Pharmacological profile of ALKS 7119, an investigational compound evaluated for the treatment of neuropsychiatric disorders, in healthy volunteers. Issue 6 (31st January 2022) - Dijkstra, Francis M.
Abstract : Aims: ALKS 7119 is a novel compound with in vitro affinity highest for the SERT, and for μ receptor, α1A ‐adrenoceptor, α1B ‐adrenoceptor, NMDA receptor and sigma non‐opioid intracellular receptor 1. This first‐in‐human study evaluated safety and PK/PD effects of single ascending doses (SAD) of ALKS 7119 in healthy males and compared effects with neurotransmitter modulators with partially overlapping targets. Methods: In 10 cohorts ( n = 10 subjects each), PK, safety and PD (NeuroCart tests, measuring neurophysiologic effects [pupillometry, pharmaco‐EEG (pEEG)], visuomotor coordination, alertness, [sustained] attention [saccadic peak velocity, adaptive tracking], subjective drug effects [VAS Bowdle and VAS Bond and Lader] and postural stability [body sway]) were evaluated. Neuroendocrine effects (cortisol, prolactin, growth hormone) were measured. Data were analysed over the 12‐hour post‐dose period using mixed‐effects model for repeated measure (MMRM) with baseline as covariate. Results: ALKS 7119 demonstrated linear PK and was generally well tolerated. QTcF interval increases of 30–60 ms compared to baseline were observed with ALKS 7119 doses of ≥50 mg without related adverse events. Significant increases in left and right pupil/iris ratio were observed at dose levels ≥50 mg (estimate of difference [95% CI], P ‐value) (0.04 [0.01; 0.07], P < .01) and (0.06 [0.03; 0.09], P = .01), respectively. From dose levels ≥50 mg significant increases (% change) of serum cortisol (51.7 [8.4; 112.3], P = .02) and prolactin (77.9 [34.2; 135.8], P < .01) were observed. Conclusion: In line with ALKS 7119's in vitro pharmacological profile, the clinical profile observed in this study is most comparable to SERT inhibition.