VistaGen Therapeutics has reported that AV-101 did not meet the primary endpoint in a Phase II clinical trial of patients with major depressive disorder (MDD).

AV-101 is an antagonist of N-methyl-D-aspartate (NMDA) receptor glycine site. It is formulated as an oral prodrug of 7-chlorokynurenic acid (7-Cl-KYNA) and is being developed to treat various central nervous system (CNS) disorders.

The double-blind, placebo-controlled, multi-centre, sequential parallel comparison design (SPCD) Phase II trial, named ELEVATE, assessed the safety, tolerability and efficacy of 1,440mg a day AV-101 as adjunctive therapy for MDD.

The study enrolled 199 patients who did not experience an adequate response to a stable standard antidepressant therapy dose at 25 sites in the US.

Eligible participants continued their stable dose of a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) during the trial.

The primary efficacy endpoint was the absolute change in the Montgomery-Åsberg Depression Rating Scale (MADRS-10) score of AV-101 from baseline to the end of the therapy period compared to placebo.

According to the data, ELEVATE failed to meet the primary goal, with no difference in the MADRS-10 total score between AV-101 and placebo groups.

Safety analysis showed that AV-101 was well-tolerated, without any psychotomimetic side effects or serious adverse events.

VistaGen Therapeutics CEO Shawn Singh said: “While we are disappointed with the top-line results of the study, it is possible that efficacy may have been compromised by either insufficient transport of AV-101 across the blood-brain barrier or subsequent inadequate concentrations of its active metabolite, 7-Cl-KYNA, in the brain.”

Singh added that the company will further analyse the Phase II data for AV-101’s effects on other endpoints and pharmacokinetics.

In addition to depression, the drug candidate is being studied for the treatment of epilepsy, neuropathic pain, levodopa-induced dyskinesia, and suicidal ideation.