Glaucoma and Ocular Hypertension
Conditions
Brief summary
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.
Interventions
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
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
Sponsors
Santen Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Months to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressure at Week 1 | 08:00, 10:00 and 16:00 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) |
| Intraocular Pressure at Week 6 | 08:00, 10:00 and 16:00 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) |
| Intraocular Pressure at Month 3 | 08:00, 10:00 and 16:00 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Intraocular Pressure (IOP) at Month 3 with baseline mean diurnal IOP less than 25 mmHg (Second Key Secondary Endpoint) |
| Mean Diurnal Intraocular Pressure (IOP) at Month 3 (First Key Secondary Endpoint) | Month 3 | Mean Diurnal Intraocular Pressure (IOP) at Month 3: Analysis using Mixed-Effects Model for Repeated Measures (MMRM) on observed cases. |
| Mean Diurnal Intraocular Pressure (IOP) at Week 1 (Third Key Secondary Endpoint) | Week 1 | 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. |
| 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 1 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 Week 6 with baseline mean diurnal IOP less than 25 mmHg (Second Key Secondary Endpoint) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DE-117 Ophthalmic Solution 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
DE-117 Ophthalmic Solution: 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 | 212 |
| Timolol Maleate Ophthalmic Solution 0.5% 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
Timolol Maleate Ophthalmic Solution 0.5%: 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 | 213 |
| Total | 425 |
Baseline characteristics
| Characteristic | Total | DE-117 Ophthalmic Solution | Timolol Maleate Ophthalmic Solution 0.5% |
|---|---|---|---|
| Age, Categorical <=18 years | 13 Participants | 6 Participants | 7 Participants |
| Age, Categorical >=65 years | 238 Participants | 123 Participants | 115 Participants |
| Age, Categorical Between 18 and 65 years | 174 Participants | 83 Participants | 91 Participants |
| Age, Continuous | 64.1 years STANDARD_DEVIATION 14.69 | 64.7 years STANDARD_DEVIATION 14.91 | 63.5 years STANDARD_DEVIATION 14.48 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 100 Participants | 48 Participants | 52 Participants |
| Race/Ethnicity, Customized Multiple | 5 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 315 Participants | 160 Participants | 155 Participants |
| Region of Enrollment United States | 425 Participants | 212 Participants | 213 Participants |
| Sex: Female, Male Female | 258 Participants | 123 Participants | 135 Participants |
| Sex: Female, Male Male | 167 Participants | 89 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 211 | 1 / 215 | 1 / 377 |
| other Total, other adverse events | 61 / 211 | 47 / 215 | 85 / 377 |
| serious Total, serious adverse events | 4 / 211 | 5 / 215 | 12 / 377 |
Outcome results
Primary
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)
Time frame: 08:00, 10:00 and 16:00 at Month 3
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Month 3.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DE-117 Ophthalmic Solution | Intraocular Pressure at Month 3 | 8:00 | 19.7 mmHg | Standard Error 0.24 |
| DE-117 Ophthalmic Solution | Intraocular Pressure at Month 3 | 10:00 | 18.8 mmHg | Standard Error 0.21 |
| DE-117 Ophthalmic Solution | Intraocular Pressure at Month 3 | 16:00 | 18.6 mmHg | Standard Error 0.22 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure at Month 3 | 8:00 | 18.5 mmHg | Standard Error 0.24 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure at Month 3 | 10:00 | 17.7 mmHg | Standard Error 0.21 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure at Month 3 | 16:00 | 17.8 mmHg | Standard Error 0.21 |
Primary
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)
Time frame: 08:00, 10:00 and 16:00 at Week 1
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DE-117 Ophthalmic Solution | Intraocular Pressure at Week 1 | 8:00 | 19.0 mmHg | Standard Error 0.22 |
| DE-117 Ophthalmic Solution | Intraocular Pressure at Week 1 | 10:00 | 18.0 mmHg | Standard Error 0.21 |
| DE-117 Ophthalmic Solution | Intraocular Pressure at Week 1 | 16:00 | 17.5 mmHg | Standard Error 0.21 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure at Week 1 | 8:00 | 19.1 mmHg | Standard Error 0.21 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure at Week 1 | 10:00 | 18.2 mmHg | Standard Error 0.21 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure at Week 1 | 16:00 | 17.9 mmHg | Standard Error 0.21 |
Primary
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)
Time frame: 08:00, 10:00 and 16:00 at Week 6
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 6.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DE-117 Ophthalmic Solution | Intraocular Pressure at Week 6 | 8:00 | 19.8 mmHg | Standard Error 0.2 |
| DE-117 Ophthalmic Solution | Intraocular Pressure at Week 6 | 10:00 | 18.9 mmHg | Standard Error 0.2 |
| DE-117 Ophthalmic Solution | Intraocular Pressure at Week 6 | 16:00 | 18.5 mmHg | Standard Error 0.21 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure at Week 6 | 8:00 | 18.4 mmHg | Standard Error 0.2 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure at Week 6 | 10:00 | 18.0 mmHg | Standard Error 0.2 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure at Week 6 | 16:00 | 17.7 mmHg | Standard Error 0.21 |
Secondary
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)
Time frame: 08:00, 10:00 and 16:00 at Month 3
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Month 3.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DE-117 Ophthalmic Solution | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 18.6 mmHg | Standard Error 0.29 |
| DE-117 Ophthalmic Solution | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 17.8 mmHg | Standard Error 0.25 |
| DE-117 Ophthalmic Solution | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 17.7 mmHg | Standard Error 0.25 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 17.7 mmHg | Standard Error 0.28 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 16.9 mmHg | Standard Error 0.25 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 17.2 mmHg | Standard Error 0.25 |
Secondary
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)
Time frame: 08:00, 10:00 and 16:00 at Week 1
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DE-117 Ophthalmic Solution | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 17.9 mmHg | Standard Error 0.25 |
| DE-117 Ophthalmic Solution | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 17.2 mmHg | Standard Error 0.24 |
| DE-117 Ophthalmic Solution | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 16.8 mmHg | Standard Error 0.25 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 18.2 mmHg | Standard Error 0.25 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 17.3 mmHg | Standard Error 0.24 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 17.2 mmHg | Standard Error 0.25 |
Secondary
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)
Time frame: 08:00, 10:00 and 16:00 at Week 6
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 6.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DE-117 Ophthalmic Solution | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 18.7 mmHg | Standard Error 0.24 |
| DE-117 Ophthalmic Solution | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 18.0 mmHg | Standard Error 0.25 |
| DE-117 Ophthalmic Solution | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 17.6 mmHg | Standard Error 0.23 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 17.8 mmHg | Standard Error 0.24 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 17.4 mmHg | Standard Error 0.25 |
| Timolol Maleate Ophthalmic Solution 0.5% | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 17.1 mmHg | Standard Error 0.23 |
Secondary
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.
Time frame: Month 3
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Month 3.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DE-117 Ophthalmic Solution | Mean Diurnal Intraocular Pressure (IOP) at Month 3 (First Key Secondary Endpoint) | 19.0 mmHg | Standard Error 0.2 |
| Timolol Maleate Ophthalmic Solution 0.5% | Mean Diurnal Intraocular Pressure (IOP) at Month 3 (First Key Secondary Endpoint) | 18.0 mmHg | Standard Error 0.19 |
Secondary
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.
Time frame: Week 1
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 1.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DE-117 Ophthalmic Solution | Mean Diurnal Intraocular Pressure (IOP) at Week 1 (Third Key Secondary Endpoint) | 18.1 mmHg | Standard Error 0.19 |
| Timolol Maleate Ophthalmic Solution 0.5% | Mean Diurnal Intraocular Pressure (IOP) at Week 1 (Third Key Secondary Endpoint) | 18.4 mmHg | Standard Error 0.19 |