Trial Outcomes & Findings for Switching From Oral Dopamine Agonists to Rotigotine (NCT NCT01976871)

Results Overview

The primary endpoint will be the safety and tolerability of switching from an oral dopamine agonist to rotigotine. The CGIC scales were developed to assess treatment outcomes in pharmacological studies. The scales are meant completed by the clinician in person after assessment of the subject. They include 4 global scales describing the severity of illness, change in severity from baseline, therapeutic efficacy, and tolerability of treatment. Clinical Global Impression - Improvement scale (CGI-I) rated as: 1, very much improved since the baseline week; 2, much improved; 3, minimally improved; 4, no change from baseline; 5, minimally worse; 6, much worse; or 7, very much worse since the baseline week. The CGI-I was performed at baseline and at Week 5 to see which participants rated as much or very much improved. Adverse Events are reported in the Adverse Events module.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

21 participants

Primary outcome timeframe

Participants will be monitored for the duration of the study, approximately 6-10 weeks depending upon scheduling of visits

Results posted on

2016-11-29

Participant Flow

Participant milestones

Participant milestones
Measure	Oral Dopamine Agonist to Rotigotine During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events. Rotigotine: Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
Overall Study STARTED	21
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Switching From Oral Dopamine Agonists to Rotigotine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oral Dopamine Agonist to Rotigotine n=20 Participants During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events. Rotigotine: Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants
Age, Continuous	66.0 years STANDARD_DEVIATION 12.1 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants

PRIMARY outcome

Timeframe: Participants will be monitored for the duration of the study, approximately 6-10 weeks depending upon scheduling of visits

The primary endpoint will be the safety and tolerability of switching from an oral dopamine agonist to rotigotine. The CGIC scales were developed to assess treatment outcomes in pharmacological studies. The scales are meant completed by the clinician in person after assessment of the subject. They include 4 global scales describing the severity of illness, change in severity from baseline, therapeutic efficacy, and tolerability of treatment. Clinical Global Impression - Improvement scale (CGI-I) rated as: 1, very much improved since the baseline week; 2, much improved; 3, minimally improved; 4, no change from baseline; 5, minimally worse; 6, much worse; or 7, very much worse since the baseline week. The CGI-I was performed at baseline and at Week 5 to see which participants rated as much or very much improved. Adverse Events are reported in the Adverse Events module.

Outcome measures

Outcome measures
Measure	Oral Dopamine Agonist to Rotigotine n=20 Participants During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events. Rotigotine: Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
Proportion of Patients Completing the Switch and Their Adverse Events Oral dopamine agonist to rotigotine switch success	17 participants
Proportion of Patients Completing the Switch and Their Adverse Events CGI-I responders (much or very much improved)	14 participants
Proportion of Patients Completing the Switch and Their Adverse Events Withdrew due to lack of efficacy	3 participants

SECONDARY outcome

Timeframe: Study Visit 1 (Day 1) and Study Visit 3 (approximately 35 days after initiating the switch from the oral dopamine agonist to the transdermal rotigotine)

The IRLS will be used to determine the overall efficacy of RLS symptom control on rotigotine. The IRLS is a well-validated instrument for measuring RLS severity during the past week. It includes 10 questions encompassing intensity and frequency of symptoms, associated sleep problems, and the impact of symptoms on the patients' mood and daily functioning. This scale has been shown to have high internal consistency, inter-examiner reliability, test-retest reliability, and convergent validity. Minimum score 0, maximum score 40. A decrease in the IRLS score indicates a better outcome.

Outcome measures

Outcome measures
Measure	Oral Dopamine Agonist to Rotigotine n=20 Participants During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events. Rotigotine: Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
International Restless Legs Scale (IRLS) Baseline (Day 1) IRLS score	19.4 units on a scale Standard Deviation 5.5
International Restless Legs Scale (IRLS) Week 5 IRLS score	12.7 units on a scale Standard Deviation 7.7

SECONDARY outcome

Timeframe: Average of Baseline titration week (approximately days 1-7 of the study) vs. Average of Final Treatment week (integrating data from days 28-35 after initiating the switch from the oral dopamine agonist to the transdermal rotigotine)

The RLS-6 scale will be used to determine the overall efficacy of RLS symptom control on rotigotine, calculated as a mean score for each scale during the final treatment week vs baseline. The RLS-6 scale are 11-point (0=not present to 10=very severe) metrics for measuring RLS severity. Four questions delineate a severity profile of RLS during different night and daytime periods: at bedtime, during the night, during the day at rest, during daily activities. The final two questions assess satisfaction with sleep and severity of sleepiness during the day. The RLS-6 scales have been validated on a day-to-day basis, with relatively low placebo effect compared to other RLS rating scales. Minimum score 0, maximum score 60. A decrease in the RLS-6 score indicates a better outcome. The RLS-6 scale was completed each day of the study and averaged for the baseline week (approximately days 1-7 of the study) and the final week (approximately days 21-28 of the maintenance period).

Outcome measures

Outcome measures
Measure	Oral Dopamine Agonist to Rotigotine n=20 Participants During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events. Rotigotine: Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
RLS-6 Scale Baseline RLS symptoms during the day at rest	2.8 units on a scale Standard Deviation 2.5
RLS-6 Scale Baseline RLS symptoms at bedtime	3.9 units on a scale Standard Deviation 3.2
RLS-6 Scale Week 5 RLS symptoms at bedtime	3.0 units on a scale Standard Deviation 3.1
RLS-6 Scale Baseline RLS symptoms during the night	2.5 units on a scale Standard Deviation 2.3
RLS-6 Scale Week 5 RLS symptoms during the night	2.1 units on a scale Standard Deviation 3.0
RLS-6 Scale Week 5 RLS symptoms during the day at rest	1.4 units on a scale Standard Deviation 2.4
RLS-6 Scale Baseline RLS symptoms during daily activities	1.4 units on a scale Standard Deviation 2.2
RLS-6 Scale Week 5 RLS symptoms during daily activities	0.9 units on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: Study Visit 1 (Day 1) and Study Visit 3 (approximately 35 days after initiating the switch from the oral dopamine agonist to the transdermal rotigotine)

The POM will be used to assess patient satisfaction with treatment. The POM scale is designed to summarize subjects' preference for the study medication compared to prior therapy. It asks a single question: "How does this current medicine compare to the previous RLS medicine(s) you were taking?" The response set is as follows: (1) Much Better, I prefer this medication (indicating preference for rotigotine); (2) Slightly Better; (3) About the Same; (4) Slightly Worse; (5) Much Worse, I much prefer my previous medication (indicating preference for oral dopamine agonist).

Outcome measures

Outcome measures
Measure	Oral Dopamine Agonist to Rotigotine n=20 Participants During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events. Rotigotine: Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
Preference of Medication Scale (POM) Much better, I prefer this med	13 participants
Preference of Medication Scale (POM) Slightly better	2 participants
Preference of Medication Scale (POM) About the same	0 participants
Preference of Medication Scale (POM) Slightly worse	2 participants
Preference of Medication Scale (POM) Much worse, I much prefer my previous med	3 participants

SECONDARY outcome

Timeframe: Study Visit 1 (Day 1) and Study Visit 3 (approximately 35 days after initiating the switch from the oral dopamine agonist to the transdermal rotigotine)

The Patient Global Impression of Change scale (PGIC) will be used to assess patient satisfaction with treatment. The PGIC assesses subjective changes in symptoms during clinical trials. This single-item scale asks participants to rate their symptoms as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." The measure provides a responsive and easily interpretable assessment of participants' evaluations of the importance of their improvement or worsening.

Outcome measures

Outcome measures
Measure	Oral Dopamine Agonist to Rotigotine n=20 Participants During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events. Rotigotine: Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
The Patient Global Impression of Change Scale Very much improved since baseline	12 participants
The Patient Global Impression of Change Scale Much improved	0 participants
The Patient Global Impression of Change Scale Minimally improved	3 participants
The Patient Global Impression of Change Scale No change from baseline	0 participants
The Patient Global Impression of Change Scale Minimally worse	2 participants
The Patient Global Impression of Change Scale Much worse	2 participants
The Patient Global Impression of Change Scale Very much worse since baseline	1 participants

SECONDARY outcome

Timeframe: Study Visit 1 (Day 1) and Study Visit 3 (approximately 35 days after initiating the switch from the oral dopamine agonist to the transdermal rotigotine)

The Clinician Global Impression of Change scale (CGIC) will be used to assess patient satisfaction with treatment.

Outcome measures

Outcome measures
Measure	Oral Dopamine Agonist to Rotigotine n=20 Participants During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events. Rotigotine: Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
The Clinician Global Impression of Change Scale Very much improved since baseline	10 participants
The Clinician Global Impression of Change Scale Much improved	4 participants
The Clinician Global Impression of Change Scale Minimally improved	1 participants
The Clinician Global Impression of Change Scale No change from baseline	0 participants
The Clinician Global Impression of Change Scale Minimally worse	1 participants
The Clinician Global Impression of Change Scale Much worse	4 participants
The Clinician Global Impression of Change Scale Very much worse since baseline	0 participants

Adverse Events

Oral Dopamine Agonist to Rotigotine

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Oral Dopamine Agonist to Rotigotine n=20 participants at risk During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events. Rotigotine: Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
Nervous system disorders Somnolence	45.0% 9/20 • 1 year
Nervous system disorders Worsening of RLS symptoms during cross-titration	30.0% 6/20 • 1 year
Skin and subcutaneous tissue disorders Skin reaction at patch application site	25.0% 5/20 • 1 year
Nervous system disorders Insomnia	15.0% 3/20 • 1 year
Gastrointestinal disorders Nausea	10.0% 2/20 • 1 year
Nervous system disorders Headache	10.0% 2/20 • 1 year
Nervous system disorders Fatigue	10.0% 2/20 • 1 year

Additional Information

Dr. John W. Winkelman

Massachusetts General Hospital

Phone: 617-643-9101

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60