Restless Legs Syndrome
Conditions
Keywords
RLS, Rotigotine, Neupro
Brief summary
The purpose of this study is to demonstrate the efficacy of rotigotine against placebo in adolescent subjects with idiopathic Restless Legs Syndrome (RLS) over a 12-week maintenance period and to investigate the safety and tolerability of rotigotine in adolescent subjects with idiopathic RLS.
Interventions
DRUGRotigotine 1 milligram/24 hours
Pharmaceutical Form: transdermal patch Route of administration: transdermal use Concentration: Application of rotigotine transdermal patch with 1 milligram (mg)/24 hours (h) (5 square centimeter (cm\^2) patch size).
DRUGRotigotine 2 milligram/24 hours
Pharmaceutical Form: transdermal patch Route of administration: transdermal use Concentration: Application of rotigotine transdermal patch with 2 milligram (mg)/24 hours (h) (10 square centimeter (cm\^2) patch size).
DRUGPlacebo
Pharmaceutical Form: transdermal patch Route of administration: transdermal use Concentration: not applicable
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subject is male or female, and is \>=13 and \<18 years of age at Baseline * Subject's Restless Legs Syndrome (RLS) symptoms cause significant daytime symptoms or significant distress or impairment in social, occupational, educational, or other important areas of functioning by the impact on sleep, energy/vitality, daily activities, behavior, cognition or mood * At Baseline, subject has a score of \>=15 on the International Restless Legs Rating Scale (IRLS) (indicating moderate-to-severe RLS) * At Baseline, subject scores \>=4 points on the Clinical Global Impressions (CGI) Item 1 assessment (indicating at least moderately ill) * Subjects who are receiving supplemental iron have been on a stable dose for at least 1 month prior to Screening * Female subjects must be surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and spermicide). Abstinence is an acceptable method. Subjects must agree to use adequate contraception during the study and for 4 weeks after their final dose of study medication.
Exclusion criteria
* Subject has a serum ferritin level below the lower limit of normal at Visit 1/Screening * Subject has a hemoglobin level below the lower limit of normal at Visit 1/Screening * Subject has had previous treatment with dopamine agonists or L-dopa within 7 days prior to Visit 2/Baseline * Subject has any medical or psychiatric condition, which in the opinion of the investigator, would jeopardize or compromise the subject's well-being or ability to participate in this study * Subject is pregnant or nursing * Subject is not willing to abstain from caffeine after 4 pm each evening within 7 days prior to Visit 2/Baseline and for the duration of the study * At Visit 1/Screening, subject has symptomatic orthostatic hypotension with a decrease of blood pressure (BP) from supine to standing position of \>=20 mmHg in systolic blood pressure (SBP) or of \>=10 mmHg in diastolic * Subject has secondary Restless Legs Syndrome (RLS) (eg, due to renal insufficiency \[uremia\], iron deficiency, or rheumatoid arthritis) * Subject has a lifetime history of suicide attempts (including actual attempt, interrupted attempt, or aborted attempt), or had suicidal ideation in the past 6 months as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 1) * Subject is taking a prohibited concomitant medication. Prohibited concomitant medication must have been discontinued at least 2 weeks prior to Screening (Visit 1)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End of the Maintenance Period in International Restless Legs Rating Scale (IRLS) Sum Score | From Baseline to the end of the Maintenance Period (Day 106) | The IRLS consisted of 10 questions, each scored using a 5-point scale ranging from 0=not present to 4=very severe. The IRLS sum score was calculated by summing up the single scores of all applicable questions, i.e., the total sum score ranged from 0 (no RLS symptoms present) to 40 (maximum severity in all symptoms). A score between 31 and 40, indicates very severe RLS. A score between 21 and 30 indicates severe RLS. A score between 11 and 20 indicates moderate RLS. A score between 1 and 10 indicates mild RLS and a score of 0 means no RLS. A negative change from Baseline indicates improvement. |
| Change From Baseline in Clinical Global Impressions (CGI) Item 1 to the End of the Maintenance Period | From Baseline to the end of the Maintenance Period (Day 106) | The Clinical Global Impressions Item 1 (Severity of Illness) score ranges from 0 to 7 as follows: 0=not assessed, 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. The CGI Item 1 was completed during an interview between the participant and the investigator or designee. A negative change from Baseline indicates improvement. |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | From Baseline to Safety Follow-Up (up to Week 20) | TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (i.e., on or after the date of first patch application and within 30 days following the date of last patch removal + 1 day), or those events where the intensity worsened within this time frame. |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawals | From Baseline to Safety Follow-Up (up to Week 20) | TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (i.e., on or after the date of first patch application and within 30 days following the date of last patch removal + 1 day), or those events where the intensity worsened within this time frame. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | From Baseline to the end of the Maintenance Period (Day 106) | The RLS-6 Rating Scales was designed to assess the severity of RLS and consisted of 6 subscales. The subscales assessed severity of symptoms at the following times of the day/evening: falling asleep, during the night, during the day at rest, and during the day when engaged in daytime activities. In addition, the subscales assessed satisfaction with sleep and severity of daytime tiredness/sleepiness. Scores for each of the 6 subscales ranged from 0 (completely satisfied) to 10 (completely dissatisfied). The change from baseline was derived for each of the subscales and reported in this outcome measure. A negative change from Baseline indicates improvement. |
Countries
United States
Participant flow
Recruitment details
The study started to enroll participants in December 2018 and concluded prematurely in July 2022.
Pre-assignment details
The Participant Flow refers to the Randomized Set.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to this arm received placebo as a comparator matched to rotigotine during 3 week titration period and is continued throughout the 12-week Maintenance Period. | 8 |
| Rotigotine 2 mg/24h Participants randomized to this arm were initiated on 1 mg/24 h rotigotine and up-titrated to a maximum of 2 mg/24 h rotigotine during 3 week titration period and the same dose is continued throughout the 12-week Maintenance Period. | 8 |
| Rotigotine 3 mg/24h Participants randomized to this arm were initiated on 1 mg/24 h rotigotine and up-titrated to a maximum of 3 mg/24 h rotigotine during 3 week titration period and the same dose is continued throughout the 12-week Maintenance Period. | 7 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Withdrawal by Parent/Guardian | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Rotigotine 2 mg/24h | Rotigotine 3 mg/24h |
|---|---|---|---|---|
| Age, Continuous | 15.7 years STANDARD_DEVIATION 1.1 | 15.4 years STANDARD_DEVIATION 1.3 | 16.1 years STANDARD_DEVIATION 1.1 | 15.6 years STANDARD_DEVIATION 1 |
| Age, Customized Adolescents (12-17 years) | 23 Participants | 8 Participants | 8 Participants | 7 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 23 Participants | 8 Participants | 8 Participants | 7 Participants |
| Race/Ethnicity, Customized Other/Mixed | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 20 Participants | 7 Participants | 7 Participants | 6 Participants |
| Sex: Female, Male Female | 14 Participants | 6 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Male | 9 Participants | 2 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 7 / 8 | 7 / 8 | 5 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 1 / 7 |
Outcome results
Primary
Change From Baseline in Clinical Global Impressions (CGI) Item 1 to the End of the Maintenance Period
The Clinical Global Impressions Item 1 (Severity of Illness) score ranges from 0 to 7 as follows: 0=not assessed, 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. The CGI Item 1 was completed during an interview between the participant and the investigator or designee. A negative change from Baseline indicates improvement.
Time frame: From Baseline to the end of the Maintenance Period (Day 106)
Population: The FAS consisted of all participants from the Safety Set who had a valid IRLS score and a valid CGI Item 1 score at Baseline and a valid post-Baseline IRLS score and a valid post-Baseline CGI Item 1 score. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Clinical Global Impressions (CGI) Item 1 to the End of the Maintenance Period | -1.0 score on a scale | Standard Deviation 1.4 |
| Rotigotine 2 mg/24h | Change From Baseline in Clinical Global Impressions (CGI) Item 1 to the End of the Maintenance Period | -1.7 score on a scale | Standard Deviation 1.1 |
| Rotigotine 3 mg/24h | Change From Baseline in Clinical Global Impressions (CGI) Item 1 to the End of the Maintenance Period | -0.8 score on a scale | Standard Deviation 0.8 |
Primary
Change From Baseline to the End of the Maintenance Period in International Restless Legs Rating Scale (IRLS) Sum Score
The IRLS consisted of 10 questions, each scored using a 5-point scale ranging from 0=not present to 4=very severe. The IRLS sum score was calculated by summing up the single scores of all applicable questions, i.e., the total sum score ranged from 0 (no RLS symptoms present) to 40 (maximum severity in all symptoms). A score between 31 and 40, indicates very severe RLS. A score between 21 and 30 indicates severe RLS. A score between 11 and 20 indicates moderate RLS. A score between 1 and 10 indicates mild RLS and a score of 0 means no RLS. A negative change from Baseline indicates improvement.
Time frame: From Baseline to the end of the Maintenance Period (Day 106)
Population: The Full Analysis Set (FAS) consisted of all participants from the Safety Set who had a valid IRLS score and a valid clinical global impressions (CGI) Item 1 score at Baseline and a valid post-Baseline IRLS score and a valid post-Baseline CGI Item 1 score. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of the Maintenance Period in International Restless Legs Rating Scale (IRLS) Sum Score | -8.2 score on a scale | Standard Deviation 6.8 |
| Rotigotine 2 mg/24h | Change From Baseline to the End of the Maintenance Period in International Restless Legs Rating Scale (IRLS) Sum Score | -14.0 score on a scale | Standard Deviation 8.2 |
| Rotigotine 3 mg/24h | Change From Baseline to the End of the Maintenance Period in International Restless Legs Rating Scale (IRLS) Sum Score | -6.4 score on a scale | Standard Deviation 5.8 |
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (i.e., on or after the date of first patch application and within 30 days following the date of last patch removal + 1 day), or those events where the intensity worsened within this time frame.
Time frame: From Baseline to Safety Follow-Up (up to Week 20)
Population: The Safety Set consisted of all participants from the Randomized Set (RS) who had at least one patch (rotigotine or placebo) applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 87.5 percentage of participants |
| Rotigotine 2 mg/24h | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 87.5 percentage of participants |
| Rotigotine 3 mg/24h | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 71.4 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawals
TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (i.e., on or after the date of first patch application and within 30 days following the date of last patch removal + 1 day), or those events where the intensity worsened within this time frame.
Time frame: From Baseline to Safety Follow-Up (up to Week 20)
Population: The Safety Set consisted of all participants from the RS who had at least one patch (rotigotine or placebo) applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawals | 12.5 percentage of participants |
| Rotigotine 2 mg/24h | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawals | 0 percentage of participants |
| Rotigotine 3 mg/24h | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawals | 0 percentage of participants |
Secondary
Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period
The RLS-6 Rating Scales was designed to assess the severity of RLS and consisted of 6 subscales. The subscales assessed severity of symptoms at the following times of the day/evening: falling asleep, during the night, during the day at rest, and during the day when engaged in daytime activities. In addition, the subscales assessed satisfaction with sleep and severity of daytime tiredness/sleepiness. Scores for each of the 6 subscales ranged from 0 (completely satisfied) to 10 (completely dissatisfied). The change from baseline was derived for each of the subscales and reported in this outcome measure. A negative change from Baseline indicates improvement.
Time frame: From Baseline to the end of the Maintenance Period (Day 106)
Population: The FAS consisted of all participants from the Safety Set who had a valid IRLS score and a valid CGI Item 1 score at Baseline and a valid post-Baseline IRLS score and a valid post-Baseline CGI Item 1 score. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms at falling asleep | -2.8 score on a scale | Standard Deviation 3.6 |
| Placebo | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | How tired or sleepy during the day | -3.0 score on a scale | Standard Deviation 2.8 |
| Placebo | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Satisfaction with sleep | -1.8 score on a scale | Standard Deviation 4.1 |
| Placebo | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms during the night | -1.0 score on a scale | Standard Deviation 2.5 |
| Placebo | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms during the day - at rest | -1.4 score on a scale | Standard Deviation 1.3 |
| Placebo | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms during the day-not at rest | -3.8 score on a scale | Standard Deviation 1.9 |
| Rotigotine 2 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms during the day - at rest | -3.6 score on a scale | Standard Deviation 3.5 |
| Rotigotine 2 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms during the day-not at rest | -4.3 score on a scale | Standard Deviation 3.5 |
| Rotigotine 2 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms at falling asleep | -5.6 score on a scale | Standard Deviation 1.6 |
| Rotigotine 2 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms during the night | -2.9 score on a scale | Standard Deviation 3 |
| Rotigotine 2 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | How tired or sleepy during the day | -5.6 score on a scale | Standard Deviation 2.1 |
| Rotigotine 2 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Satisfaction with sleep | -4.7 score on a scale | Standard Deviation 2.3 |
| Rotigotine 3 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | How tired or sleepy during the day | -3.0 score on a scale | Standard Deviation 1.9 |
| Rotigotine 3 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms at falling asleep | -2.8 score on a scale | Standard Deviation 1.8 |
| Rotigotine 3 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms during the night | -2.4 score on a scale | Standard Deviation 2.2 |
| Rotigotine 3 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms during the day - at rest | -2.4 score on a scale | Standard Deviation 2.6 |
| Rotigotine 3 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Severity: RLS symptoms during the day-not at rest | -0.4 score on a scale | Standard Deviation 1.1 |
| Rotigotine 3 mg/24h | Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period | Satisfaction with sleep | -2.0 score on a scale | Standard Deviation 2.8 |