Restless Legs Syndrome
Conditions
Keywords
Rotigotine, Rotigotine nasal spray, Efficacy, safety and tolerability, Restless Legs Syndrome
Brief summary
The main objective of this phase 2a proof-of-concept trial is to assess the efficacy of rotigotine nasal spray in ascending doses in subjects with idiopathic Restless Legs Syndrome.
Detailed description
Each patient of the placebo and rotigotine group performed an Eligibility Assessment, as well 4 treatment days at which subjects performed a repeated 'Suggested Immobilization Test' (SIT) during a 30min pre-dose and a 4 hours post-dose period. During these periods the severity of RLS symptoms in the legs was assessed by the subject using a numeric symptom severity scale. In addition the leg movements were measured by actigraphy to assess the Periodic Leg Movement Index during Wakefulness (PLMWI, PLM per hour). Subjects applied a single dose of treatment on each treatment day (placebo nasal spray or rotigotine nasal spray in 3 ascending doses).
Interventions
Daily single dose of 62µg, 124µg, and 247µg rotigotine delivered as single puff of nasal spray solution
OTHERPlacebo Nasal Spray
Daily single dose of placebo delivered as single puff of nasal spray solution
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with idiopathic RLS, who are responding to an ongoing L-dopa treatment
Exclusion criteria
* Patients with secondary RLS or clinically relevant concomitant diseases or medical conditions are excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo | 4 hours post-treatment period at each treatment day | Subjects rate the severity of the RLS symptoms at the start of each pre dose and post dose Suggested Immobilization Test (SIT-0 to SIT-6) and every 5min during each SIT, using a numeric symptoms severity scale, where 0=not severe and 10=very severe. |
| Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo. | 4 hours post-treatment period at each treatment day | The Periodic Limb Movement (PLM) during Wakefulness Index (PLMWI) measures the number of limb movements per hour and indicates the frequency of PLMs when the subject is awake and the degree of motor symptoms of the disorder during wake time. No movements would result in a score of 0 PLM per hour. Outcome is the average movements per hour in the 4 hour post-dose period per subject. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects receiving a single dose of placebo nasal spray on all 4 treatment days | 10 |
| Rotigotine Nasal Spray Subjects receiving doses of placebo nasal spray on Day 1 or Day 2, Rotigotine nasal spray 62µg on Day 1 or Day 2, Rotigotine nasal spray 124µg on Day 3, and Rotigotine nasal spray 247µg on Day 4 | 34 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive treatment. | 0 | 2 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other reasons | 0 | 2 |
Baseline characteristics
| Characteristic | Rotigotine Nasal Spray | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants | 9 Participants | 42 Participants |
| Age, Continuous | 52.9 years STANDARD_DEVIATION 7.78 | 55.5 years STANDARD_DEVIATION 5.4 | 53.5 years STANDARD_DEVIATION 7.33 |
| Region of Enrollment Germany | 34 participants | 10 participants | 44 participants |
| Sex: Female, Male Female | 21 Participants | 8 Participants | 29 Participants |
| Sex: Female, Male Male | 13 Participants | 2 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 10 | 3 / 10 | 2 / 10 | 2 / 10 | 16 / 31 | 14 / 31 | 10 / 28 | 11 / 28 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 31 | 0 / 31 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo
Subjects rate the severity of the RLS symptoms at the start of each pre dose and post dose Suggested Immobilization Test (SIT-0 to SIT-6) and every 5min during each SIT, using a numeric symptoms severity scale, where 0=not severe and 10=very severe.
Time frame: 4 hours post-treatment period at each treatment day
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Day 1 | Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo | 2.6 score on a scale | Standard Deviation 1.76 |
| Placebo - Day 2 | Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo | 2.2 score on a scale | Standard Deviation 1.44 |
| Placebo - Day 3 | Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo | 2.5 score on a scale | Standard Deviation 2.03 |
| Placebo - Day 4 | Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo | 2.0 score on a scale | Standard Deviation 1.65 |
| Rotigotine Nasal Spray - Placebo | Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo | 2.9 score on a scale | Standard Deviation 1.99 |
| Rotigotine Nasal Spray - Rotigotine 62µg | Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo | 2.7 score on a scale | Standard Deviation 1.84 |
| Rotigotine Nasal Spray - Rotigotine 124µg | Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo | 2.0 score on a scale | Standard Deviation 1.14 |
| Rotigotine Nasal Spray - Rotigotine 247µg | Average Numeric Symptom Severity Score After Single Dose of Rotigotine Nasal Spray or Matching Placebo | 1.5 score on a scale | Standard Deviation 1.21 |
Primary
Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo.
The Periodic Limb Movement (PLM) during Wakefulness Index (PLMWI) measures the number of limb movements per hour and indicates the frequency of PLMs when the subject is awake and the degree of motor symptoms of the disorder during wake time. No movements would result in a score of 0 PLM per hour. Outcome is the average movements per hour in the 4 hour post-dose period per subject.
Time frame: 4 hours post-treatment period at each treatment day
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Day 1 | Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo. | 37.8 PLM per hour | Standard Deviation 35.1 |
| Placebo - Day 2 | Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo. | 22.6 PLM per hour | Standard Deviation 28.36 |
| Placebo - Day 3 | Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo. | 34.9 PLM per hour | Standard Deviation 39.78 |
| Placebo - Day 4 | Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo. | 19.0 PLM per hour | Standard Deviation 23.6 |
| Rotigotine Nasal Spray - Placebo | Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo. | 28.7 PLM per hour | Standard Deviation 29.91 |
| Rotigotine Nasal Spray - Rotigotine 62µg | Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo. | 25.4 PLM per hour | Standard Deviation 25.14 |
| Rotigotine Nasal Spray - Rotigotine 124µg | Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo. | 26.2 PLM per hour | Standard Deviation 22.78 |
| Rotigotine Nasal Spray - Rotigotine 247µg | Average PLMWI (Periodic Leg Movement Index During Wakefulness) After Single Dose of Rotigotine Nasal Spray or Matching Placebo. | 20.2 PLM per hour | Standard Deviation 21.7 |