Metyrosine (Demser®) for the Treatment of Psychotic Disorders in Patients With Velocardiofacial Syndrome

A Double-Blind, Placebo-Controlled, Multi-Center, Randomized Trial of the Safety and Efficacy of Metyrosine (Demser®) for the Treatment of Psychotic Disorders in Patients With Velo-Cardio-Facial Syndrome

This is an exploratory clinical investigation. The objectives of this study are to evaluate the safety, steady-state pharmacokinetics, and efficacy of metyrosine (Demser®) for the treatment of psychosis in patients with velocardiofacial syndrome (VCFS).

Study Overview

• Status: Terminated
• Conditions: Psychosis; Velo-cardio-facial Syndrome
• Intervention / Treatment: Drug: Metyrosine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Syracuse, New York, United States, 13210
      • VCFS International Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Females of childbearing potential cannot be at risk of pregnancy during the study.
2. Genetically confirmed diagnosis of VCFS at the time of screening.
3. Must have one of the following Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV TR) diagnoses (applicable based upon clinical assessments): schizophrenia, schizoaffective disorder, psychosis not otherwise specified (NOS), bipolar disorder, or mood disorder with psychotic features.
4. A total PANSS composite score >65.
5. Willing to discontinue psychotropic medications. -

Key Exclusion Criteria:

1. Evidence of acute suicidality.
2. Known or observed clinically significant cardiovascular, pulmonary, renal, hepatic, or gastrointestinal disorders; other clinically significant psychiatric/neurological and sleep disorders by DSM-IV-TR criteria; endocrine, or hematological or metabolic diseases.
3. Full scale IQ of less than 50.
4. Pregnancy.
5. Not using a reliable means of contraception.
6. Systolic blood pressure of ≤110 mm/Hg or ≥160 mm/Hg, diastolic blood pressure ≤60 mm/Hg or ≥90 mm/Hg, or has clinically symptomatic orthostatic changes.
7. QTcF > 450 msec, or PR > 250 msec, or QRS > 110 msec on ECG.
8. History of seizure disorder. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo capsules were identically matched to Metyrosine.
Experimental: Metyrosine	Drug: Metyrosine; Metyrosine (250 mg capsules) were to be used at all dose levels (administered as multiples of that dosing unit). The starting dose was 250 mg/day of metyrosine. Dose escalation was to be carried out weekly for 8 weeks (up to a maximum of 8 capsules/day [2000 mg/day if metyrosine]) with dosage increments of 1 capsule/day per week. Weekly dose escalation was to stop based upon the investigator's assessment of safety, but not efficacy (i.e., dose escalation was to be forced to the maximum of 8 capsules/day assuming acceptable safety and tolerability).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To Evaluate the Safety of Metyrosine (Demser®) for the Treatment of Psychosis in Patients With VCFS	13 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To Evaluate the Efficacy of Metyrosine (Demser®) for the Treatment of Psychosis in Patients With VCFS	13 weeks

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: May 19, 2010
• First Submitted That Met QC Criteria: May 20, 2010
• First Posted (Estimate): May 21, 2010

Study Record Updates

• Last Update Posted (Actual): November 22, 2019
• Last Update Submitted That Met QC Criteria: November 12, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Patients with velocardiofacial syndrome and psychosis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Lymphatic Diseases; Endocrine System Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Parathyroid Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Chromosome Disorders; 22q11 Deletion Syndrome; Lymphatic Abnormalities; Hypoparathyroidism; Syndrome; Psychotic Disorders; Mental Disorders; DiGeorge Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; alpha-Methyltyrosine
• Other Study ID Numbers: 09-MET-101