News and Publications
A Phase 1 SAD and MAD trial of EVX-101, a novel gastro-retentive prolonged release 5-HTP/low-dose carbidopa tablet, in healthy subjects taking escitalopram.
Carpenter, D., McKenzie, L., Beaudoin, S., et al. A Phase 1 SAD and MAD trial of EVX-101, a novel gastro-retentive prolonged release 5-HTP/low-dose carbidopa tablet, in healthy subjects taking escitalopram. American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, May 30-June2, 2023.
This Phase 1 double-blind, placebo-controlled, single-ascending dose (SAD) and multiple-ascending dose (MAD) trial demonstrated that escalating doses of EVX-101 up-titrated every 7 days over 4 weeks appeared to be safe in healthy volunteers taking a first-line anti-depressant. No serious or severe adverse events were reported. Mild-moderate gastrointestinal-related AEs were most frequently reported, consistent with a serotonergic mechanism. Tolerability was improved by titration. At steady state, all administered dose levels achieved 5-HTP plasma levels at or above the targeted therapeutic level (≥100 ng/ml). Evidence of target engagement was also demonstrated, i.e., elevation of brain extracellular serotonin beyond the first-line antidepressant effect.
Slow-release delivery enhances the pharmacological properties of oral 5-hydroxytryptophan: mouse proof-of-concept
Jacobsen JPR, Oh A, Bangle R, et al. Slow-release delivery enhances the pharmacological properties of oral 5-hydroxytryptophan: mouse proof-of-concept. Neuropsychopharmacology. 2019;44(12):2082-2090.
This comprehensive study was designed to optimize translational fidelity, It reports that high-dose oral adjunctive 5-HTP slow-release in mice is safe and effective in amplifying brain serotonin neurotransmission beyond the SSRI effect, as assessed by behavioral, biochemical, and gene transcription measures.
Adjunctive 5-hydroxytryptophan slow-release for treatment-resistant depression: clinical and preclinical rationale
Jacobsen JPR, Krystal AD, Krishnan KRR, et al. Adjunctive 5-hydroxytryptophan slow-release for treatment-resistant depression: clinical and preclinical rationale. Trends Pharmacol Sci. 2016;37(11):933-944.
This paper reviews the multipronged clinical data supporting that adjunctive 5-HTP SR could treat depression patients responding inadequately to first-line SSRI/SNRI antidepressants. That clinical data relates to earlier 5-HTP clinical research as well as clinical research with serotonergic antidepressants and compounds more broadly. Key supportive preclinical data is reviewed as well.
SSRI augmentation by 5-hydroxytryptophan slow release: mouse pharmacodynamic proof of concept
Jacobsen JP, Rudder ML, Roberts W, et al. SSRI augmentation by 5-hydroxytryptophan slow release: mouse pharmacodynamic proof of concept. Neuropsychopharmacology. 2016;41(9):2324-2334.
This study reports that 5-HTP slow-release synergizes with chronic SSRI in elevating extracellular serotonin in mice. It further demonstrates, assessing across a variety of physiological and behavioral measures, that slow-release delivery dramatically improves the safety and tolerability of 5-HTP administration.