Pharmacokinetic and Pharmacodynamic Study of Emixustat in Subjects With Geographic Atrophy Associated With Dry Age-Related Macular Degeneration

Study Overview
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Brief Summary
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The purpose of this study is to characterize emixustat hydrochloride pharmacokinetic and pharmacodynamic parameters in subjects with geographic atrophy associated with dry age-related macular degeneration.

Detailed Description
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This is a multi-center, randomized, masked, multiple-dose, crossover study of the pharmacokinetics of emixustat hydrochloride (HCl) in subjects with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Subjects will receive study drug during multiple dose periods in a crossover design, and serve as their own controls. There is a 21-28 day washout period between dose periods. The final Study Exit visit is 21 to 28 days after the subject's last dose of study drug at the end of the final dosing period.

Official Title
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Pharmacokinetic and Pharmacodynamic Study of Emixustat Hydrochloride in Subjects With Geographic Atrophy Associated With Dry Age-Related Macular Degeneration

Conditions
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Geographic Atrophy, Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Emixustat HCl Tablet
* Other: Placebo Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females age ≥65 years Clinical diagnosis of GA associated with AMD Able and willing to provide written informed consent Able to reliably administer oral medication by self or with available assistance Exclusion Criteria: Geographic atrophy associated with a condition other than AMD History of, active or high risk of developing choroidal neovascularization (CNV) in either eye Known serious allergy to the fluorescein sodium for injection in angiography Pre-specified laboratory abnormalities at screening Treatment with any investigational study drug within 30 days of screening or device within 60 days of screening Prior participation in any clinical study of emixustat History of other disease, metabolic dysfunction, chronic immunosuppression, physical examination finding 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 21 days after the last dose of study drug

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Two dose periods in any sequence (subjects will be assigned to 1 of 2 possible sequences): Emixustat HCl Tablet Strength B (mid dose); 1 tablet once daily & 1 placebo tablet once daily for 7 days Emixustat HCl Tablet Strength A (low dose); 1 tablet twice daily for 7 days | Drug: Emixustat HCl Tablet<br>* Tablet for oral administration<br>* Other names: ACU-4429;Other: Placebo Tablet<br>* Tablet for oral administration<br>|
| Experimental: Cohort 2<br>Three dose periods in any sequence (subjects will be assigned to 1 of 6 possible sequences): Emixustat HCl Tablet Strength A (low dose); 1 tablet daily for 7 days Emixustat HCl Tablet Strength B (mid dose); 1 tablet daily for 7 days Emixustat HCl Tablet Strength C (high dose); 1 tablet daily for 7 days | Drug: Emixustat HCl Tablet<br>* Tablet for oral administration<br>* Other names: ACU-4429;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve from time zero to 24 hours [(AUC(0-24h)] |  | Day 1 and Day 7 of each dosing period | 
| Degree of suppression of the ERG b-wave response post-photobleaching. |  | Screening through Day 10 of each dosing period and study exit |