Restless Legs Syndrome
Conditions
Keywords
RLS, Neupro, Rotigotine
Brief summary
The purpose of this study is to assess the long-term safety, tolerability and the long-term efficacy of rotigotine treatment in adolescents with idiopathic Restless Legs Syndrome (RLS).
Interventions
DRUGRotigotine 1 mg/24 h
Pharmaceutical Form: transdermal patch Route of administration: transdermal use Concentration: Application of rotigotine transdermal patch with 1 mg/24 h (5 cm\^2 patch size).
DRUGRotigotine 2 mg/24 h
Pharmaceutical Form: transdermal patch Route of administration: transdermal use Concentration: Application of rotigotine transdermal patch with 2 mg/24 h (10 cm\^2 patch size).
DRUGRotigotine 3 mg/24 h
Pharmaceutical Form: transdermal patch Route of administration: transdermal use Concentration: Application of rotigotine transdermal patch with 3 mg/24 h (15 cm\^2 patch size).
Sponsors
UCB Biopharma SRL
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subject weighs \>=40 kg * Subject has completed at least one dose step in SP1006, a previous study of rotigotine in adolescents with Restless Legs Syndrome (RLS), without meeting withdrawal criteria * 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 drug * Subject is expected to benefit from participation, in the opinion of the investigator
Exclusion criteria
* Subject is experiencing an ongoing serious Adverse Event (SAE) that is assessed to be related to rotigotine by the investigator or Sponsor * Subject has active suicidal ideation as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Since Last Visit version of the electronic Columbia Suicide Severity Rating Scale (eC-SSRS) at the final evaluation visit of the previous rotigotine study (ie, Visit 10 of SP1006)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | From Baseline until the Safety Follow-Up Visit (up to 14 Months) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (ie, 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 Withdrawal of Study Medication | From Baseline until the Safety Follow-Up Visit (up to 14 Months) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (ie, 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 |
|---|---|---|
| Changes From Baseline in International Restless Legs Rating Scale (IRLS) Sum Score at Visit 9 | Visit 9 (Month 12), compared to Baseline (in SP1006) | 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. |
| Changes From Baseline in Clinical Global Impressions (CGI) Item 1 at Visit 9 | Visit 9 (Month 12), compared to Baseline (in SP1006) | 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. |
| Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Visit 9 (Month 12), compared to Baseline (in SP1006) | 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 (not at rest). 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 2019 and concluded prematurely in September 2022. Study participants entered this study from the parent rotigotine study in adolescents (SP1006) (NCT03728933).
Pre-assignment details
10 participants were screened and considered enrolled, but only 9 participants were treated. The 10th participant was lost to follow-up prior dosing and no Adverse events were reported for this participant. Participant Flow refers to the Enrolled Set.
Participants by arm
| Arm | Count |
|---|---|
| Rotigotine Final Dose 2 mg/24 h Participants in this arm were initiated on 1 mg/24 h rotigotine and up-titrated to a maximum of 2 mg/24 h rotigotine and the same dose was continued throughout the 1 year Maintenance Period. Dose adjustment was allowed at any time during the Maintenance Period, based on the investigator's assessment. At the end of the Maintenance Period, participants were down-titrated. | 2 |
| Rotigotine Final Dose 3 mg/24 h Participants in this arm were initiated on 1 mg/24 h rotigotine and up-titrated to a maximum of 3 mg/24 h rotigotine and the same dose was continued throughout the 1 year Maintenance Period. Dose adjustment was allowed at any time during the Maintenance Period, based on the investigator's assessment. At the end of the Maintenance Period, participants were down-titrated. | 7 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Enrollment | lost to follow-up prior dosing | 1 | 0 | 0 |
| Treatment | PI's decision due to investigational medicinal product non-compliance | 0 | 0 | 1 |
| Treatment | Poor drug compliance withdrawn by team and sponsor | 0 | 0 | 1 |
| Treatment | Protocol Violation | 0 | 0 | 1 |
| Treatment | Withdrawal by parent/guardian | 0 | 0 | 2 |
| Treatment | Withdrawal due to non-compliance | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Rotigotine Final Dose 2 mg/24 h | Rotigotine Final Dose 3 mg/24 h | Total |
|---|---|---|---|
| Age, Customized Adolescents (12-17 years) | 2 Participants | 7 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 2 Participants | 7 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 5 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 7 |
| other Total, other adverse events | 2 / 2 | 6 / 7 |
| serious Total, serious adverse events | 0 / 2 | 0 / 7 |
Outcome results
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (ie, 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 until the Safety Follow-Up Visit (up to 14 Months)
Population: The Safety Set consisted of all participants who had at least one patch (rotigotine) applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotigotine Final Dose 2 mg/24 h | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 100 percentage of participants |
| Rotigotine Final Dose 3 mg/24 h | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 85.7 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal of Study Medication
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (ie, 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 until the Safety Follow-Up Visit (up to 14 Months)
Population: The Safety Set consisted of all participants who had at least one patch (rotigotine) applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotigotine Final Dose 2 mg/24 h | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal of Study Medication | 0 percentage of participants |
| Rotigotine Final Dose 3 mg/24 h | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal of Study Medication | 0 percentage of participants |
Secondary
Changes From Baseline in Clinical Global Impressions (CGI) Item 1 at Visit 9
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: Visit 9 (Month 12), compared to Baseline (in SP1006)
Population: The Safety Set consisted of all participants who had at least one patch (rotigotine) applied. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rotigotine Final Dose 2 mg/24 h | Changes From Baseline in Clinical Global Impressions (CGI) Item 1 at Visit 9 | NA score on a scale |
| Rotigotine Final Dose 3 mg/24 h | Changes From Baseline in Clinical Global Impressions (CGI) Item 1 at Visit 9 | NA score on a scale |
Secondary
Changes From Baseline in International Restless Legs Rating Scale (IRLS) Sum Score at Visit 9
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: Visit 9 (Month 12), compared to Baseline (in SP1006)
Population: The Safety Set consisted of all participants who had at least one patch (rotigotine) applied. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rotigotine Final Dose 2 mg/24 h | Changes From Baseline in International Restless Legs Rating Scale (IRLS) Sum Score at Visit 9 | NA score on a scale |
| Rotigotine Final Dose 3 mg/24 h | Changes From Baseline in International Restless Legs Rating Scale (IRLS) Sum Score at Visit 9 | NA score on a scale |
Secondary
Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9
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 (not at rest). 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: Visit 9 (Month 12), compared to Baseline (in SP1006)
Population: The Safety Set consisted of all participants who had at least one patch (rotigotine) applied. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Rotigotine Final Dose 2 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Satisfaction with sleep | NA score on a scale |
| Rotigotine Final Dose 2 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Severity: RLS symptoms at falling asleep | NA score on a scale |
| Rotigotine Final Dose 2 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Severity: RLS symptoms during the night | NA score on a scale |
| Rotigotine Final Dose 2 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Severity: RLS symptoms during the day - at rest | NA score on a scale |
| Rotigotine Final Dose 2 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Severity: RLS symptoms during the day-not at rest | NA score on a scale |
| Rotigotine Final Dose 2 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | How tired or sleepy during the day | NA score on a scale |
| Rotigotine Final Dose 3 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Severity: RLS symptoms during the day-not at rest | NA score on a scale |
| Rotigotine Final Dose 3 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Satisfaction with sleep | NA score on a scale |
| Rotigotine Final Dose 3 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Severity: RLS symptoms during the day - at rest | NA score on a scale |
| Rotigotine Final Dose 3 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Severity: RLS symptoms at falling asleep | NA score on a scale |
| Rotigotine Final Dose 3 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | How tired or sleepy during the day | NA score on a scale |
| Rotigotine Final Dose 3 mg/24 h | Changes From Baseline in Restless Legs-6 Rating Scales (RLS-6) at Visit 9 | Severity: RLS symptoms during the night | NA score on a scale |