A Phase III Study Assessing the Efficacy and Safety of DE-117 Ophthalmic Solution Compared With Timolol Maleate Ophthalmic Solution 0.5% in Subjects With Glaucoma or Ocular Hypertension - Spectrum 3 Study

Study Overview
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Brief Summary
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This is a Phase III, randomized, double-masked, active-controlled, parallel-group, multi-center study. Subjects diagnosed with glaucoma or OHT who meet eligibility criteria at Visit 1 (Screening) will washout of their current topical IOP-lowering medication(s), if any. After completing the required washout period, subjects will return for Visit 2 (Baseline, Day 1). Subjects who meet all eligibility criteria at baseline will be randomized to receive double-masked treatment for 3 months. Adult subjects will receive open-label DE-117 Ophthalmic Solution for an additional 9 months. Approximately 400 adult subjects and up to 30 pediatric subjects with glaucoma or OHT who meet all eligibility criteria will be randomized in a 1:1 ratio to receive either: DE-117 Ophthalmic Solution once daily and Vehicle once daily, or Timolol Maleate Ophthalmic Solution 0.5% twice daily. The study will evaluate the efficacy and safety of DE-117 Ophthalmic Solution compared with Timolol Maleate Ophthalmic Solution 0.5% in subjects with glaucoma or OHT through Month 3 and will provide additional safety data through Month 12 for subjects receiving DE-117.

Official Title
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A Phase III, Randomized, Double-Masked, Active-Controlled, Parallel-Group, Multi-center Study Assessing the Efficacy and Safety of DE-117 Ophthalmic Solution Compared With Timolol Maleate Ophthalmic Solution 0.5% in Subjects With Glaucoma or Ocular Hypertension - Spectrum 3 Study

Conditions
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Glaucoma and Ocular Hypertension

Intervention / Treatment
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* Drug: DE-117 Ophthalmic Solution
* Drug: Timolol Maleate Ophthalmic Solution 0.5%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • glaucoma or ocular hypertension Exclusion Criteria: Females who are pregnant, nursing, or planning a pregnancy Any corneal abnormality or other condition interfering with or preventing reliable tonometric measurements

Ages Eligible for Study
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Minimum Age: 12 Months

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DE-117 Ophthalmic Solution<br>Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only | Drug: DE-117 Ophthalmic Solution<br>* Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only<br>|
| Active Comparator: Timolol Maleate Ophthalmic Solution 0.5%<br>Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only | Drug: Timolol Maleate Ophthalmic Solution 0.5%<br>* Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular Pressure at Week 1 | Intraocular Pressure (IOP), the fluid pressure inside the eye was measured with calibrated Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time points throughout the day. Analysis using Mixed-Effects Model for Repeated Measures (MMRM) | 08:00, 10:00 and 16:00 at Week 1 | 
| Intraocular Pressure at Week 6 | Intraocular Pressure (IOP), the fluid pressure inside the eye was measured with calibrated Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time points throughout the day. Analysis using Mixed-Effects Model for Repeated Measures (MMRM) | 08:00, 10:00 and 16:00 at Week 6 | 
| Intraocular Pressure at Month 3 | Intraocular Pressure (IOP), the fluid pressure inside the eye was measured with calibrated Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time points throughout the day. Analysis using Mixed-Effects Model for Repeated Measures (MMRM) | 08:00, 10:00 and 16:00 at Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Diurnal Intraocular Pressure (IOP) at Month 3 (First Key Secondary Endpoint) | Mean Diurnal Intraocular Pressure (IOP) at Month 3: Analysis using Mixed-Effects Model for Repeated Measures (MMRM) on observed cases. | Month 3 | 
| Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | Intraocular Pressure (IOP) at Week 1 with baseline mean diurnal IOP less than 25 mmHg (Second Key Secondary Endpoint) | 08:00, 10:00 and 16:00 at Week 1 | 
| Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | Intraocular Pressure (IOP) at Week 6 with baseline mean diurnal IOP less than 25 mmHg (Second Key Secondary Endpoint) | 08:00, 10:00 and 16:00 at Week 6 | 
| Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | Intraocular Pressure (IOP) at Month 3 with baseline mean diurnal IOP less than 25 mmHg (Second Key Secondary Endpoint) | 08:00, 10:00 and 16:00 at Month 3 | 
| Mean Diurnal Intraocular Pressure (IOP) at Week 1 (Third Key Secondary Endpoint) | Mean Diurnal Intraocular Pressure (IOP) at Week 1: Analysis using Mixed-Effects Model for Repeated Measures (MMRM) on observed cases. Mean Diurnal IOP at week 1 is defined as the average IOP of all three timepoints (8AM, 10AM and 4PM) at week 1. | Week 1 |