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 4 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. 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.

Official Title
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A Phase III, Randomized, Double-Masked, Active-Controlled, Parallel-Group, Multicenter 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 4 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 | Drug: DE-117 Ophthalmic Solution<br>* Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months<br>|
| Active Comparator: Timolol Maleate Ophthalmic Solution 0.5%<br>Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months | Drug: Timolol Maleate Ophthalmic Solution 0.5%<br>* Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular Pressure (IOP) at Week 1 | Intraocular Pressure: Analysis of IOP Score using Mixed Model for Repeated Measures (MMRM) on Observed Cases (Study Eye, Full Analysis Set). 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. | 08:00, 10:00 and 16:00 at Week 1 | 
| Intraocular Pressure (IOP) at Week 6 | Intraocular Pressure: Analysis of IOP Score using Mixed Model for Repeated Measures (MMRM) on Observed Cases (Study Eye, Full Analysis Set). 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. | 08:00, 10:00 and 16:00 at Week 6 | 
| Intraocular Pressure (IOP) at Month 3 | Intraocular Pressure: Analysis of IOP Score using Mixed Model for Repeated Measures (MMRM) on Observed Cases (Study Eye, Full Analysis Set). 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. | 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) | To determine if the mean diurnal IOP reduction with DE-117 ophthalmic solution 0.002% is superior to that of Timolol Maleate ophthalmic solution 0.5% at Month 3 in subjects with OAG or OHT. Mean Diurnal IOP is defined as the average IOP of all three timepoints (8AM, 10AM and 4PM) at Month 3. | 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) | The third key secondary endpoint, mean diurnal IOP at Week 1, the hypothesis of superiority of DE-117 to timolol was tested. Analysis using MMRM on Observed Cases. Mean Diurnal IOP is defined as the average IOP of all three timepoints (8AM, 10AM and 4PM) at week 1. | week 1 |