Dataset Information

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 t_max of 1-2 h, and eliminated, with a t_1/2 of approximately 2 h. Both t_max and t_1/2 were independent of dose level, while C_max 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).

SUBMITTER: Pitchford LM

PROVIDER: S-EPMC6321651 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Pitchford Lisa M LM Rathmacher John A JA Fuller John C JC Daniels J Scott JS Morrison Ryan D RD Akers Wendall S WS Abumrad Naji N NN Amarnath Venkataraman V Currey Patricia M PM Roberts L Jackson LJ Oates John A JA Boutaud Olivier O

BMC pharmacology & toxicology 20190105 1

<h4>Background</h4>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.<h4>Methods</h4>In this fi ...[more]

PMID: 30611293

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Project description:BackgroundOlmesartan is an angiotensin II receptor antagonist and is effective and well tolerated in the treatment of arterial hypertension. Probenecid is a well-established hypouricemic agent for the treatment of hyperuricemia and gout.ObjectiveThe goal of this study was to examine the impact of coadministration of probenecid on the pharmacokinetic parameters and tolerability of olmesartan in healthy volunteers.MethodsIn a randomized, open-label, 2-way crossover study, 12 volunteers received 2 oral treatments (olmesartan alone or olmesartan plus probenecid) separated by 4 days. Blood samples were obtained for a 48-hour pharmacokinetic evaluation after drug administration. Tolerability was assessed by monitoring vital signs and laboratory tests before and after administration of the study drug.ResultsPharmacokinetic parameters were evaluated in 6 male and 6 female healthy volunteers (mean age, 22 [range, 20-25] years]; weight, 56.0 [range, 51.0-60.0] kg). Probenecid coadministration increased olmesartan Css-av, AUC0→∞, and AUC0-48 by 40%, 50%, and 50%, respectively (P = 0.018, 0.000, 0.000, respectively), but there was no statistical significance for Tmax, t1/2, Css-max, and Css-min between olmesartan plus probenecid and olmesartan alone (P = 0.697, 0.053, 0.521, and 0.734, respectively). No serious adverse event (AE) was reported during the study. The proportion of volunteers with AEs in the olmesartan plus probenecid period (5 of 12 [42%]) was higher than that in the olmesartan-alone period (1 of 12 [8%]). All of the AEs during the olmesartan plus probenecid period were abnormal routine urine test results. The AE in olmesartan-alone period was dizziness. All AEs were classified as mild and considered to be at least possibly related to treatment. All volunteers recovered from the AEs by 2 weeks after the end of the study.ConclusionsProbenecid increases the exposure speed of olmesartan by increasing the AUC0-48, AUC0→∞, and Css-av. The combined treatment of olmesartan medoxomil with probenecid may increase the occurrence of genitourinary side effects. ClinicalTrials.gov identifier: NCT01907373.

Dataset Information

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

Background

Methods

Results

Conclusions

Trial registration

Publications

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

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