain	14/216 (6.5%)	17
Nervous system disorders
Somnolence	116/216 (53.7%)	198
Dizziness	58/216 (26.9%)	80
Paraesthesia	16/216 (7.4%)	23
Hypoaesthesia	14/216 (6.5%)	21
Headache	21/216 (9.7%)	32
Tremor	19/216 (8.8%)	22
Memory impairment	14/216 (6.5%)	14
Balance disorder	14/216 (6.5%)	16
Dyskinesia	12/216 (5.6%)	13
Parkinson's disease	12/216 (5.6%)	12
Psychiatric disorders
Insomnia	47/216 (21.8%)	55
Depression	38/216 (17.6%)	45
Anxiety	24/216 (11.1%)	28
Hallucination	20/216 (9.3%)	28
Confusional state	17/216 (7.9%)	19
Sleep disorder	14/216 (6.5%)	16
Abnormal dreams	13/216 (6%)	16
Obsessive-compulsive disorder	12/216 (5.6%)	14
Renal and urinary disorders
Micturition urgency	14/216 (6.5%)	14
Urinary incontinence	12/216 (5.6%)	14
Reproductive system and breast disorders
Erectile dysfunction	19/216 (8.8%)	20
Respiratory, thoracic and mediastinal disorders
Cough	17/216 (7.9%)	29
Dyspnoea	13/216 (6%)	13
Pharyngolaryngeal pain	12/216 (5.6%)	15
Skin and subcutaneous tissue disorders
Rash	15/216 (6.9%)	17
Vascular disorders
Hypertension	27/216 (12.5%)	27
Orthostatic hypotension	12/216 (5.6%)	14

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.