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

NCT04145674 | Suspended Phase 2

• 1 other identifier: NSI-RLS-001
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 4

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.

Conditions

Restless Legs Syndrome

Outcome Measures

Primary Outcomes (1)

• Efficacy of d-methadone

  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.

  30 days

Secondary Outcomes (4)

• Insomnia severity

  10 and 30 days

• Change in Quality of life

  10 and 30 days

• Periodic limb movements of sleep index

  10 days

• Actigrafic parameters

  10 and 30 days

Study Arms (2)

25 mg d-methadone

EXPERIMENTAL

The experimental drug is a tablet formulation of d-methadone HCl in dose strength of 25 mg.

Drug: D-methadone

Placebo

PLACEBO COMPARATOR

The placebo is an exact match to the active tablets in size, color and marking without the active ingredient d-methadone HCl.

Other: Placebo

Interventions

D-methadone DRUG

Patients will take one tablet of 25 mg d-methadone once daily at 6 pm over a period of 30 days

Also known as: esmethadone, dextromethadone, REL-1017

25 mg d-methadone

Placebo OTHER

Patients will take one tablet of placebo once daily at 6 pm over a period of 30 days

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mauro Manconi: lead
• Clinical Trial Unit Ente Ospedaliero Cantonale: collaborator

Study Sites (4)

Sleep Center, IRCCS San Raffaele

Milan, Italy

Location

Schlaf-Wach-Epilepsie Zentrum, Inselspital

Bern, Switzerland

Location

Neurologie / Schlaflabor Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Sleep Center, Neurocenter of Southern Switzerland

Lugano, 6900, Switzerland

Location

MeSH Terms

Conditions

Restless Legs Syndrome

Interventions

D-methadone

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Study Officials

• Mauro Manconi, Prof. MD

  Ente Ospedaliero Cantonale, Neurocenter of Southern Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. MD

Study Record Dates

• First Submitted: October 29, 2019
• First Posted: October 30, 2019
• Study Start: October 22, 2022
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

CH (3); IT (1)