A Proof of Concept, Phase 2, Double-blind, Randomized Trial With d-Methadone Product Versus Placebo

Phase 2

Recruiting

• Conditions: Restless Legs Syndrome
• Interventions: Other: Placebo; Drug: D-methadone

• Registration Number: NCT04145674
• Lead Sponsor: Mauro Manconi

Brief Summary

Proof of concept, double-blind, randomized, placebo-controlled trial with d-methadone proposed for the first time for use in the treatment of patients diagnosed with primary, moderate to very severe Restless Legs Syndrome (RLS). Its glutamatergic mechanism of action might be effective on RLS arousal pattern and sleep disturbance which highly impair the quality of life of RLS's patients.

Patients will take the study drug/placebo once a day for 30 consecutive days.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-29
• Study First Submitted QC: 2019-10-29
• Study First Posted: 2019-10-30
• Study Start: 2022-10-22
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-29
• Last Update Posted: 2024-03-01
• Primary Completion: 2025-07-30
• Study Completion: 2025-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Diagnosis of primary RLS.
• Moderate to very severe RLS defined as IRLS-RS score > 10.
• Written informed consent.
• Willingness and ability to participate in the trial

Exclusion Criteria

• Positive history of known causes of secondary RLS.
• Any other concomitant treatment for RLS (wash-out period: at least 7 days).
• Moderate-severe sleep apnea defined as Apnea Hypopnea Index ≥ 15.
• History or presence of clinically significant abnormality as assessed by neurological examination which in the opinion of the Investigator would jeopardize the safety of the patients or the validity of the study results.
• Evidence of clinically significant hepatic or renal impairment
• History or family history of sudden unexplained death or long QT syndrome.
• Any 12-lead ECG with demonstration of QTc ≥ 450 msec or a QRS interval ≥ 120 msec at Screening.
• Concomitant use of psycho-drugs dopamine agonists and opioids (wash-out period: at least 7 days).
• History or presence of any condition in which an opioid is contraindicated
• History of allergy or hypersensitivity to methadone or related drugs.
• Any clinically significant neurological, sleep, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, chronic pain, psychiatric or gastrointestinal disorder.
• Women who are pregnant or breast feeding.
• Inability to follow the procedures of the study, (e.g. due to language problems, psychological disorders, dementia, etc. of the participant).
• Previous enrolment into the current study.
• Enrolment of the investigator, his/her family members, employees and other dependent persons.
• Participation in another study with investigational drug within the 30 days preceding and during the present study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	The placebo is an exact match to the active tablets in size, color and marking without the active ingredient d-methadone HCl.
25 mg d-methadone	D-methadone	The experimental drug is a tablet formulation of d-methadone HCl in dose strength of 25 mg.

Primary Outcome Measures

Name	Time	Method
Efficacy of d-methadone	30 days	The percentage of responders to d-methadone treatment. A responder is defined as patient who has ≥ 50% reduction in the International RLS Rating Scale (IRLS-RS) score from baseline to end of the 30-day treatment period.

Secondary Outcome Measures

Name	Time	Method
Insomnia severity	10 and 30 days	Change in insomnia severity from baseline to the end of 10-day dosing period and to end of the treatment period assessed by a using the Insomnia Severity Index (ISI)
Change in Quality of life	10 and 30 days	Change in quality of life from baseline to the end of 10-day dosing period and to end of the treatment period assessed assessed by a using the Restless Legs Syndrome Quality of Life Questionnaire (RLSQoL)
Periodic limb movements of sleep index	10 days	Change in Periodic limb movements of sleep (PLMS) index from baseline to end of 10-day dosing period measured by means of polysomnography recording
Actigrafic parameters	10 and 30 days	Change from baseline to the end of 10-day dosing period and to end of the treatment period on Total Sleep Time, Sleep Latency and Sleep Efficacy acquired assessed by actigraphy with measurements performed one week prior to the start of treatment, during the 10-day dosing period and one week at the end of the treatment.

Trial Locations

Locations (4)

Sleep Center, IRCCS San Raffaele; 🇮🇹 Milan, Italy

Schlaf-Wach-Epilepsie Zentrum, Inselspital; 🇨🇭 Bern, Switzerland

Neurologie / Schlaflabor Kantonsspital Graubünden; 🇨🇭 Chur, Switzerland

Sleep Center, Neurocenter of Southern Switzerland; 🇨🇭 Lugano, Switzerland