Ecopipam Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ecopipam Active substance being tested, orally once a day at bedtime |
Drug: Ecopipam
Antagonist of the dopamine D1 receptor
Other Names:
|
| Placebo Comparator: Placebo Inactive substance being tested, orally once a day at bedtime |
Drug: Placebo
Placebo for Ecopipam
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | H.J. Jinnah | Atlanta | Georgia | United States | 30322 |
| 2 | Hospital Universitario La Paz | Madrid | Spain |
Sponsors and Collaborators
- Psyadon Pharma
Investigators
- Principal Investigator: H J Jinnah, MD, Emory University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- PSY102
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Ecopipam Then Placebo Then Ecopipam | Placebo Then Ecopipam Then Placebo |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Period Title: Overall Study | ||
| STARTED | 5 | 4 |
| Completed Period 1 | 2 | 4 |
| Completed Period 2 | 2 | 1 |
| Completed Period 3 | 2 | 1 |
| COMPLETED | 1 | 2 |
| NOT COMPLETED | 4 | 2 |
Baseline Characteristics
| Arm/Group Title | Ecopipam Then Placebo Then Ecopipam | Placebo Then Ecopipam Then Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 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 | 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 | Total of all reporting groups |
| Overall Participants | 5 | 4 | 9 |
| Age (years) [Mean (Full Range) ] | |||
| Mean (Full Range) [years] |
10.8
|
9.8
|
10.3
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
5
100%
|
4
100%
|
9
100%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
2
40%
|
1
25%
|
3
33.3%
|
| Spain |
3
60%
|
3
75%
|
6
66.7%
|
| Weight (kg) [Mean (Full Range) ] | |||
| Mean (Full Range) [kg] |
28.3
|
21.9
|
25.4
|
| BMI (kg/m^2) [Mean (Full Range) ] | |||
| Mean (Full Range) [kg/m^2] |
15.6
|
13.8
|
14.8
|
Outcome Measures
| Title | Behavior Problems Inventory - Self-Injurious Behavior Subscale |
|---|---|
| Description | 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), |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who completed the BPI-Self Injurious Behavior survey for 3 or more time points |
| Arm/Group Title | Subject #1: Ecopipam Then Placebo Then Ecopipam | Subject #2: Ecopipam Then Placebo Then Ecopipam | Subject #3: Placebo Then Ecopipam Then Placebo | Subject #4: Placebo Then Ecopipam Then Placebo |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 |
| Measure Participants | 1 | 1 | 1 | 1 |
| BPI Self-Injurious Behavior Subscale, Baseline |
26
|
10
|
78
|
27
|
| BPI Self-Injurious Behavior Subscale, 6 weeks |
24.1
|
4.3
|
58.3
|
22.6
|
| BPI Self-Injurious Behavior Subscale, 12 weeks |
25.2
|
11.6
|
21.5
|
16.0
|
| BPI Self-Injurious Behavior Subscale, 18 weeks |
21
|
6.6
|
28.7
|
NA
|
| Title | Effect of Ecopipam Withdrawal and Maintenance |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 0 participants analyzed because data are not reliable |
| Arm/Group Title | Ecopipam | Placebo |
|---|---|---|
| Arm/Group Description | Active substance being tested, orally once a day at bedtime Ecopipam: Antagonist of the dopamine D1 receptor | Inactive substance being tested, orally once a day at bedtime Placebo: Placebo for Ecopipam |
| Measure Participants | 0 | 0 |
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose |
| Arm/Group Title | Ecopipam | Placebo |
|---|---|---|
| Arm/Group Description | Active substance being tested, orally once a day at bedtime for 6 weeks Ecopipam: Antagonist of the dopamine D1 receptor | Inactive substance being tested, orally once a day at bedtime for 6 weeks Placebo: Placebo for Ecopipam |
| Measure Participants | 9 | 6 |
| Non-Serious |
42
|
7
|
| Serious |
2
|
1
|
Adverse Events
| Time Frame | adverse events collected while participants were receiving ecopipam or placebo, either for 1 period (up to 6 weeks) or 2 periods (up to 12 weeks) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were collected for 3 double-blind periods | |||
| Arm/Group Title | Ecopipam | Placebo | ||
| Arm/Group Description | Active substance being tested, orally once a day at bedtime Ecopipam: Antagonist of the dopamine D1 receptor | Inactive substance being tested, orally once a day at bedtime Placebo: Placebo for Ecopipam | ||
All Cause Mortality |
||||
| Ecopipam | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Ecopipam | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/9 (22.2%) | 1/6 (16.7%) | ||
| Nervous system disorders | ||||
| Dystonic crisis | 1/9 (11.1%) | 0/6 (0%) | ||
| Psychiatric disorders | ||||
| Unusual somnolence | 1/9 (11.1%) | 0/6 (0%) | ||
| Renal and urinary disorders | ||||
| Nephrolithiasis | 0/9 (0%) | 1/6 (16.7%) | 1 | |
Other (Not Including Serious) Adverse Events |
||||
| Ecopipam | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/9 (88.9%) | 2/6 (33.3%) | ||
| Blood and lymphatic system disorders | ||||
| Eosinophilia | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 |
| Constipation | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 |
| Diarrhoea | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Dysphagia | 5/9 (55.6%) | 5 | 0/6 (0%) | 0 |
| Vomiting | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| General disorders | ||||
| Mucosal inflammation | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 |
| Pyrexia | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 |
| Infections and infestations | ||||
| Oral candidiasis | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Lip injury | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Investigations | ||||
| Body temperature increased | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Transaminases increased | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Nervous system disorders | ||||
| Dyskinesia | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 |
| Dystonia | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 |
| Opisthotonus | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 |
| Somnolence | 5/9 (55.6%) | 5 | 0/6 (0%) | 0 |
| Tremor | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Psychiatric disorders | ||||
| Agitation | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 |
| Anxiety | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 |
| Compulsive lip biting | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Depressed mood | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Depression | 3/9 (33.3%) | 3 | 0/6 (0%) | 0 |
| Insomnia | 2/9 (22.2%) | 2 | 1/6 (16.7%) | 1 |
| Self injurious behaviour | 4/9 (44.4%) | 4 | 1/6 (16.7%) | 1 |
| Renal and urinary disorders | ||||
| Nephrolithiasis | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchospasm | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 |
| Choking | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | President/CEO |
|---|---|
| Organization | Psyadon Pharmaceuticals |
| Phone | 301-919-2020 |
| info@psyadonrx.com |
- PSY102