Single and Multiple Dose Escalation and Two-sequence Crossover Study of ONO-9054 in Patients With Ocular Hypertension or Mild Open-angle Glaucoma

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and tolerability of 3 planned doses of ONO-9054 in the eyes of adult male and female patients with ocular hypertension (OHT) or mild open angle-glaucoma (OAG). The secondary objectives are to evaluate Pharmacodynamics (PD) and to characterize the pharmacokinetic (PK) profile of ONO-9054 and its metabolite in plasma and to compare its tolerability following morning and evening dosing.

Official Title
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A Double-masked, Placebo-controlled, Dose-escalation Study and Double-masked, Two-sequence, Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ONO-9054 in Patients With Ocular Hypertension or Mild Open-Angle Glaucoma

Conditions
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Ocular Hypertension (OHT), Mild Open Angle-glaucoma (OAG)

Intervention / Treatment
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* Drug: ONO-9054
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects age 18-80 (inclusive) with confirmed diagnosis of OHT or OAG Confirmed diagnosis of bilateral OHT or chronic open-angle glaucoma Able to undergo washout of all ocular drugs An IOP ≥ 22mmHg at 8:00 AM and ≥ 21 mmHg at 10:00 AM in at least one eye; but ≤ 35 mmHg at all time points in both eyes on Day -2 and Day -1 Central corneal thickness 500-600 µm at screening in both eyes BCVA 20/100 or better in both eyes Exclusion Criteria: Any history of severe ocular trauma in either eye at any time Any history of previous intraocular or ocular laser surgery within the past 3 months or any refractive surgery procedure within the past 6 months of screening visit in the study eye(s) Cataracts that prevent observation of the fundus in either eye

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm 1<br>Experimental Eye drops 3.0 µg/mL QD both eyes on Day 1, 5-18 | Drug: ONO-9054<br> <br> |
| Experimental: Experimental Arm 2<br>Experimental Eye drops 10.0 µg/mL QD both eyes on Day 1, 5-18 | Drug: ONO-9054<br> <br> |
| Experimental: Experimental Arm 3<br>Experimental Eye drop 30.0 µg/mL QD both eyes on day 1, 5-18 | Drug: ONO-9054<br> <br> |
| Experimental: Experimental Arm 4<br>Experimental Eye drop, 2 sequence crossover Cohort [1 dose; 1-30 µg/mL]to be determined and placebo | Drug: ONO-9054<br> <br> Drug: Placebo<br> <br> |
| Placebo Comparator: Placebo Arm<br>Matched placebo eye drops dosed in same manner as ONO-9054 | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of ONO-9054 | Safety and tolerability of ONO-9054 will be measured using vital signs, ECGs, laboratory tests, ocular exams, physical examination and incidence/severity of adverse events over a dosing period of up to 14 days | up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of PK profiles | The mean concentrations of ONO-9054 and its active metabolite will be measured in plasma in order to determine peak and trough levels over a dosing period of 14 days | up to 14 days | 
| Evaluation of PD measurements | The pharmacodynamic measurement will be intraocular pressure. Relative changes with respect to baseline will be assessed after 14 days of administration under both AM and PM dosing conditions. | up to 14 days | 
| Comparison of safety, tolerability between once daily morning and once daily evening | Safety and tolerability of a single concentration will be evaluated by review of adverse events and any change from baseline in ocular symptoms in a crossover arm in which the active drug is administered for 14 days under both AM and PM dosing conditions. | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ONO-9054, ocular hypertension, OHT, Open angle-glaucoma, OAG, Glaucoma, Eye diseases