Evecxia Therapeutics has reported positive results from a two-part single ascending dose (SAD) and multiple ascending dose (MAD) Phase I trial of EVX-101 in healthy volunteers treated with first-line antidepressant escitalopram.
The Phase I trial was carried out at Quotient Sciences’ Nottingham facility in the UK. The double-blind, placebo-controlled trial evaluated the safety, tolerability, pharmacokinetic, and pharmacodynamic data of the therapy.
Evecxia also announced the planned Phase II adjunctive EVX-101 trial design to treat major depressive disorder (MDD) patients who are not responding adequately to a first-line antidepressant.
The new, gastro-retentive, sustained-release tablet formulation of 5-hydroxytryptophan (5-HTP) EVX-101 is administered in addition to a first-line antidepressant.
It helps elevate extracellular serotonin beyond the first-line antidepressant effect.
As part of the study design, escitalopram was administered pre-randomisation and throughout the randomised treatment period in all participants to model first-line antidepressant therapy.
In Part 1 (SAD), two cohorts received EVX-101 over one day and in Part 2 (MAD), a single cohort of subjects was up-titrated weekly over 28 days.
In Part 2 MAD, 5-HTP plasma levels rose with each escalation in carbidopa dose and 5-HTP accumulated several-fold over days when EVX-101 was dosed to steady state.
For evaluating pharmacodynamics, an acute transient rise in serum cortisol was used as a validated neuroendocrine biomarker of acute elevation in brain extracellular serotonin.
With regard to safety and tolerability, no dose levels of EVX-101 were associated with significant changes in clinical labs, vital signs, or ECGs.
All adverse events reported were found to be mild or moderate, generally transient, and consistent with the serotonergic pharmacology and no serotonin toxicity or other safety signals were observed.
Evecxia president and CEO Joseph Patti said: “We are excited to advance our lead candidate for the adjunctive treatment of patients suffering from disabling symptoms of depression despite receiving antidepressant treatment.
“EVX-101 could serve a large outpatient population not helped by available treatment options.”