Lesch-Nyhan Disease, Self-injurious Behavior
Conditions
Keywords
Lesch Nyhan Disease, Self-Injury
Brief summary
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
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.
Interventions
DRUGEcopipam
Antagonist of the dopamine D1 receptor
DRUGPlacebo
Placebo for Ecopipam
Sponsors
Psyadon Pharma
Emalex Biosciences Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Behavior Problems Inventory - Self-Injurious Behavior Subscale | Baseline, end of period 1 (6 weeks), end of period 2 (12 weeks), end of period 3 (18 weeks), | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Ecopipam Withdrawal and Maintenance | Baseline, 6 weeks, 12 weeks, 18 weeks | 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 |
| 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 | Total duration over which participants recieved double-blind ecopipam or placebo, up to 6 or 12 weeks | 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 |
Countries
Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ecopipam Then Placebo Then Ecopipam Ecopipam, the active substance being tested, 100mg tablets for body weight \> 20kg OR 50 mg tablets for body weight up to 20kg, once daily at bedtime for 6 weeks; then Placebo, the inactive substance being tested to be taken once a day at bedtime for 6 weeks; then Ecopipam, the active substance being tested, 100mg tablets for body weight \> 20kg OR 50 mg tablets for body weight up to 20kg, once daily at bedtime for 6 weeks | 5 |
| Placebo Then Ecopipam Then Placebo Placebo, the inactive substance being tested to be taken once a day at bedtime for 6 weeks; then Ecopipam, the active substance being tested, 100mg tablets for body weight \> 20kg OR 50 mg tablets for body weight up to 20kg, once daily at bedtime for 6 weeks; then Placebo, the inactive substance being tested to be taken once a day at bedtime for 6 weeks | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
Baseline characteristics
| Characteristic | Ecopipam Then Placebo Then Ecopipam | Placebo Then Ecopipam Then Placebo | Total |
|---|---|---|---|
| Age, Continuous | 10.8 years | 9.8 years | 10.3 years |
| BMI | 15.6 kg/m^2 | 13.8 kg/m^2 | 14.8 kg/m^2 |
| Region of Enrollment Spain | 3 participants | 3 participants | 6 participants |
| Region of Enrollment United States | 2 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
| Weight | 28.3 kg | 21.9 kg | 25.4 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 9 | 2 / 6 |
| serious Total, serious adverse events | 2 / 9 | 1 / 6 |
Outcome results
Primary
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.
Time frame: Baseline, end of period 1 (6 weeks), end of period 2 (12 weeks), end of period 3 (18 weeks),
Population: All participants who completed the BPI-Self Injurious Behavior survey for 3 or more time points
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Subject #1: Ecopipam Then Placebo Then Ecopipam | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, Baseline | 26 scores on a scale |
| Subject #1: Ecopipam Then Placebo Then Ecopipam | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 6 weeks | 24.1 scores on a scale |
| Subject #1: Ecopipam Then Placebo Then Ecopipam | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 12 weeks | 25.2 scores on a scale |
| Subject #1: Ecopipam Then Placebo Then Ecopipam | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 18 weeks | 21 scores on a scale |
| Subject #2: Ecopipam Then Placebo Then Ecopipam | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 6 weeks | 4.3 scores on a scale |
| Subject #2: Ecopipam Then Placebo Then Ecopipam | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 12 weeks | 11.6 scores on a scale |
| Subject #2: Ecopipam Then Placebo Then Ecopipam | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 18 weeks | 6.6 scores on a scale |
| Subject #2: Ecopipam Then Placebo Then Ecopipam | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, Baseline | 10 scores on a scale |
| Subject #3: Placebo Then Ecopipam Then Placebo | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 12 weeks | 21.5 scores on a scale |
| Subject #3: Placebo Then Ecopipam Then Placebo | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 6 weeks | 58.3 scores on a scale |
| Subject #3: Placebo Then Ecopipam Then Placebo | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 18 weeks | 28.7 scores on a scale |
| Subject #3: Placebo Then Ecopipam Then Placebo | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, Baseline | 78 scores on a scale |
| Subject #4: Placebo Then Ecopipam Then Placebo | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 18 weeks | NA scores on a scale |
| Subject #4: Placebo Then Ecopipam Then Placebo | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 6 weeks | 22.6 scores on a scale |
| Subject #4: Placebo Then Ecopipam Then Placebo | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, Baseline | 27 scores on a scale |
| Subject #4: Placebo Then Ecopipam Then Placebo | Behavior Problems Inventory - Self-Injurious Behavior Subscale | BPI Self-Injurious Behavior Subscale, 12 weeks | 16.0 scores on a scale |
Secondary
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
Time frame: Baseline, 6 weeks, 12 weeks, 18 weeks
Population: 0 participants analyzed because data are not reliable
Secondary
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
Time frame: Total duration over which participants recieved double-blind ecopipam or placebo, up to 6 or 12 weeks
Population: All participants who received at least one dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subject #1: Ecopipam Then Placebo Then Ecopipam | 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 | Non-Serious | 42 adverse events |
| Subject #1: Ecopipam Then Placebo Then Ecopipam | 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 | Serious | 2 adverse events |
| Subject #2: Ecopipam Then Placebo Then Ecopipam | 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 | Non-Serious | 7 adverse events |
| Subject #2: Ecopipam Then Placebo Then Ecopipam | 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 | Serious | 1 adverse events |