Treatment of Restless Leg Syndrome (RLS) Augmentation With Ecopipam, a D1 Specific Antagonist

NCT03218969 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Pro#00016705
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is an exploratory, double blinded cross-over study of the D1 antagonist ecopipam treat patients currently having dopamine agonist induced augmentation in restless legs syndrome. Each arm is 6 weeks composed of an unforced titration up to 100mg/day separated by a 2-week wash-out period. Efficacy points will include the IRLS, augmentation scales, sleep scales, clinical impressions and fatigue/mood scales.

Conditions

Restless Legs Syndrome; Augmentation

Outcome Measures

Primary Outcomes (2)

• Change From Baseline (Predose) in Mean International Restless Legs Syndrome (IRLS) Rating Scale at End of Intervention Period

  IRLS scale is a patient-administered test that measures the severity of restless legs syndrome symptoms. The IRLS scale consists of 10 questions rated from 0 to 4. The total score on symptom severity range from 0 (none) to 40 (worst).

  Baseline (Pre-intervention), and at 5 weeks

• Change From Baseline in Mean Body Part Affected by RLS Symptoms Using Augmentation Severity Rating Scale (ASRS)

  ASRS scale has three items and probes symptoms over the past week. The first item asks the time at which symptoms began in the last week. The second item probes how quickly symptoms begin when sitting at various times of the day during the past week, and the third item probes which body parts were involved in the past week. Each item has a total of 8 points for a 24-point total scale. 0 is no augmentation and 24 is the most severe augmentation. In the third item, participants are asked to shade in the figure the portions of his/her body affected by RLS symptoms for a total of 8 points. The higher the score the worse the outcome

  Baseline (Pre-intervention), and at 5 weeks

Secondary Outcomes (2)

• Mean 24 Hour Restless Legs Syndrome (RLS) Diary at End of Intervention

  at end of intervention Ecopipam, at end of intervention Placebo

• Number of Participants With Effect on the Clinical Global Impression Scale at the End of the Intervention

  At end of intervention Ecopipam, at end of intervention Placebo

Other Outcomes (2)

• Change in Mean From Baseline Epworth Sleep Scale (ESS) at the End of the Intervention

  Baseline (Pre-intervention), and at Week 5

• Change in Mean Score From Baseline Montreal Cognitive Assessment (MoCA) at End of Intervention

  Baseline (Pre-intervention), and at Week 5

Study Arms (2)

Study period 1

EXPERIMENTAL

* Ecopipam or matching placebo 25 mg by mouth for 7 days (week 1), followed by * Ecopipam or matching placebo 50 mg by mouth for 7 days (week 2), followed by * Ecopipam or matching placebo 100 mg by mouth for 23 days (weeks 3).

Drug: Ecopipam; Drug: Placebo

Study period 2

EXPERIMENTAL

* Matching placebo or ecopipam 25 mg by mouth for 7 days (week 7), followed by * Matching placebo or ecopipam 50 mg by mouth for 7 days (week 8), followed by * Matching placebo or ecopipam 100 mg by mouth for 23 days (week 9).

Drug: Ecopipam; Drug: Placebo

Interventions

Ecopipam DRUG

oral drug in subjection currently experiencing dopamine agonist induced augmentation

Also known as: PSYRX101

Study period 1; Study period 2

Placebo DRUG

matching placebo

Study period 1; Study period 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide consent to participate in the study
• Individuals of either sex, 21-80 years of age
• Clinically defined Restless Leg Syndrome, and problematic augmentation currently on monotherapy with dopaminergic treatment.

You may not qualify if:

• Current use of Opioid medications
• Clinical relevant depression or other medical problems that in the opinion of the investigator would not allow for safe completion of the protocol.
• Suicidal ideation
• History of epilepsy
• Current MAO inhibitors

Sponsors & Collaborators

• William Ondo, MD: lead
• Restless Legs Syndrome Foundation: collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Restless Legs Syndrome

Interventions

ecopipam

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: William Ondo, MD
• Organization: Methodist Neurological Institute

wondo@houstonmethodist.org

713-363-8484

Study Officials

• William G. Ondo, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: placebo
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 21, 2017
• First Posted: July 17, 2017
• Study Start: September 18, 2017
• Primary Completion: September 28, 2018
• Study Completion: November 28, 2018
• Last Updated: April 27, 2026
• Results First Posted: April 27, 2026

Record last verified: 2026-04

Locations

US (1)