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

Study Overview
=================
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.

Official Title
-----------------
A Multicenter, Randomized, Double-Masked, Placebo-Controlled, Pilot Study to Evaluate Effects of Emixustat Hydrochloride on Aqueous Humor Biomarkers Associated With Proliferative Diabetic Retinopathy

Conditions
-----------------
Proliferative Diabetic Retinopathy

Intervention / Treatment
-----------------
* Drug: emixustat hydrochloride
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Emixustat hydrochloride<br>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. | Drug: emixustat hydrochloride<br>* Tablet for oral administration<br>* Other names: ACU-4429, Emixustat HCl;Other: Placebo<br>* Placebo tablets for oral administration contain only inactive ingredients<br>|
| Placebo Comparator: Placebo<br>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. | Other: Placebo<br>* Placebo tablets for oral administration contain only inactive ingredients<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Baseline and 12 weeks |