NCT00140179

Valnoctamide as a Valproate Substitute With Low Teratogenic Potential: Double-Blind Controlled Clinical Trial

Completed Phase 3 Last updated 23 November 2009

What this trial tests

Phase 3 trial testing valnoctamide in Mania in 80 participants. Completed in 1 May 2008.

Timeline

1 September 2004

1 May 2008

Quick facts

Lead sponsor	Beersheva Mental Health Center
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	80
Start date	1 September 2004
Estimated completion	1 May 2008
Sites	3 locations across Israel

Drugs / interventions tested

• valnoctamide (VALNOCTAMIDE) — full drug profile →

Conditions studied

• Mania — all drugs for Mania →
• Schizoaffective Disorder, Manic Type — all drugs for Schizoaffective Disorder, Manic Type →

Sponsor

Beersheva Mental Health Center — full company profile →

Who can join

Adults 18 to 60, any sex, with Mania or Schizoaffective Disorder, Manic Type. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Brief Psychiatric Rating Scale
• Young Mania Rating Scale
• Clinical Global Impression

Sponsor's own description

Valproic acid is a leading mood stabilizer for the treatment of bipolar disorder. Its well-known teratogenicity limits its use in young women of childbearing age. According to toxicologic studies the teratogenicity of valproate stems from its free carboxylic group. Valnoctamide is an isomer and an analog of valpromide. Unlike valpromide, valnoctamide does not undergo a biotransformation to the corresponding free acid. It is also likely or at least possible that valnoctamide is anti-bipolar. In mice valnoctamide has been shown to be distinctly less teratogenic than valproate. An injection at day 8 of gestation produced only 1% exencephaly (as compared to 0-1% in control mice and 53% in valproate treated mice).

The investigators are performing a double-blind controlled trial of valnoctamide as an anti-bipolar drug. If shown to be anti-bipolar, valnoctamide could be an important valproate substitute for young women with bipolar disorder who are at risk of pregnancy. Patients newly admitted to the Beersheva Mental Health Center may participate if they meet Diagnostic and Statistical Manual of Mental Disorders - 4th edition (DSM-IV) criteria for mania or schizoaffective disorder, manic type. Patients admitted to the study are treated with risperidone at doses of the physicians' discretion beginning with 2 mg daily on days 1 and 2. Valnoctamide or placebo is begun at doses of 600 mg per day (200 mg three times daily) and increased to 1200 mg (400 mg three times daily) after four days.

Weekly ratings by a psychiatrist blind to the study drug are conducted using the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMS), and the Clinical Global Impression (CGI). Weekly blood is drawn for drug levels of valnoctamide to be measured by gas chromatography. Each patient receives valnoctamide or placebo for 5 weeks.

Low teratogenic mood stabilizers are a high priority for current research.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Valproic Acid: second generation.
   Bialer M, Yagen B. · · 2007 · cited 96× · PMID 17199028 · DOI 10.1016/j.nurt.2006.11.007