Phase 1, dose-ranging study of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in healthy volunteers

Retina. 2014 Mar;34(3):603-9. doi: 10.1097/01.iae.0000434565.80060.f8.


Background: Emixustat hydrochloride (formerly ACU-4429) is a nonretinoid compound with a unique mode of action in the retinal pigment epithelium, where it modulates the biosynthesis of visual chromophore through its effect on retinal pigment epithelium-specific 65 kDa protein isomerase. This study provides clinicians with a background for understanding the pharmacokinetics and safety profile of orally administered emixustat.

Methods: This randomized, double-masked, placebo-controlled Phase 1b study evaluated the pharmacokinetics, tolerability, and safety of a 14-day course of oral emixustat (5, 10, 20, 30, or 40 mg) or placebo (3:1 ratio) once daily in healthy volunteers.

Results: A total of 40 subjects were enrolled (mean age, 38 years; 75% male). Emixustat (n = 30) was rapidly absorbed (median T(max), 3.0-5 hours) and readily eliminated (mean t(1/2), 4.6-7.9 hours), and mean C(max) and AUC(0-24) generally increased in proportion to dose. No significant accumulation of emixustat was observed with multiple-dose administration. Ocular adverse events occurred in 67% of the subjects who received emixustat; all were considered mild and resolved after study completion. Systemic adverse events were minimal.

Conclusion: Oral emixustat was safe and well tolerated when administered once daily for 14 days with minimal systemic adverse events reported. These data support evaluation of emixustat in subjects with geographic atrophy associated with dry age-related macular degeneration.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacokinetics*
  • Female
  • Geographic Atrophy / drug therapy
  • Humans
  • Male
  • Middle Aged
  • Phenyl Ethers / adverse effects
  • Phenyl Ethers / pharmacokinetics*
  • Propanolamines / adverse effects
  • Propanolamines / pharmacokinetics*


  • Enzyme Inhibitors
  • Phenyl Ethers
  • Propanolamines
  • emixustat