Ecopipam Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease

Study Overview
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Brief Summary
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The purpose of this research study is to gather scientific information about the effectiveness and safety of the study drug, Ecopipam (PSYRX 101), for the treatment of self-injurious behaviors when compared with the effectiveness and safety of placebo (inactive substance) in subjects with Lesch-Nyhan Disease.

Detailed Description
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This study will be done in approximately 6 centers in approximately 4 countries, and approximately 24 subjects will be included. This study is divided into two parts. The first is a double-blinded portion lasting up to 18 weeks in total. The second portion is an optional open-label extension and lasts up to 54 weeks total. The total duration of the study, if you choose to participate in both portions, is anticipated to be up to approximately 78 weeks. The first portion of this study is double-blind and assignment to a treatment group is done randomly. In this study, there are two treatment groups. One group will receive Ecopipam for one 6-week period and placebo for two 6-week periods, and the other group will receive Ecopipam for two 6-week periods and placebo for one 6-week period. Subjects who did not experience any clinically significant side effects during the blinded portion of the study may be eligible to participate in an open-label extension that may last up to 54 weeks.

Official Title
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An Outpatient Phase 3 Efficacy Study of Ecopipam (PSYRX 101) in the Symptomatic Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease

Conditions
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Lesch-Nyhan Disease, Self-injurious Behavior

Intervention / Treatment
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* Drug: Ecopipam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have classic LND as defined by (a) characteristic clinical syndrome (evidence of overproduction of uric acid, severe generalized dystonia, frequent and persistent self-injurious behavior (SIB), and cognitive impairment) and (b) laboratory confirmation for mutation of the HPRT gene or severe deficiency of the associated enzyme. Subjects must have a minimum combined score of 20 on the Behavior Problems Inventory (BPI) SIB subscales for frequency and severity as assessed by the caregiver. Subjects must have a minimum score of 4 on the Physician's Global Impression (PGI) severity scale. Subject must be ≥ 6 years old. Subjects must weigh > 10 kg. Exclusion Criteria: Subjects who are currently treated with medications for seizures. Subjects who are on neuroleptics or dopamine-depleting agents. Subjects with impaired renal function as defined by a serum creatinine >1.5 mg/dL.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ecopipam<br>Active substance being tested, orally once a day at bedtime | Drug: Ecopipam<br>* Antagonist of the dopamine D1 receptor<br>* Other names: SCH 39166;|
| Placebo Comparator: Placebo<br>Inactive substance being tested, orally once a day at bedtime | Drug: Placebo<br>* Placebo for Ecopipam<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavior Problems Inventory - Self-Injurious Behavior Subscale | The primary endpoint is the BPI (SIB subscales - total for frequency and severity) as assessed by the caregiver. BPI Self-Injurious Behavior Subscale ranges from 0 to 45, with higher scores indicating more self-injurious behavior. | Baseline, end of period 1 (6 weeks), end of period 2 (12 weeks), end of period 3 (18 weeks), | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Ecopipam Withdrawal and Maintenance | The secondary objectives of this study are to assess the effect of withdrawal and maintenance of ecopipam's effects in subjects with LND. Measured by the number of participants whose score changes significantly from baseline on ecopipam or placebo | Baseline, 6 weeks, 12 weeks, 18 weeks | 
| Safety Summary of Ecopipam in Patients With Lesch-Nyhan Disease: Total Number of Serious and Non-Serious Adverse Events Experienced During 3 Double-blind Crossover Periods | An additional objective of the study is to assess the safety of ecopipam in subjects with LND for up to 52 weeks. Total number of serious and non-serious adverse events experienced by participants while receiving ecopipam or placebo. For additional detail, see Adverse Events | Total duration over which participants recieved double-blind ecopipam or placebo, up to 6 or 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lesch Nyhan Disease, Self-Injury