Tolerability, Pharmacokinetics, and Neuroendocrine Effects of PRX‐00023, a Novel 5‐HT1A Agonist, in Healthy Subjects

Abstract

PRX-00023 is a novel, nonazapirone 5-HT1A agonist in clinical development for treatment of affective disorders. The objectives of the initial clinical phase I studies (a single ascending dose study and multiple dose-ascending and high-dose titration studies) were to measure the pharmacokinetics, pharmacodynamic (neuroendocrine) effects, and tolerability of PRX-00023 in healthy subjects. The studies evaluated 10-mg to 150-mg doses of PRX-00023 in up to 112 healthy male and female subjects aged 18 to 54 years. Single and multiple oral doses of PRX-00023 were found to be safe and well tolerated in healthy subjects. PRX-00023 was absorbed relatively rapidly, with a tmax of 0.5 to 2 hours, and eliminated with a half-life of approximately 12 hours. PRX-00023 treatment transiently increased blood prolactin levels 2 to 3 hours after administration, consistent with its mechanism as a 5-HT1A agonist.

A Novel Study Using Accelerated Mass Spectrometry to Evaluate the Pharmacokinetics of Total 14C AL‐8309 (Tandospirone) Following Topical Ocular Administration in Healthy Male Subjects

“…In this study, AL‐8309 was safe and well tolerated in these healthy adult male subjects. There were no serious adverse events related to the radioactive dose, and all treatment‐associated events (lightheadedness and dizziness) were mild in intensity and related more to the 5HT1A agonism effects 11 . This is the first reported use of AMS technology with a topically applied ophthalmic product.…”

“…There were no serious adverse events related to the radioactive dose, and all treatment-associated events (lightheadedness and dizziness) were mild in intensity and related more to the 5HT1A agonism effects. 11 This is the first reported use of AMS technology with a topically applied ophthalmic product. The results from the present study guided the team to continue monitoring metabolites observed to be greater than 10% of the parent drug exposure in the future AL-8309 clinical trials.…”