Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AKB-9778 Ophthalmic Solution

Study Overview
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Brief Summary
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The purpose of this Phase 1b study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of AKB-9778 ophthalmic solution (eye drops) administered for 7 days in adults. The study is a double-masked, multiple- ascending dose trial and will enroll four cohorts of up to 12 subjects. Dose cohorts will receive increasing doses of AKB-9778 ophthalmic solution or vehicle-matched placebo daily for 7 days. Cohort 5 will enroll subjects with open angle glaucoma or ocular hypertension who will continue current prostaglandin therapy during the study. Cohort 5 subjects will receive the maximum tolerated dose from the previous cohorts.

Official Title
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Phase 1 Multi Center, Double-Masked, Randomized, Placebo-Controlled, Multiple Ascending Dose Cohort Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single or Twice Daily Doses of AKB-9778 Ophthalmic Solution

Conditions
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Ocular Hypertension, Primary Open Angle Glaucoma

Intervention / Treatment
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* Drug: AKB-9778 Ophthalmic Solution
* Drug: Placebo Ophthalmic Solution


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Aged > 18 years to 70 years inclusive in Cohort 1; aged ≥ 45 to 70 years inclusive in Cohorts 2-4, aged 18 to 80 years inclusive in Cohort 5. For subjects in Cohort 1, IOP between 12 and 23 mm Hg (inclusive). For subjects in Cohorts 2-4, IOP between 16 and 23mm Hg (inclusive). For subjects in Cohort 5, IOP between 17 and 27 mm Hg (inclusive). Central corneal thickness of 480 to 600 μm, inclusive For subjects in Cohort 5, diagnosis of OAG or OHT For subjects in Cohort 5, currently receiving prostaglandin therapy for IOP lowering Key Exclusion Criteria: Diagnosis of any form of glaucoma in Cohorts 1-4 Clinically significant eye trauma within 6 months of screening Any intraocular ophthalmic procedure within 6 months of screening Any ocular inflammation within 90 days of screening or a history of recurrent uveitis in either eye Subjects with any known chronic ocular disease (other than incipient cataract or refractive error) Any condition preventing valid applanation tonometry measurement, e.g., clinically significant corneal disease, refractive surgery Visual acuity (VA) worse than 20/30 in either eye, For Cohort 5 VA worse than 20/100 in either eye

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKB-9778 Ophthalmic Solution<br>Up to 4 daily dose levels of AKB-9778 Ophthalmic Solution will be evaluated. Doses will be administered in both eyes daily for 7 days. | Drug: AKB-9778 Ophthalmic Solution<br>* AKB-9778 Ophthalmic Solution<br>|
| Placebo Comparator: Vehicle Control Ophthalmic Solution<br>Matched vehicle-control ophthalmic solution will be administered in both eyes daily for 7 days. | Drug: Placebo Ophthalmic Solution<br>* Matched vehicle-control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | Baseline to Day 7 | 
| Vital sign- systolic and diastolic blood pressure | Systolic and diastolic blood pressure in mmHg | Baseline to Day 7 | 
| Complete blood count | White blood cells with differential, hemoglobin, hematocrit and platelet count | Baseline to Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular pressure | Intraocular pressure in mmHg | Baseline to Day 7 | 
| AKB-9778 concentration | Measurement of AKB-9778 in plasma after drug administration | Baseline to Day 7 |