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PHASE 1, DOSE-RANGING STUDY OF EMIXUSTAT HYDROCHLORIDE (ACU-4429), A NOVEL VISUAL CYCLE MODULATOR, IN HEALTHY VOLUNTEERS.
MedLine Citation:
PMID:  24056528     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 Tmax, 3.0-5 hours) and readily eliminated (mean t1/2, 4.6-7.9 hours), and mean Cmax and AUC0-24 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.
Authors:
Ryo Kubota; Suliman Al-Fayoumi; Suresh Mallikaarjun; Shiva Patil; Claes Bavik; John W Chandler
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-9-19
Journal Detail:
Title:  Retina (Philadelphia, Pa.)     Volume:  -     ISSN:  1539-2864     ISO Abbreviation:  Retina (Philadelphia, Pa.)     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-9-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309919     Medline TA:  Retina     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*Acucela Inc, Seattle, Washington; and †Otsuka Pharmaceutical Development and Commercialization, Inc (OPDC), Princeton, New Jersey.
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