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

Mauro Manconi

Status and phase: Enrolling; Phase 2

Conditions: Restless Legs Syndrome

Treatments: Other: Placebo; Drug: D-methadone

Study type: Interventional

Funder types: Other

Identifiers

NCT04145674

NSI-RLS-001

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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50 participants in 2 patient groups, including a placebo group

25 mg d-methadone

Experimental group

Description:

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

Treatment:

Drug: D-methadone

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo