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

A Safety and Pilot Activity Study of Ecopipam (PSYRX 101) in the Symptomatic Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease

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.

Study Overview

• Status: Completed
• Conditions: Lesch-Nyhan Disease
• Intervention / Treatment: Drug: Ecopipam

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • University of California at San Diego
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory Univesity

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 63 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Significant Changes in Standard Laboratory Tests	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.	Two weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in Self-injurious Behavior at End of Study (Two Weeks After Screening) Compared to Screening	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	Screening visit and end of study (two weeks)

Collaborators and Investigators

• Sponsor: Psyadon Pharma
• Investigators: Principal Investigator: Hyder A Jinnah, MD, Emory University; Principal Investigator: William L Nyhan, MD, University of California, San Diego

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: February 6, 2010
• First Submitted That Met QC Criteria: February 8, 2010
• First Posted (Estimate): February 9, 2010

Study Record Updates

• Last Update Posted (Estimate): April 18, 2013
• Last Update Submitted That Met QC Criteria: April 17, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Safety; Self-Injurious Behavior; Ecopipam; Lesch-Nyhan Disease
• Additional Relevant MeSH Terms: Behavioral Symptoms; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Purine-Pyrimidine Metabolism, Inborn Errors; Self-Injurious Behavior; Lesch-Nyhan Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Ecopipam
• Other Study ID Numbers: Ecopipam and Lesch-Nyhan