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

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

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.

Study Overview

• Status: Completed
• Conditions: Ocular Hypertension (OHT); Mild Open Angle-glaucoma (OAG)
• Intervention / Treatment: Drug: Placebo; Drug: ONO-9054

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Costa Mesa, California, United States, 92626
      • Costa Mesa Clinical Site
    • Newport Beach, California, United States, 92663
      • Newport Beach (satellite site)
    • Santa Ana, California, United States, 92705
      • Santa Ana (satellite site)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm 1; Experimental Eye drops 3.0 µg/mL QD both eyes on Day 1, 5-18	Drug: ONO-9054
Experimental: Experimental Arm 2; Experimental Eye drops 10.0 µg/mL QD both eyes on Day 1, 5-18	Drug: ONO-9054
Experimental: Experimental Arm 3; Experimental Eye drop 30.0 µg/mL QD both eyes on day 1, 5-18	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	Drug: Placebo; Drug: ONO-9054
Placebo Comparator: Placebo Arm; Matched placebo eye drops dosed in same manner as ONO-9054	Drug: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ono Pharma USA Inc

Publications and helpful links

General Publications

• Berlin MS, Rowe-Rendleman C, Ahmed I, Ross DT, Fujii A, Ouchi T, Quach C, Wood A, Ward CL. EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study. Br J Ophthalmol. 2016 Jun;100(6):843-7. doi: 10.1136/bjophthalmol-2015-307000. Epub 2015 Oct 9.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: August 15, 2012
• First Submitted That Met QC Criteria: August 17, 2012
• First Posted (Estimate): August 22, 2012

Study Record Updates

• Last Update Posted (Estimate): June 3, 2013
• Last Update Submitted That Met QC Criteria: May 31, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Glaucoma; Eye diseases; ocular hypertension; OAG; OHT; ONO-9054; Open angle-glaucoma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension
• Other Study ID Numbers: ONO-9054IOU002