Sublingual Apomorphine in Refractory Restless Legs Syndrome

Restless Legs Syndrome Clinical Trial

Official title:

Open Label and Placebo-Controlled Assessment of Sublingual Apomorphine (Kynmobi) as Adjunct Therapy for Patients With Refractory Restless Legs Syndrome

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05529095
• Other study ID #: PRO00033518
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 1, 2022
• Est. completion date: March 1, 2023

Study information

• Verified date: September 2022
• Source: The Methodist Hospital Research Institute
• Contact: William Ondo, MD
• Phone: 713-363-8184
• Email: wondo[@]houstonmethodist.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open label, short placebo-controlled trial in Restless Legs Syndrome (RLS) patients inadequately treated with standard therapy. Investigators hypothesize that the study drug, sublingual apomorphine (Kynmobi), may improve RLS breakthrough symptoms. This study is designed to determine if sublingual apomorphine improves breakthrough symptoms in RLS patients, in addition to subjective responses.

Description:

This is an open label, with a short placebo-controlled portion trial using sublingual apomorphine (Kynmobi) in RLS patients inadequately treated with standard therapy, defined by an IRLS > 15 and report of breakthrough symptoms.

At the initial visit, subjects will undergo all baseline and exploratory assessments and be given their first drug dose of 10 mg. They will be monitored for 60 minutes after dose. Subjects orthostatic blood pressure will be taken before ingestion, then 10, 20, 30, and 45 minutes after ingestion. Over the next 4 weeks, subjects will titrate Kynmobi to find optimal dose. Subjects will be instructed to take at least 2 doses before determining if further titration is needed.

At week 4, subjects will return for exploratory assessments. Subjects will be given a randomized study drug packet containing 2 placebos and 2 drug doses. Subjects will be told that 0-4 doses may be placebo or drug. Subjects will have 4 weeks to complete randomization doses. It is anticipated subjects will complete randomization sooner, so they will be given 23 doses of study drug (1 dose per 24 hours for 23 extra days until next visit).

At week 8, subjects will return for exploratory assessments and be given an additional 74 dosed strips. They will return at week 16 for a final visit and undergo exploratory assessments, followed by a safety call two weeks later.

From weeks 0-8, subjects are able to continue their scheduled RLS medications. From weeks 8-16, subjects may make changes to their RLS medications as mutually agreed upon with investigator.

Several questionnaire assessments will be conducted throughout the study to monitor subjects. Subjects will complete the International RLS Rating Scale (IRLS), Restless Legs Syndrome - 6 Scale (RLS - 6), RLS Quality of Life Questionnaire (RLSQoL), RLS Augmentation Scale, Fatigue Severity Scale (FSS), Hamilton Depression Scale (HDS), Clinical Global Impressions (CGI), and Clinical Global Impressions-Change (CGI-C).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 16
• Est. completion date: March 1, 2023
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

Inclusion Criteria:

• Idiopathic RLS diagnosed by standard criteria, with an IRLS > 15 while taking at least 1 RLS medication

• Stable RLS medications for at least 2 weeks prior to study entry

Exclusion Criteria:

• Concurrent untreated sleep disorders, not felt to be able stable

• Subjects with any significant, unstable cardiovascular, liver, lung, renal. psychiatric, or neurological diseases (not including RLS)

• Any medical or psychiatric comorbidity that, in the opinion of the investigator, would make study compliance difficult to achieve

• Intravenous iron within 4 weeks of study entry

• Breast feeding or pregnancy determined by urine pregnancy test in subjects where pregnancy is a possibility (pre-menopausal, sexually active women)

• Subjects with previous allergic reaction to apomorphine or sulfate sensitivity

• Subjects currently taking 5HT3 antagonists

Related Conditions & MeSH terms

• Psychomotor Agitation
• Restless Legs Syndrome
• Syndrome

Intervention

Drug:
• Apomorphine Sublingual Film
Sublingual Apomorphine initial dose 10 mg, titrated depending on symptomatic response.
• Placebo
Placebo (sugar pill)

Locations

Country	Name	City	State
United States	Houston Methodist Hospital	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
William Ondo, MD	Sunovion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Analogue Scale of Improvement	Subjects will assess how they feel 30 minutes after taking four doses of drug or placebo.	Weeks 4 - 8
Secondary	International RLS Rating Scale (IRLS)	This is a subjective scale to measure the severity of RLS within the past week.	Baseline, 4 weeks, 8 weeks, and 16 weeks
Secondary	The Restless Legs Syndrome - 6 Scale (RLS-6)	This scale measures the severity of daytime versus nighttime RLS symptoms.	Baseline, 4 weeks, 8 weeks, and 16 weeks
Secondary	Restless Legs Syndrome Quality of Life Questionnaire (RLSQoL)	This scale assess the quality of life in RLS patients.	Baseline, 4 weeks, 8 weeks, and 16 weeks
Secondary	Hamilton Depression Scale (HDS)	This scale assess symptoms of depression.	Baseline, 4 weeks, 8 weeks, and 16 weeks
Secondary	Epworth Sleepiness Scale (ESS)	This is a subjective scale that measures a patient's sleepiness.	Baseline, 4 weeks, 8 weeks, and 16 weeks
Secondary	Clinical Global Impressions - Change	This scale assess how much a patients illness has improved or worsened when compared to a baseline state from the beginning of the intervention.	1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, 12 weeks, 16 weeks, and 18-20 weeks