Long-term Open-label Trial in Idiopathic Restless Legs Syndrome (RLS)

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00498186
• Collaborator: (none)
• Enrollment: 295
• Locations: 24
• Arm: 1
• Duration (Months): 69
• Patients Per Site: 12.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a multi-center, open-label extension trial conducted at the same European sites that participated in trial SP 709 (NCT00243217). The trial is designed to collect long-term safety and tolerability, efficacy correlates, and quality of life data in subjects with idiopathic Restless Leg Syndrome (RLS). The duration of treatment is approximately 5 years. Subject will be up-titrated to their optimal dose (administration of 1 patch per day, 5 different doses and patch sizes).

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome	Drug: Rotigotine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 295 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Extension Trial to Determine Safety and Tolerability of Long-term Transdermal Application of Rotigotine in Subjects With Idiopathic Restless Legs Syndrome
• Study Start Date: Jul 1, 2003
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rotigotine Rotigotine trans-dermal patch	Drug: Rotigotine; Rotigotine transdermal patches once daily: 2.5cm2 (0.5mg/24 hours) 5cm2 (1mg/24 hours) 10cm2 (2mg/24 hours) 15cm2 (3mg/24 hours) 20cm2 (4mg/24 hours); Other Names: Neupro®

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With at Least One Adverse Event, as Reported Spontaneously by the Subject or Observed by the Investigator, During the 5-year Open-label Extension. [Up to 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 During the 5-year Open Label Extension [Up to five years]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject has completed the preceding trial SP709 (NCT00243217)

Exclusion Criteria:

• Subject did suffer from a serious adverse event during trial SP709 (NCT00243217) which is ongoing at the end of that trial and is assessed to be related to the study medication by the investigator and/or the Sponsor

• Sleep disturbances

• Further clinically relevant concomitant diseases such as polyneuropathy, akathisia, claudication, varicosis, muscle fasciculation, painful legs and moving toes, or radiculopathy

• Other central nervous diseases

• One psychotic episode since start of study SP709

• Any medical or psychiatric condition, which in the opinion of the investigator can jeopardize or would compromise the subject's ability to participate in this trial

• Clinically relevant cardiac dysfunction and arrhythmias

• The subject has at entry in study SP710, a QTc interval ≥ 500 msec and/or a QTc interval which has increased by ≥ 60 msec as compared to the average baseline (Visit

1. QTc interval of study SP709

• Subject has clinically relevant renal dysfunction (serum creatine ≥ 2.0 mg/dl)

• Subject has clinically relevant hepatic dysfunction (total bilirubin > 2.0 mg/dl or ALT and/or AST greater than two times the upper limit of the reference range

• Subject has a newly diagnosed or relapsing neoplastic disease since the start of study SP709

• Subject has a known hypersensitivity to any components of the trial medication or comparative drugs as stated in this protocol

• Subject needs drugs prohibited in the course of this trial: neuroleptics, bupidine, hypnotics, antidepressants, anxiolytic drugs, anticonvulsive therapy, psychostimulatory drugs, other L-Dopa or dopamine agonist therapy, opioids, benzodiazepines, MAO inhibitors, sedative antihistamines, amphetamines

• Subject is abusing alcohol or drug since start of SP709

• Subject is pregnant or nursing or woman of child-bearing potential who is not surgically sterile, two years postmenopausal, or does not practice two combined methods of contraception, unless sexually abstinent

• Subject pursues shift work or is subject to other continuous non-disease-related life conditions which do not allow regular sleep at night

• Subject has clinically relevant vasculopathies (eg, varix or arteriosclerosis)

• Subject has significant skin hypersensitivity to adhesive or other transdermals or recent unresolved contact dermatitis

• Subject has symptomatic orthostatic hypotension, or a systolic blood pressure (SBP) less tham 105mmHg and/or a drop in SBP of > 20mmHg or a drop of > 10mmHg in diastolic BP (DBP) on standing at baseline visit (Visit 1)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Innsbruck		Austria
2		Bamberg		Germany
3		Berlin		Germany
4		Bielefeld		Germany
5		Gelsenkirchen		Germany
6		Gera		Germany
7		Halle		Germany
8		Jena		Germany
9		Kassel		Germany
10		Köthen		Germany
11		Marburg		Germany	35039
12		Mittweida		Germany
13		München		Germany
14		Neubrandenburg		Germany
15		Oldenburg		Germany
16		Regensburg		Germany
17		Schwalmstadt-Treysa		Germany
18		Schwerin		Germany
19		Tuttlingen		Germany
20		Ulm		Germany
21		Unterhaching		Germany
22		Alcira	Valencia	Spain
23		Barcelona		Spain
24		Madrid		Spain

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: NCT00498186
• Other Study ID Numbers: SP0710
• First Posted: Jul 9, 2007
• Last Update Posted: Oct 2, 2014
• Last Verified: Oct 1, 2011

• Keywords provided by UCB Pharma: Rotigotine; Neupro®
• Additional relevant MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome; Rotigotine

Study Results

Participant Flow

Recruitment Details	A total of 295 subjects belong to the Enrolled Set (ES) and all of them received at least one dose of trial medication, so they all belong to the Safety Set (SS).
Pre-assignment Detail	Participant Flow information and Baseline Characteristics belong to the Safety Set (SS).

Arm/Group Title	Rotigotine
Arm/Group Description	Rotigotine trans-dermal patch
Period Title: Overall Study
STARTED	295
COMPLETED	122
NOT COMPLETED	173

Baseline Characteristics

Arm/Group Title	Rotigotine
Arm/Group Description	Rotigotine trans-dermal patch
Overall Participants	295
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	208 70.5%
>=65 years	87 29.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.3 (10.1)
Sex: Female, Male (Count of Participants)
Female	196 66.4%
Male	99 33.6%
Body Mass Index (BMI) (kg/ m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/ m^2]	26.37 (3.84)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	167.5 (8.3)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	74.21 (13.19)

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With at Least One Adverse Event, as Reported Spontaneously by the Subject or Observed by the Investigator, During the 5-year Open-label Extension.
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	Up to five years

Outcome Measure Data

Analysis Population Description

Of the 295 subjects who entered the study, 295 are included in this summary based on the Safety Set (SS).

Arm/Group Title	Rotigotine
Arm/Group Description	Rotigotine trans-dermal patch
Measure Participants	295
Number [participants]	273 92.5%

2. Secondary Outcome

Title	Number of Subjects Who Withdrew From the Trial Due to an Adverse Event During the 5-year Open Label Extension
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	Up to five years

Outcome Measure Data

Analysis Population Description

Of the 295 subjects who entered the study, 295 are included in this summary based on the Safety Set (SS).

Arm/Group Title	Rotigotine
Arm/Group Description	Rotigotine trans-dermal patch
Measure Participants	295
Number [participants]	93 31.5%

Adverse Events

Time Frame	Adverse Events (AEs) were collected over the whole trial period up to 5 years 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 received at least one dose of trial medication.
Arm/Group Title	Rotigotine
Arm/Group Description	Rotigotine trans-dermal patch
All Cause Mortality
	Rotigotine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rotigotine
	Affected / at Risk (%)	# Events
Total	79/295 (26.8%)
Blood and lymphatic system disorders
Lymphadenopathy	1/295 (0.3%)	1
Cardiac disorders
Coronary artery disease	2/295 (0.7%)	2
Cardiac failure	1/295 (0.3%)	1
Myocardial infarction	4/295 (1.4%)	5
Angina pectoris	1/295 (0.3%)	1
Pericardial haemorrhage	1/295 (0.3%)	1
Bradycardia	1/295 (0.3%)	1
Tachycardia	1/295 (0.3%)	1
Tricuspid valve incompetence	1/295 (0.3%)	1
Endocrine disorders
Goitre	2/295 (0.7%)	2
Eye disorders
Diplopia	1/295 (0.3%)	1
Gastrointestinal disorders
Gastric ulcer haemorrhage	1/295 (0.3%)	1
Abdominal pain	1/295 (0.3%)	1
Inguinal hernia	1/295 (0.3%)	1
Nausea	2/295 (0.7%)	2
Haematochezia	1/295 (0.3%)	1
General disorders
Fatigue	1/295 (0.3%)	1
Hernia	1/295 (0.3%)	1
Inflammation	1/295 (0.3%)	1
Cyst	1/295 (0.3%)	1
Necrosis	1/295 (0.3%)	1
Oedema peripheral	1/295 (0.3%)	1
Hepatobiliary disorders
Cholecystitis acute	1/295 (0.3%)	1
Infections and infestations
Appendicitis	1/295 (0.3%)	1
Gastroenteritis	1/295 (0.3%)	1
Perianal abscess	1/295 (0.3%)	1
Lower respiratory tract infection	1/295 (0.3%)	1
Pneumonia	1/295 (0.3%)	1
Pyelonephritis	1/295 (0.3%)	1
Pyelonephritis chronic	1/295 (0.3%)	1
Injury, poisoning and procedural complications
Concussion	1/295 (0.3%)	1
Comminuted fracture	1/295 (0.3%)	1
Joint dislocation	1/295 (0.3%)	1
Multiple fractures	1/295 (0.3%)	1
Meniscus lesion	1/295 (0.3%)	1
Ankle fracture	1/295 (0.3%)	1
Tendon rupture	1/295 (0.3%)	1
Incisional hernia	1/295 (0.3%)	1
Facial bones fracture	1/295 (0.3%)	1
Radius fracture	3/295 (1%)	3
Investigations
Blood pressure increased	1/295 (0.3%)	2
Musculoskeletal and connective tissue disorders
Chondropathy	1/295 (0.3%)	1
Toe deformity	4/295 (1.4%)	4
Intervertebral disc disorder	1/295 (0.3%)	1
Intervertebral disc protrusion	1/295 (0.3%)	1
Impingement syndrome	1/295 (0.3%)	1
Periarthritis	1/295 (0.3%)	1
Rotator cuff syndrome	1/295 (0.3%)	1
Arthralgia	1/295 (0.3%)	1
Muscle tightness	1/295 (0.3%)	1
Back pain	1/295 (0.3%)	1
Osteoarthritis	11/295 (3.7%)	13
Lumbal spinal stenosis	1/295 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Salivary gland adenoma	1/295 (0.3%)	1
Colon adenoma	1/295 (0.3%)	1
Plasmacytoma	1/295 (0.3%)	1
Prostate cancer	1/295 (0.3%)	1
Bladder neoplasm	1/295 (0.3%)	1
Uterine leiomyoma	3/295 (1%)	3
Nervous system disorders
Polyneuropathy	1/295 (0.3%)	1
Cerebellar infarction	1/295 (0.3%)	1
Cerebral ischaemia	1/295 (0.3%)	1
Cerebrovascular accident	1/295 (0.3%)	1
Syncope	3/295 (1%)	3
Depressed level of consciousness	1/295 (0.3%)	1
Tension headache	1/295 (0.3%)	1
Migraine	1/295 (0.3%)	1
Presyncope	1/295 (0.3%)	1
Restless legs syndrome	1/295 (0.3%)	1
Pregnancy, puerperium and perinatal conditions
Abortion	1/295 (0.3%)	1
Renal and urinary disorders
Bladder prolapse	1/295 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Sleep apnoe syndrome	2/295 (0.7%)	2
Pleurisy	1/295 (0.3%)	1
Surgical and medical procedures
Abdominoplasty	1/295 (0.3%)	1
Bladder operation	1/295 (0.3%)	1
Hip arthroplasty	2/295 (0.7%)	2
Limb operation	1/295 (0.3%)	1
Hysterectomy	1/295 (0.3%)	1
Angioplasty	1/295 (0.3%)	1
Vascular disorders
Arterial occlusive disease	1/295 (0.3%)	1
Arteriosclerosis	1/295 (0.3%)	1
Vascular occlusion	1/295 (0.3%)	1
Deep vein thrombosis	1/295 (0.3%)	1
Varicose vein	3/295 (1%)	3
Other (Not Including Serious) Adverse Events
	Rotigotine
	Affected / at Risk (%)	# Events
Total	272/295 (92.2%)
Gastrointestinal disorders
Nausea	35/295 (11.9%)	44
General disorders
Application site erythema	96/295 (32.5%)	132
Application site reaction	74/295 (25.1%)	90
Application site pruritus	54/295 (18.3%)	71
Fatigue	31/295 (10.5%)	36
Infections and infestations
Influenza	15/295 (5.1%)	17
Bronchitis	20/295 (6.8%)	26
Nasopharyngitis	55/295 (18.6%)	78
Musculoskeletal and connective tissue disorders
Arthralgia	21/295 (7.1%)	25
Back pain	40/295 (13.6%)	50
Osteoarthritis	19/295 (6.4%)	19
Nervous system disorders
Headache	16/295 (5.4%)	21
Dizziness	16/295 (5.4%)	20
Psychiatric disorders
Depression	22/295 (7.5%)	25
Insomnia	17/295 (5.8%)	18
Sleep disorder	21/295 (7.1%)	22
Skin and subcutaneous tissue disorders
Erythemas	17/295 (5.8%)	17
Pruritus	15/295 (5.1%)	16
Vascular disorders
Hypertension	26/295 (8.8%)	28

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.