First-in-human study assessing safety, tolerability, and pharmacokinetics of 2-hydroxybenzylamine acetate, a selective dicarbonyl electrophile scavenger, in healthy volunteers

Abstract

Background: 2-Hydroxybenzylamine (2-HOBA) is a selective scavenger of dicarbonyl electrophiles that protects proteins and lipids from being modified by these electrophiles. It is currently being developed for use as a nutritional supplement to help maintain good health and protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline associated with Mild Cognitive Impairment and Alzheimer's disease.

Methods: In this first-in-human study, the safety, tolerability, and pharmacokinetics of six ascending single oral doses of 2-HOBA acetate were tested in eighteen healthy human volunteers.

Results: Reported adverse events were mild and considered unlikely to be related to 2-HOBA. There were no clinically significant changes in vital signs, ECG recordings, or clinical laboratory parameters. 2-HOBA was fairly rapidly absorbed, with a tmax of 1-2 h, and eliminated, with a t1/2 of approximately 2 h. Both tmax and t1/2 were independent of dose level, while Cmax and AUC increased proportionally with dose level.

Conclusions: 2-HOBA acetate was safe and well-tolerated at doses up to 825 mg in healthy human volunteers, positioning it as a good candidate for continued development as a nutritional supplement.

Trial registration: This study is registered at ClinicalTrials.gov (NCT03176940).

Keywords: Humans; Pharmacokinetics; Safety; Salicylamine; γ-Ketoaldehydes.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the Vanderbilt University Institutional Review Board. All participants provided written informed consent before participating in the study.

Consent for publication

Not applicable.

Competing interests

JCF, LMP, and JAR are employed by and NNA is co-founder and part owner of Metabolic Technologies, Inc., which has executed an agreement for the rights to license the intellectual property for 2-hydroxybenzylamine from Vanderbilt University. JSD and RDM are employed by Sano Informed Prescribing, which received payment for services provided for this study. WSA received payment for the clinical pharmacokinetic analysis.

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Figures

Fig. 1

2-Hydroxybenzylamine (2-HOBA) plasma concentrations after oral administration of 2-HOBA acetate. 2-HOBA plasma concentration was measured for 24 h after oral administration of six ascending single doses of 2-HOBA acetate in healthy subjects (n=3 per dose level). Blood samples for pharmacokinetic analyses were collected at baseline, 0.5, 1, 2, 4, 8, and 24 h after 2-HOBA acetate administration for all dose levels. A 0.25-hour sample was only collected for dosages ≤ 200 mg, and a 6-h sample was only collected for dosages ≥ 330 mg. No 2-HOBA was detectable prior to administration (time 0) or at 24 h post-administration (assay limit of detection = 5 ng/mL)