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. 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.
Interventions
Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months
Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months
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 (IOP) at Week 1 | 08:00, 10:00 and 16:00 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. |
| Intraocular Pressure (IOP) at Week 6 | 08:00, 10:00 and 16:00 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. |
| Intraocular Pressure (IOP) at Month 3 | 08:00, 10:00 and 16:00 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. |
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 | 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. |
| Mean Diurnal Intraocular Pressure (IOP) at Week 1 (Third Key Secondary Endpoint) | week 1 | 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. |
| 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 0.002% QD (20:00) and Vehicle QD (08:00) DE-117 0.002% QD in the evening (20:00) and vehicle QD in the morning (08:00). | 204 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) Timolol Maleate Ophthalmic Solution 0.5% Twice a day (20:00 & 08:00) | 205 |
| Total | 409 |
Baseline characteristics
| Characteristic | DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 115 Participants | 118 Participants | 233 Participants |
| Age, Categorical Between 18 and 65 years | 89 Participants | 87 Participants | 176 Participants |
| Age, Continuous | 64.0 years STANDARD_DEVIATION 11.43 | 64.8 years STANDARD_DEVIATION 11.56 | 64.4 years STANDARD_DEVIATION 11.49 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 8 Participants | 16 Participants |
| Race/Ethnicity, Customized Black or African American | 72 Participants | 54 Participants | 126 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 122 Participants | 140 Participants | 262 Participants |
| Region of Enrollment United States | 204 participants | 205 participants | 409 participants |
| Sex: Female, Male Female | 121 Participants | 109 Participants | 230 Participants |
| Sex: Female, Male Male | 83 Participants | 96 Participants | 179 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 204 | 0 / 205 |
| other Total, other adverse events | 68 / 204 | 49 / 205 |
| serious Total, serious adverse events | 7 / 204 | 1 / 205 |
Outcome results
Primary
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.
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 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Month 3 | 8:00 | 20.0 mmHg | Standard Error 0.22 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Month 3 | 10:00 | 19.4 mmHg | Standard Error 0.23 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Month 3 | 16:00 | 19.1 mmHg | Standard Error 0.23 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Month 3 | 16:00 | 19.0 mmHg | Standard Error 0.22 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Month 3 | 8:00 | 19.6 mmHg | Standard Error 0.22 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Month 3 | 10:00 | 18.9 mmHg | Standard Error 0.22 |
Primary
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.
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 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 1 | 8:00 | 19.4 mmHg | Standard Error 0.23 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 1 | 10:00 | 18.5 mmHg | Standard Error 0.22 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 1 | 16:00 | 17.9 mmHg | Standard Error 0.23 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 1 | 8:00 | 19.7 mmHg | Standard Error 0.23 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 1 | 10:00 | 18.9 mmHg | Standard Error 0.22 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 1 | 16:00 | 18.6 mmHg | Standard Error 0.22 |
Primary
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.
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 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 6 | 8:00 | 20.4 mmHg | Standard Error 0.22 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 6 | 10:00 | 19.5 mmHg | Standard Error 0.2 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 6 | 16:00 | 19.2 mmHg | Standard Error 0.21 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 6 | 8:00 | 19.5 mmHg | Standard Error 0.21 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 6 | 10:00 | 18.8 mmHg | Standard Error 0.2 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 6 | 16:00 | 18.8 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 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 18.9 mmHg | Standard Error 0.29 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 18.3 mmHg | Standard Error 0.28 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 18.1 mmHg | Standard Error 0.28 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 18.8 mmHg | Standard Error 0.27 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 18.0 mmHg | Standard Error 0.26 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 18.0 mmHg | Standard Error 0.26 |
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 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 18.3 mmHg | Standard Error 0.28 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 17.5 mmHg | Standard Error 0.27 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 17.0 mmHg | Standard Error 0.27 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 19.1 mmHg | Standard Error 0.26 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 18.2 mmHg | Standard Error 0.25 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 18.0 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 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 19.4 mmHg | Standard Error 0.28 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 18.6 mmHg | Standard Error 0.25 |
| DE-117 Ophthalmic Solution 0.002% QD (20:00) and Vehicle QD (08:00) | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 18.4 mmHg | Standard Error 0.26 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 8:00 | 18.9 mmHg | Standard Error 0.26 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 10:00 | 18.2 mmHg | Standard Error 0.24 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) | 16:00 | 18.0 mmHg | Standard Error 0.24 |
Secondary
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.
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 0.002% QD (20:00) and Vehicle QD (08:00) | Mean Diurnal Intraocular Pressure (IOP) at Month 3 (First Key Secondary Endpoint) | 19.5 mmHg | Standard Error 0.19 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Mean Diurnal Intraocular Pressure (IOP) at Month 3 (First Key Secondary Endpoint) | 19.2 mmHg | Standard Error 0.19 |
Secondary
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.
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 0.002% QD (20:00) and Vehicle QD (08:00) | Mean Diurnal Intraocular Pressure (IOP) at Week 1 (Third Key Secondary Endpoint) | 18.6 mmHg | Standard Error 0.2 |
| Timolol Maleate Ophthalmic Solution 0.5% BID (20:00 & 08:00) | Mean Diurnal Intraocular Pressure (IOP) at Week 1 (Third Key Secondary Endpoint) | 19.1 mmHg | Standard Error 0.2 |