Trial Outcomes & Findings for An Open-Label Extension Trial to Assess the Safety of Long-Term Treatment of Rotigotine in Early-Stage Parkinson's Disease. (NCT NCT00594165)

Last Updated: 2014-10-02

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

217 participants

Primary outcome timeframe

7 years

Results posted on

2014-10-02

Participant Flow

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

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.

Participant milestones

Participant milestones
Measure	Rotigotine 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 Study STARTED	217
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	217

Reasons for withdrawal

Reasons for withdrawal
Measure	Rotigotine 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 Study Major protocol violation	1
Overall Study Lack of Efficacy	12
Overall Study Adverse Event	52
Overall Study Unsatisfactory compliance of subject	6
Overall Study Subject withdrew consent	27
Overall Study Study ended per sponsor	102
Overall Study Lost to Follow-up	4
Overall Study Other: PI discretion	5
Overall Study Other: Subject moving	3
Overall Study Other: Brain surgery controlled symptoms	1
Overall Study Other: House bound; can't get to clinic	1
Overall Study Other: Subject enrolled in other trial	1
Overall Study Other: Site terminated participation	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rotigotine n=216 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	119 Participants n=5 Participants
Age, Categorical >=65 years	97 Participants n=5 Participants
Age, Continuous	63.2 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants
Sex: Female, Male Male	147 Participants n=5 Participants
Region of Enrollment United States	186 participants n=5 Participants
Region of Enrollment Canada	30 participants n=5 Participants

PRIMARY outcome

Timeframe: 7 years

Population: 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.

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

Outcome measures

Outcome measures
Measure	Rotigotine n=216 Participants 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.
Number of Subjects With at Least One Adverse Event During This Open-label Extension Study	214 Subjects

SECONDARY outcome

Timeframe: 7 years

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

Outcome measures

Outcome measures
Measure	Rotigotine n=216 Participants 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.
Number of Subjects Who Withdrew From the Trial Due to an Adverse Event.	52 subjects

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rotigotine n=216 Participants 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.
Mean Epworth Sleepiness Scale Score During the Open-label Extension. Visit 9 (end of year 1) (n=209)	7.3 Score on a scale Standard Deviation 4.4
Mean Epworth Sleepiness Scale Score During the Open-label Extension. Visit 13 (end of year 2) (n=209)	7.9 Score on a scale Standard Deviation 4.9
Mean Epworth Sleepiness Scale Score During the Open-label Extension. Visit 17 (end of year 3) (n=209)	8.2 Score on a scale Standard Deviation 5.2
Mean Epworth Sleepiness Scale Score During the Open-label Extension. Visit 21 (end of year 4) (n=209)	8.4 Score on a scale Standard Deviation 5.0
Mean Epworth Sleepiness Scale Score During the Open-label Extension. Visit 25 (end of year 5) (n=209)	8.8 Score on a scale Standard Deviation 5.0
Mean Epworth Sleepiness Scale Score During the Open-label Extension. Visit 29 (end of year 6) (n=209)	8.5 Score on a scale Standard Deviation 5.0
Mean Epworth Sleepiness Scale Score During the Open-label Extension. End of Treatment (n=216)	9.0 Score on a scale Standard Deviation 5.4

Adverse Events

Rotigotine

Serious events: 102 serious events

Other events: 206 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rotigotine n=216 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.46% 1/216 • Number of events 2 • Up to 7 years 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.
Cardiac disorders Myocardial infarction	2.8% 6/216 • Number of events 6 • Up to 7 years 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.
Cardiac disorders Angina pectoris	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Cardiac disorders Angina unstable	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Cardiac disorders Coronary artery disease	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Cardiac disorders Coronary artery occlusion	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Cardiac disorders Arteriosclerosis coronary artery	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Cardiac disorders Arrhythmia	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Cardiac disorders Cardiac failure congestive	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Cardiac disorders Atrioventricular block third degree	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Cardiac disorders Atrioventricular block second degree	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Cardiac disorders Atrial fibrillation	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Cardiac disorders Sick sinus syndrome	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Cardiac disorders Ventricular tachycardia	0.46% 1/216 • Number of events 2 • Up to 7 years 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.
Gastrointestinal disorders Lower gastrointestinal haemmorrhage	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.93% 2/216 • Number of events 4 • Up to 7 years 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.
Gastrointestinal disorders Abdominal pain	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Gastrointestinal disorders Abdominal pain upper	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Gastrointestinal disorders Inguinal hernia	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Gastrointestinal disorders Abdominal strangulated hernia	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Gastrointestinal disorders Diarrhoea	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Gastrointestinal disorders Constipation	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Gastrointestinal disorders Faecal incontinence	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Gastrointestinal disorders Umbilical hernia	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Gastrointestinal disorders Small intestinal obstruction	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Gastrointestinal disorders Erosive oesophagitis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Gastrointestinal disorders Pancreatitis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
General disorders Chest pain	2.8% 6/216 • Number of events 7 • Up to 7 years 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.
General disorders Asthenia	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
General disorders Oedema peripheral	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
General disorders Pyrexia	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
General disorders Application site reaction	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Hepatobiliary disorders Cholangitis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Hepatobiliary disorders Cholecystitis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Pneumonia	2.3% 5/216 • Number of events 8 • Up to 7 years 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.
Infections and infestations Diverticulitis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Gastroenteritis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Appendicitis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Urinary tract infection	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Infections and infestations Infection	0.93% 2/216 • Number of events 3 • Up to 7 years 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.
Infections and infestations Localised infection	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Wound infection	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Osteomyelitis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Endocarditis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Staphylococcal bacteraemia	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Staphylococcal infection	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Cellulitis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Infections and infestations Sepsis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Hip fracture	2.3% 5/216 • Number of events 6 • Up to 7 years 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.
Injury, poisoning and procedural complications Femoral neck fracture	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Foot fracture	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Fall	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Injury, poisoning and procedural complications Road traffic accident	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Tendon rupture	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Injury, poisoning and procedural complications Incision site haematoma	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Procedural pain	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Back injury	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Limb injury	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Strernal fracture	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Injury, poisoning and procedural complications Device dislocation	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Investigations Electrocardiogram ST-T change	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Investigations Hepatic enzyme increased	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Metabolism and nutrition disorders Dehydration	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Metabolism and nutrition disorders Hypercalcaemia	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Metabolism and nutrition disorders Hypoglycaemia	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Spinal column stenosis	1.9% 4/216 • Number of events 4 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Scoliosis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Pain in extremity	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Back pain	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Osteoarthritis	2.3% 5/216 • Number of events 7 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Arthralgia	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Muscular weakness	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Groin pain	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Arthritis	0.46% 1/216 • Number of events 3 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Acquired claw toe	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct cancer	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian epithelial cancer	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma stage unspecified	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland neoplasm	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Nervous system disorders Parkinson's disease	2.3% 5/216 • Number of events 7 • Up to 7 years 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.
Nervous system disorders Parkinsonism	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Nervous system disorders Syncope	1.9% 4/216 • Number of events 5 • Up to 7 years 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.
Nervous system disorders Depressed level of consciousness	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Nervous system disorders Somnolence	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Nervous system disorders Tremor	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Nervous system disorders Carotid artery occulusion	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Nervous system disorders Cerebrovascular accident	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Nervous system disorders Dyskinesia	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Nervous system disorders Hypoaesthesia	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Nervous system disorders Presyncope	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Nervous system disorders Nerve root compression	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Psychiatric disorders Hallucination	1.4% 3/216 • Number of events 3 • Up to 7 years 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.
Psychiatric disorders Hallucination, visual	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Psychiatric disorders Sleep attacks	0.93% 2/216 • Number of events 3 • Up to 7 years 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.
Psychiatric disorders Suicidal ideation	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Psychiatric disorders Suicide attempt	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Psychiatric disorders Abnormal behaviour	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Psychiatric disorders Confusional state	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Renal and urinary disorders Urinary retention	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Renal and urinary disorders Nephrolithiasis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Reproductive system and breast disorders Ovarian cyst	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Accute respiratory failure	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.9% 4/216 • Number of events 4 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Obstructuve airways disorder	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Surgical and medical procedures Spinal laminectomy	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Surgical and medical procedures Intervertebral disc operation	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Surgical and medical procedures Cholecystectomy	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Surgical and medical procedures Hip arthroplasty	0.46% 1/216 • Number of events 2 • Up to 7 years 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.
Vascular disorders Orthostatic hypotension	0.93% 2/216 • Number of events 2 • Up to 7 years 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.
Vascular disorders Hypotension	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Vascular disorders Angiopathy	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Vascular disorders Haemorrhage	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Vascular disorders Bleeding varicose vein	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Vascular disorders Aortic aneurysm rupture	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Vascular disorders Deep vein thrombosis	0.46% 1/216 • Number of events 1 • Up to 7 years 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.
Vascular disorders Hypertension	0.46% 1/216 • Number of events 1 • Up to 7 years 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.

Other adverse events

Other adverse events
Measure	Rotigotine n=216 participants at risk 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.
Blood and lymphatic system disorders Anaemia	7.9% 17/216 • Number of events 19 • Up to 7 years 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.
Eye disorders Cataract	11.6% 25/216 • Number of events 39 • Up to 7 years 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.
Gastrointestinal disorders Nausea	30.6% 66/216 • Number of events 110 • Up to 7 years 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.
Gastrointestinal disorders Vomiting	12.0% 26/216 • Number of events 44 • Up to 7 years 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.
Gastrointestinal disorders Constipation	17.1% 37/216 • Number of events 42 • Up to 7 years 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.
Gastrointestinal disorders Dyspepsia	8.8% 19/216 • Number of events 19 • Up to 7 years 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.
Gastrointestinal disorders Diarrhoea	7.9% 17/216 • Number of events 21 • Up to 7 years 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.
Gastrointestinal disorders Dry mouth	6.9% 15/216 • Number of events 16 • Up to 7 years 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.
General disorders Oedema peripheral	36.6% 79/216 • Number of events 121 • Up to 7 years 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.
General disorders Application site erythema	14.4% 31/216 • Number of events 34 • Up to 7 years 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.
General disorders Application site pruritus	8.8% 19/216 • Number of events 25 • Up to 7 years 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.
General disorders Application site irritation	6.5% 14/216 • Number of events 14 • Up to 7 years 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.
General disorders Fatigue	11.1% 24/216 • Number of events 27 • Up to 7 years 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.
Infections and infestations Upper respiratory tract infection	15.3% 33/216 • Number of events 49 • Up to 7 years 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.
Infections and infestations Nasopharyngitis	11.6% 25/216 • Number of events 30 • Up to 7 years 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.
Infections and infestations Sinusitis	7.9% 17/216 • Number of events 21 • Up to 7 years 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.
Infections and infestations Urinary tract infection	15.3% 33/216 • Number of events 56 • Up to 7 years 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.
Infections and infestations Influenza	7.9% 17/216 • Number of events 18 • Up to 7 years 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.
Injury, poisoning and procedural complications Fall	31.9% 69/216 • Number of events 142 • Up to 7 years 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.
Injury, poisoning and procedural complications Excoriation	5.6% 12/216 • Number of events 14 • Up to 7 years 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.
Injury, poisoning and procedural complications Contusion	6.9% 15/216 • Number of events 18 • Up to 7 years 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.
Injury, poisoning and procedural complications Skin laceration	6.9% 15/216 • Number of events 20 • Up to 7 years 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.
Injury, poisoning and procedural complications Procedural pain	6.5% 14/216 • Number of events 16 • Up to 7 years 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.
Investigations Weight decreased	6.5% 14/216 • Number of events 16 • Up to 7 years 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.
Investigations Blood cholesterol increased	5.1% 11/216 • Number of events 11 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Back pain	24.5% 53/216 • Number of events 69 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Pain in extremity	18.5% 40/216 • Number of events 63 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Neck pain	5.6% 12/216 • Number of events 12 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Arthralgia	23.6% 51/216 • Number of events 82 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Joint swelling	6.9% 15/216 • Number of events 16 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Muscle spasms	9.7% 21/216 • Number of events 25 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Osteoarthritis	5.6% 12/216 • Number of events 16 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Muscular weakness	4.6% 10/216 • Number of events 12 • Up to 7 years 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.
Nervous system disorders Somnolence	53.7% 116/216 • Number of events 198 • Up to 7 years 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.
Nervous system disorders Dizziness	26.9% 58/216 • Number of events 80 • Up to 7 years 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.
Nervous system disorders Paraesthesia	7.4% 16/216 • Number of events 23 • Up to 7 years 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.
Nervous system disorders Hypoaesthesia	6.5% 14/216 • Number of events 21 • Up to 7 years 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.
Nervous system disorders Headache	9.7% 21/216 • Number of events 32 • Up to 7 years 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.
Nervous system disorders Tremor	8.8% 19/216 • Number of events 22 • Up to 7 years 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.
Nervous system disorders Memory impairment	6.5% 14/216 • Number of events 14 • Up to 7 years 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.5% 14/216 • Number of events 17 • Up to 7 years 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.
Nervous system disorders Balance disorder	6.5% 14/216 • Number of events 16 • Up to 7 years 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.
Nervous system disorders Dyskinesia	5.6% 12/216 • Number of events 13 • Up to 7 years 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.
Nervous system disorders Parkinson's disease	5.6% 12/216 • Number of events 12 • Up to 7 years 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.
Psychiatric disorders Insomnia	21.8% 47/216 • Number of events 55 • Up to 7 years 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.
Psychiatric disorders Depression	17.6% 38/216 • Number of events 45 • Up to 7 years 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.
Psychiatric disorders Anxiety	11.1% 24/216 • Number of events 28 • Up to 7 years 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.
Psychiatric disorders Hallucination	9.3% 20/216 • Number of events 28 • Up to 7 years 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.
Psychiatric disorders Confusional state	7.9% 17/216 • Number of events 19 • Up to 7 years 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.
Psychiatric disorders Sleep disorder	6.5% 14/216 • Number of events 16 • Up to 7 years 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.
Psychiatric disorders Abnormal dreams	6.0% 13/216 • Number of events 16 • Up to 7 years 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.
Psychiatric disorders Obsessive-compulsive disorder	5.6% 12/216 • Number of events 14 • Up to 7 years 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.
Renal and urinary disorders Micturition urgency	6.5% 14/216 • Number of events 14 • Up to 7 years 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.
Renal and urinary disorders Urinary incontinence	5.6% 12/216 • Number of events 14 • Up to 7 years 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.
Reproductive system and breast disorders Erectile dysfunction	8.8% 19/216 • Number of events 20 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Cough	7.9% 17/216 • Number of events 29 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.0% 13/216 • Number of events 13 • Up to 7 years 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.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	5.6% 12/216 • Number of events 15 • Up to 7 years 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.
Skin and subcutaneous tissue disorders Rash	6.9% 15/216 • Number of events 17 • Up to 7 years 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.
Vascular disorders Hypertension	12.5% 27/216 • Number of events 27 • Up to 7 years 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.
Vascular disorders Orthostatic hypotension	5.6% 12/216 • Number of events 14 • Up to 7 years 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.

Additional Information

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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 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.
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