Trial Outcomes & Findings for Effect on RLS Symptom Severity After Switching to Neupro® in Patients Who Previously Experienced Augmentation (NCT NCT01386944)

Last Updated: 2018-04-04

Results Overview

The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill subjects A negative change from Baseline to Visit 2 indicates an improvement in CGI Item 1.

Recruitment status

COMPLETED

Target enrollment

102 participants

Primary outcome timeframe

From Baseline up to 7 days

Results posted on

2018-04-04

Participant Flow

This non-interventional study (NIS) was conducted in 18 specialized centres (medical practice and outpatient department) for neurology throughout Germany. The Participant Flow refers to the Enrolled Set (ES). The ES consists of all patients who provided informed consent.

The physician was to decide freely to treat the patient with Neupro®. In this context, the physician was not to change routine practice in reaching treatment decisions and in treating his/her patients because of the study. The observational period was 13 months per patient (adjustment period of medication switch plus 12 months of observation).

Participant milestones

Participant milestones
Measure	Neupro® Treatment Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Overall Study STARTED	102
Overall Study COMPLETED	46
Overall Study NOT COMPLETED	56

Reasons for withdrawal

Reasons for withdrawal
Measure	Neupro® Treatment Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Overall Study Adverse Event	26
Overall Study Lack of Efficacy	14
Overall Study Lost to Follow-up	8
Overall Study Unspecified reason	8

Baseline Characteristics

Effect on RLS Symptom Severity After Switching to Neupro® in Patients Who Previously Experienced Augmentation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Neupro® Treatment n=97 Participants Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Age, Continuous	64.2 years STANDARD_DEVIATION 11.1 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	45 Participants n=5 Participants
Age, Categorical >=65 years	52 Participants n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants
Race/Ethnicity, Customized Scandinavian/Central European	90 participants n=5 Participants
Race/Ethnicity, Customized Southern European	5 participants n=5 Participants
Race/Ethnicity, Customized Missing	2 participants n=5 Participants
Height	168.43 centimeter STANDARD_DEVIATION 9.48 • n=5 Participants
Weight	81.69 kilogram STANDARD_DEVIATION 15.93 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline up to 7 days

Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and consists of all patients who received treatment with Neupro at least once and had a Visit 1 and at least one post-Visit 1 measurement on the primary variable documented.

Outcome measures

Outcome measures
Measure	Neupro® Treatment n=89 Participants Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 2	-0.8 score on a scale Standard Deviation 1.1 • Interval -1.0 to -0.5

PRIMARY outcome

Timeframe: From Baseline up to 28 days

Outcome measures

Outcome measures
Measure	Neupro® Treatment n=77 Participants Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 3	-1.4 score on a scale Standard Deviation 1.3 • Interval -1.5 to -1.0

PRIMARY outcome

Timeframe: From Baseline up to 4 months

Outcome measures

Outcome measures
Measure	Neupro® Treatment n=58 Participants Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 4	-1.8 score on a scale Standard Deviation 1.2 • Interval -2.0 to -1.5

PRIMARY outcome

Timeframe: From Baseline up to 7 months

Outcome measures

Outcome measures
Measure	Neupro® Treatment n=52 Participants Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 5	-2.0 score on a scale Standard Deviation 1.4 • Interval -2.5 to -1.5

PRIMARY outcome

Timeframe: From Baseline up to 10 months

Outcome measures

Outcome measures
Measure	Neupro® Treatment n=45 Participants Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 6	-2.0 score on a scale Standard Deviation 1.3 • Interval -2.5 to -1.5

PRIMARY outcome

Timeframe: From Baseline up to 13 months

Outcome measures

Outcome measures
Measure	Neupro® Treatment n=46 Participants Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 7	-1.8 score on a scale Standard Deviation 1.3 • Interval -2.0 to -1.5

SECONDARY outcome

Timeframe: From Baseline up to 28 days

Population: The Analysis Population refers to the Eligibility Completer Set (ECS). The ECS is a subset of the Completer Set excluding patients with Parkinson's disease and/or treated Polyneuropathy as concomitant disease identified by the preferred term (PT) of the MedDRA coding and patients treated with Neupro up to 4 weeks before Visit 1.

Case reports from clinical practice refer to different switching regimens for patients taking oral dopaminergics who experienced augmentation and then switched to Neupro®. The previous dopaminergic treatment might have been partly or completely down-titrated prior to switching to Neupro®. Physicians were requested to document the change of treatment at each recommended visit in the electronic Case Report Form (eCRF) considering their total clinical experience with this particular Restless Legs Syndrome (RLS) patients population. Documentation comprised changes in the RLS medication last prescribed, and the dosage of Neupro® and concomitant medications. The change of treatment regimen was entirely at the physicians' discretion.

Outcome measures

Outcome measures
Measure	Neupro® Treatment n=43 Participants Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study Switch after "Drug holiday"	5 participants
Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study Overnight Switch	23 participants
Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study Overlapping Switch	9 participants
Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study No Switch	6 participants

Adverse Events

Neupro® Treatment

Serious events: 9 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Neupro® Treatment n=99 participants at risk Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Gastrointestinal disorders Hiatus hernia	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Gastrointestinal disorders Diverticulum	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Gastrointestinal disorders Acquired oesophageal web	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
General disorders Irritability	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Infections and infestations Pneumonia	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Infections and infestations Urinary tract infection	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Metabolism and nutrition disorders Hypokalaemia	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	2.0% 2/99 • Number of events 2 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Psychiatric disorders Depression	2.0% 2/99 • Number of events 2 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Psychiatric disorders Personality change	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Psychiatric disorders Acute stress disorder	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Psychiatric disorders Thinking abnormal	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Renal and urinary disorders Micturition urgency	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Surgical and medical procedures Thyroidectomy	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Vascular disorders Arterial thrombosis limb	1.0% 1/99 • Number of events 1 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.

Other adverse events

Other adverse events
Measure	Neupro® Treatment n=99 participants at risk Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Gastrointestinal disorders Nausea	13.1% 13/99 • Number of events 15 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
General disorders Application site erythema	15.2% 15/99 • Number of events 17 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
General disorders Application site reaction	9.1% 9/99 • Number of events 9 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
General disorders Application site pruritus	8.1% 8/99 • Number of events 8 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
General disorders Fatigue	9.1% 9/99 • Number of events 9 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Nervous system disorders Headache	6.1% 6/99 • Number of events 6 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Psychiatric disorders Depression	5.1% 5/99 • Number of events 5 • Adverse Events were reported from Day 1 up to 13 months. The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.

Additional Information

UCB Clinical Trial Call Center

UCB

Phone: ++1 877 822 9493

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60