A phase 1 randomized, placebo-controlled study to investigate potential interactions between ASP8062, a positive allosteric modulator of the GABAB receptor, and morphine in recreational opioid users

Abstract

Background: Recent increases in opioid use and subsequent opioid use disorder are a major public health crisis in the United States. Aims: This phase 1 randomized, placebo-controlled study investigated the safety, tolerability, and pharmacokinetics (PKs) of ASP8062, a γ-aminobutyric acid B receptor-positive allosteric modulator, with and without administration of morphine in participants who used opioids recreationally. Methods: Participants were randomly assigned (2:1) to daily dosing with ASP8062 25 mg or placebo on days 1–10. On day 10, all participants received morphine as a single oral dose of 45 mg; assessments were performed on days 11–16. The primary end point was safety, evaluated as the nature, frequency, and severity of adverse events, and end-tidal CO2 levels. PK end points were a secondary outcome measure. Results: A total of 24 participants (aged 21–54 years) received ASP8062 ( n = 16) or placebo ( n = 8). There were no deaths or serious adverse events leading to treatment discontinuation during the study. Most adverse events were mild, with numerically lower absolute number of adverse events reported with ASP8062 plus morphine versus placebo plus morphine. ASP8062 plus morphine did not increase respiratory depression, potential drug abuse- or withdrawal-related adverse events. There were no significant PK interactions. Conclusions: In this phase 1 study, we did not observe any unexpected safety signals or notable PK interactions with concomitant morphine administration. These data suggest a potentially low risk for an increase in drug abuse- or withdrawal-related adverse events or respiratory distress in participants exposed to ASP8062 and morphine.