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

• Characterization of PK profiles [ Time Frame: up to 14 days ] [ Designated as safety issue: No ]
  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
• Evaluation of PD measurements [ Time Frame: up to 14 days ] [ Designated as safety issue: No ]
  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.
• Comparison of safety, tolerability between once daily morning and once daily evening [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  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.

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.

• Ocular Hypertension (OHT)
• Mild Open Angle-glaucoma (OAG)

• Drug: ONO-9054
• Drug: Placebo

• Experimental: Experimental Arm 1
  Experimental Eye drops 3.0 µg/mL QD both eyes on Day 1, 5-18
  Intervention: Drug: ONO-9054
• Experimental: Experimental Arm 2
  Experimental Eye drops 10.0 µg/mL QD both eyes on Day 1, 5-18
  Intervention: Drug: ONO-9054
• Experimental: Experimental Arm 3
  Experimental Eye drop 30.0 µg/mL QD both eyes on day 1, 5-18
  Intervention: Drug: ONO-9054
• Experimental: Experimental Arm 4
  Experimental Eye drop, 2 sequence crossover Cohort [1 dose; 1-30 µg/mL]to be determined and placebo
  Interventions:

  • Drug: ONO-9054
  • Drug: Placebo
• Placebo Comparator: Placebo Arm
  Matched placebo eye drops dosed in same manner as ONO-9054
  Intervention: Drug: Placebo

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