Alcobra Ltd. announced via press release that it has begun a Phase III trial for Metadoxine Extended Release (MDX). The start of the clinical trial follows the Food and Drug Administration’s (FDA) approval of the company’s Investigational New Drug (IND) application. MDX has promise for cognitive disorders like attention deficit hyperactivity disorder (ADHD) and Fragile X Syndrome. The trial underway is for adults with ADHD. Dr. Yaron Daniely, President and Chief Executive Officer of Alcobra, said, "Building upon our two successful Phase II placebo-controlled studies, this Phase III study is designed to confirm MDX as a fast-acting, highly effective and well tolerated non-scheduled ADHD drug candidate. We expect the trial to be completed in the second half of 2014."
Attention Deficit Hyperactivity Disorder
ADHD is a cognitive disorder affecting children and adults. Symptoms include difficulty paying attention, hyperactivity, and impulsivity. Many children, up to 60%, move into adulthood with significant impairments. Treatment often includes stimulant drugs, which have common side effects like trouble falling asleep and rare side effects like personality changes and tics. Stimulants also carry the risks of abuse and addiction. Therefore, new drugs are needed for the condition that are safe, effective, and non-addictive.
Metadoxine has novel mechanism of action, different than other ADHD drugs. MDX does not work on serotonin, dopamine, and norepinephrine. Instead, it binds the 5-HT2B receptor, a member of the serotonin family. Blocking and antagonizing the 5-HT2B receptor may facilitate synaptic flexibility, thereby improving learning capacity and memory retention. This explanation is a hypothesis, supported by recent studies in electrophysiology. MDX reduced glutamatergic excitatory tones and increased GABAergic inhibitory transmissions. Additionally, in abuse studies, rats did not self-medicate with the drug, suggesting that humans are not likely to become addicted.
MDX Clinical Trial
Over 300 patients in Israel and the U.S. will receive either MDX or a placebo in a two-week time frame. Investigators are using the Conners' Adult ADHD Rating Scale (CAARS-INV) to assess changes in symptoms. The secondary endpoint uses the TOVA (Test of Variables of Attention), used in previous trials. Previous studies have shown that MDX is well tolerated, so investigators will be looking for more evidence that patients are comfortable with the drug and its delivery system.