Study to Evaluate Effects of Emixustat Hydrochloride in Subjects With Proliferative Diabetic Retinopathy

Phase 2

Completed

Brief Summary: To evaluate the effects of oral emixustat hydrochloride (emixustat) on aqueous humor biomarkers associated with proliferative diabetic retinopathy (PDR) from baseline to week 12.

Detailed Description: This is a multicenter, randomized, double-masked, placebo-controlled study to evaluate the effects of emixustat in subjects with PDR. Subjects will be randomly assigned to either emixustat or placebo arms and treated once daily (QD) for 12 weeks. Doses of emixustat will be doubled on a weekly basis until week 4 after which all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen. Subjects in the placebo group will be mock-titrated on the same schedule as those in the emixustat arm.

Recruitment & Eligibility

Inclusion Criteria

Able and willing to provide written informed consent
Documented diagnosis of type 1 or type 2 diabetes mellitus
Meets specific ocular criteria for the study eye including but not limited to, the presence of PDR with or without diabetic macular edema in study eye for which treatment can be deferred for at least 4 weeks after Day 1 visit
Media clarity, pupillary dilation, and subject cooperation sufficient to obtain adequate assessments

Exclusion Criteria

Any condition that would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease or glycemic control)
History of myocardial infarction or other acute cardiac event
History of chronic renal failure requiring dialysis or kidney transplant
Prior participation in any clinical study of emixustat
Treatment with any investigational study drug within 30 days of screening
Known allergy to fluorescein sodium for injection in angiography
Treatment with specific prohibited medications or therapy beginning 4 weeks prior to screening and throughout the duration of the study
History of systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization
Pre-specified laboratory abnormalities at screening
Specific ocular characteristics in the study eye
Male subjects who are not surgically sterile and are not willing to practice a medically accepted method of birth control with their female partner of childbearing potential from screening through 30 days following completion of the study
Female subjects of childbearing potential who are not willing to practice a medically accepted method of birth control with their non-surgically sterile male sexual partner from screening through 30 days following completion of the study
Female subjects who are pregnant or lactating

Arm && Interventions

Group	Intervention	Description
Emixustat hydrochloride	emixustat hydrochloride	Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A) Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B) Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C) Week 4- Four emixustat HCl tablets (Strength C) All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.
Emixustat hydrochloride	Placebo	Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A) Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B) Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C) Week 4- Four emixustat HCl tablets (Strength C) All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.
Placebo	Placebo	Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm.

Primary Outcome Measures

Name	Time	Method
Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values	Baseline and 12 weeks	All values for IL-1β were below the lower limit of detection and were recorded as zero. Tests for IP-10 and MCP-1 failed accuracy and stability testing during assay development and were dropped from the study. The assay for PDGF-AA could not be developed.and results were not reported.

Secondary Outcome Measures