Safety and Tolerability of the D1 Dopamine Receptor Antagonist Ecopipam in Patients With Lesch-Nyhan Disease

• Sponsor: Psyadon Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01065558
• Collaborator: (none)
• Enrollment: 5
• Locations: 2
• Arm: 1
• Duration (Months): 15.9
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effects of ecopipam in patients with Lesch-Nyhan Disease (LND). Ecopipam specifically blocks the actions of one chemical in the brain that helps nerves talk to one another; ecopipam does this by stopping the chemical (dopamine) from binding to one of its family of receptors (i.e, the D1 family). LND is a very rare genetic disease. The sponsor is doing this study to find out what side effects ecopipam causes in LND patients, and whether ecopipam may be able to relieve the self-injurious behaviors seen in these patients.

Condition or Disease	Intervention/Treatment	Phase
Lesch-Nyhan Disease	Drug: Ecopipam	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Safety and Pilot Activity Study of Ecopipam (PSYRX 101) in the Symptomatic Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ecopipam 12.5 - 200 mg/day Patients were administered ecopipam on an escalated dosing schedule over 11 days starting at 12.5 mg/day and increasing to the maximal tolerated dose or to 200 mg/day.	Drug: Ecopipam; Tablets, once daily, for two weeks up to 200 mg/day; Other Names: PSYRX101, SCH 39166

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinically Significant Changes in Standard Laboratory Tests [Two weeks]

   This study's primary outcome is the safety of ecopipam in Lesch-Nyhan patients as measured by standard clinical laboratory tests. The patients will also be observed and questioned about other side effects, such as whether they feel more or less tired.Standard clinical laboratory tests for liver, kidney and blood function were conducted. The normal ranges for each of these tests were different and are too numerous to be individually listed here. However, if any individual value were to be either three-times greater or lesser than the upper or the lower limit of the test, then that value was considered to have been changed.

Secondary Outcome Measures

1. Decrease in Self-injurious Behavior at End of Study (Two Weeks After Screening) Compared to Screening [Screening visit and end of study (two weeks)]

   Change in the self-injurious subscale of the Behavior Problems Inventory (BPI). the BPI is a well-validate test to evaluate the frequency and severity of a patient's self-injurious behavior. Values range from 0 to 50, and a low score means few/less severe behaviors

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Diagnosis of Lesch-Nyhan disease with moderate to severe Self- Injurious Behavior and are routinely restrained

• Male - 6 years of age and above

• Body weight greater than or equal to 44 pounds

Exclusion Criteria:

• Taking Neuroleptic or Dopamine Depleting medications

• Currently treated with medications for depression or seizures

• Impaired renal function

• Medical conditions that may interfere with completing the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at San Diego	San Diego	California	United States	92103
2	Emory Univesity	Atlanta	Georgia	United States	30329

Sponsors and Collaborators

• Psyadon Pharma

Investigators

• Principal Investigator: Hyder A Jinnah, MD, Emory University
• Principal Investigator: William L Nyhan, MD, University of California, San Diego

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chipkin RE, Iorio LC, Coffin VL, McQuade RD, Berger JG, Barnett A. Pharmacological profile of SCH39166: a dopamine D1 selective benzonaphthazepine with potential antipsychotic activity. J Pharmacol Exp Ther. 1988 Dec;247(3):1093-102.

• Responsible Party: Psyadon Pharma
• ClinicalTrials.gov Identifier: NCT01065558
• Other Study ID Numbers: Ecopipam and Lesch-Nyhan
• First Posted: Feb 9, 2010
• Last Update Posted: Apr 18, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by Psyadon Pharma: Ecopipam; Lesch-Nyhan Disease; Safety; Self-Injurious Behavior
• Additional relevant MeSH terms: Lesch-Nyhan Syndrome; Self-Injurious Behavior; Ecopipam

Study Results

Participant Flow

Recruitment Details	Patients were recruited by the investigators according to the inclusion and exclusion criteria
Pre-assignment Detail	No preassignment

Arm/Group Title	Ecopipam (12.5- 200 mg/Day)
Arm/Group Description	Patients were given ecopipapm over an 11 day period as follows: day 1 12.5 mg/day day 2-3 25 mg/day day 4-5 50 mg/day day 6-9 100 mg/day day 9-11 200 mg/day Note: Doses were reduced as necessary to a previously tolerated dose if paitents reached doses that were not safely tolerable.
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ecopipam
Arm/Group Description
Overall Participants	5
Age (Count of Participants)
<=18 years	4 80%
Between 18 and 65 years	1 20%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.4 (17.9)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	5 100%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Standard Laboratory Tests
Description	This study's primary outcome is the safety of ecopipam in Lesch-Nyhan patients as measured by standard clinical laboratory tests. The patients will also be observed and questioned about other side effects, such as whether they feel more or less tired.Standard clinical laboratory tests for liver, kidney and blood function were conducted. The normal ranges for each of these tests were different and are too numerous to be individually listed here. However, if any individual value were to be either three-times greater or lesser than the upper or the lower limit of the test, then that value was considered to have been changed.
Time Frame	Two weeks

Outcome Measure Data

Analysis Population Description

All patients were analyzed

Arm/Group Title	Ecopipam Treated Patients
Arm/Group Description	These were patients who had diagnoses Lesch-Nyhan Disease based either on their genetic changes or on changes of specific enzymes in their blood.
Measure Participants	5
Number [Participants]	0 0%

2. Secondary Outcome

Title	Decrease in Self-injurious Behavior at End of Study (Two Weeks After Screening) Compared to Screening
Description	Change in the self-injurious subscale of the Behavior Problems Inventory (BPI). the BPI is a well-validate test to evaluate the frequency and severity of a patient's self-injurious behavior. Values range from 0 to 50, and a low score means few/less severe behaviors
Time Frame	Screening visit and end of study (two weeks)

Outcome Measure Data

Analysis Population Description

All patients who received any dose of ecopipam were in the analysis population

Arm/Group Title	Ecopipam Treated Patients
Arm/Group Description	These were patients who had diagnoses Lesch-Nyhan Disease based either on their genetic changes or on changes of specific enzymes in their blood.
Measure Participants	5
Mean (Standard Deviation) [Change in BPI score]	22.5 (13.4)

Adverse Events

Time Frame	12 days of active treatment and 28 days follow-up
Arm/Group Title	Ecopipam Treated Patients
Arm/Group Description
All Cause Mortality
	Ecopipam Treated Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ecopipam Treated Patients
	Affected / at Risk (%)	# Events
Total	2/5 (40%)
Infections and infestations
Respiratory Infection	1/5 (20%)	1
Renal and urinary disorders
Flank Pain	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Ecopipam Treated Patients
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Gastrointestinal disorders
Nausea	2/5 (40%)	2
Nervous system disorders
Sedation	3/5 (60%)	3
Dystonia	2/5 (40%)	2

Limitations/Caveats

This was an open label trial of oral ecopipam in pediatric, adolescent and adult patients with Lesch-Nyhan Disease.In this population, ecopipam's safety and PK was similar to non-LND subjects.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.