Primary Open Angle Glaucoma, Ocular Hypertension
Conditions
Keywords
Primary open angle glaucoma, Ocular hypertension
Brief summary
This is a Phase 3 study to evaluate the safety and efficacy of T-2345 dosed to one of both eyes once daily for 84 days compared to Xalatan dosed to one of both eyes once daily for 84 days in patients with elevated eye pressure.
Detailed description
The objective of this Phase 3 study is to evaluate the efficacy and safety of T-2345 nonpreserved ophthalmic solution (latanoprost 0.005%) in comparison to Xalatan® (latanoprost 0.005%) in subjects with primary open angle glaucoma (POAG) or ocular hypertension (OH). This will be a randomized, multicenter, parallel-group, observer-masked study in approximately 380 evaluable subjects treated for 84 days. Subjects will have a history of POAG or OH and elevated intraocular pressure (IOP) and will have been adequately controlled (IOP ≤ 18 mm Hg) on latanoprost 0.005% ophthalmic solution monotherapy for at least 4 weeks. Primary efficacy (IOP) will be assessed in the study eye at each visit by Goldmann applanation tonometry at all assessment visits. Safety will be assessed at each visit by corrected Snellen Visual Acuity, slit lamp examination/anterior chamber cell count and flare and adverse event (AE) collection. Primary Efficacy Endpoint is the between-group comparison of the mean IOP values at each time point at each of the Day 15, 42, and 84 visits. Secondary Efficacy Endpoints include: * Between-group comparison of the mean change from baseline in diurnal IOP measurements at all postbaseline visits. * Between-group comparison of the mean change from baseline in IOP measurements at all times points at Day 15, Day 42 and Day 84.
Interventions
DRUGT-2345
T-2345 Ophthalmic Solution
DRUGXalatan
Xalatan (latanoprost 0.005% ophthalmic solution)
Sponsors
Nephron Pharmaceuticals Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older. 2. POAG or OH with IOP treated and adequately controlled (IOP ≤ 18 mm Hg) with latanoprost 0.005% ophthalmic solution monotherapy for at least 4 weeks prior to Screening. 3. Each eye being treated with latanoprost 0.005% ophthalmic solution monotherapy must have mean IOP ≤ 18 mm Hg at Screening and mean IOP ≤ 28 mm Hg at Baseline; measurements will be taken at each visit at 8 AM, 10 AM, and 4 PM (each ± 30 minutes) with AM measurements of IOP at least 2 hours apart. If only one eye qualifies but both eyes have glaucoma and the fellow eye will require antiglaucoma medications, the subject does not qualify for the trial. 4. Stable visual field (VF), defined as no sign of VF degradation between two consecutive 30-2 or two consecutive 24-2 VF examinations. For subjects with no VF defect (eg, those with OH), a single, normal VF examination performed ˂ 6 months prior to the screening visit is allowed to determine eligibility. For patients who have an abnormal VF examination, the following criteria apply: * Two VF (most recent VF and past VF) examinations performed at least ≥ 6 months and ≤ 18 months apart must be compared; * The most recent VF examination should be performed \< 6 months prior to the Screening visit; * The past VF examination should be performed ≥ 6 months and ≤ 18 months prior to the most recent VF test. 5. Stable corrected Snellen visual acuity (VA) of better than 20/200 in the study eye. Patients must see ≥ 50% of the letters on a single line to accept that VA line. 6. Central corneal thickness 480-620 μm in the study eye. 7. Shaffer gonioscopic grade of ≥ 3 (in at least 3 quadrants) in both eyes. 8. Female subjects must be 1-year postmenopausal, surgically sterilized, or women of childbearing potential with a negative urine pregnancy test at Screening. Women of childbearing potential must use an acceptable form of contraception throughout the study. Acceptable methods include the use of at least one of the following: intrauterine (intrauterine device), hormonal (oral, injection, patch, implant, ring), barrier with spermicide (condom, diaphragm), or abstinence. 9. All subjects must provide signed written consent prior to participation in any study-related procedures.
Exclusion criteria
In the study eye: 1. A mean deviation of \< -20 dB on VF examination. 2. A mean IOP ˃ 28 mm Hg at Baseline. 3. Presence of a scotoma within 5° of fixation on VF examination. 4. Aphakia. 5. Use of any antiglaucoma medication in addition to latanoprost 0.005% ophthalmic solution within 2 weeks prior to Screening and any antiglaucoma medication (other than latanoprost) during the study period other than the randomized study medication. 6. Use of any topical ophthalmic steroid within 2 weeks prior to Baseline. A short course of oral steroids is acceptable if the course is completed \> 2 weeks prior to Screening. Inhaled and intranasal steroids are acceptable. 7. Use of topical nonsteroidal anti-inflammatory drug (NSAID) within 2 weeks prior to Baseline. 8. Use of any ophthalmic medications during the study period (nonpreserved artificial tears are allowed). 9. Ocular surgery or laser treatment of any kind in the study eye within 3 months prior to Baseline. 10. History of ocular allergy/inflammation and/or severe blepharitis and/or uveitis. Seasonal allergic conjunctivitis is acceptable (avoid enrollment of subjects who may experience seasonal flare-up during the study period). Mild blepharitis/blepharoconjunctivitis, typically associated with prostaglandin usage, on the lid is acceptable. 11. History of ocular trauma or ocular infection within 3 months of Screening. 12. History of herpes simplex keratitis. 13. Current proliferative diabetic retinopathy or age-related macular degeneration, unless deemed not clinically significant by the Investigator. 14. Severe dry eye (eg, clinically relevant superficial punctate keratitis, epithelial erosions of the cornea, and/or use of dry eye medication \[including artificial tears\] with a frequency exceeding 8 instillations per day). 15. Contact lens wear during the study period. Contact lens wear in an untreated fellow eye is allowed. 16. Any secondary glaucoma or OH (eg, congenital glaucoma, closed-angle glaucoma, uveitic glaucoma, or pseudoexfoliation syndrome). 17. Any severe glaucoma defined by cupping (cup-to-disc ratio ≥ 0.8). 18. Any non-laser glaucoma surgery. 19. Any abnormality preventing accurate assessment (eg, resulting in unreliable applanation tonometry or VF examination). General: 20. Pregnancy or lactation. 21. Uncontrolled asthma (defined as asthma that does not respond to the maximum guideline-directed therapy). 22. Allergy to benzalkonium chloride. 23. History of moderate or severe renal or hepatic impairment. 24. Participation in any study of an investigational product within 30 days prior to Screening or at any time during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressure | Measured at 8am 10 am and 4 pm at Baseline and on Days 15, 42 and 84 | Evaluation of intraocular pressure using Goldmann applanation tonometry. Primary outcome was the between group difference in the change from baseline in IOP at each of 9 assessment points. Equivalence was achieved if the 95% Confidence Intervals were within 1.5 mmHg at all 9 time points |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity | Baseline and 84 days | Visual Acuity was measured using the Corrected Snellen Visual Acuity method reported as the Logarithm Minimum Angle of Resoution (logMAR) change from baseline. The Snellen eye chart was used with the subject's current corrected lens prescription at a distance equivalent to 20 feet. Results from the Snellen chart were converted to the logMAR scale which is the standard tool for reporting visual acuity outcomes. |
| Slit Lamp Examination | Baseline and 84 days | Number of participants with eye abnormalities following routine slit lamp examination. The anterior segment of the eye including lids, cornea, conjunctiva, anterior chamber, iris and lens were evaluated with a routine slit lamp examination and any abnormalities observed were reported. |
| Ophthalmoscopy | Baseline and 84 days | Number of participants with eye abnormalities following ophthalmoscopy. Direct ophthalmoscopy with dilation included assessment of the optic nerve head for pallor and cupping. A dilated fundus examination consisting of the vitreous, optic nerve, macula, and peripheral retina was conducted. Results are reported as the number of subjects with clinical significant abnormalities at Day 84 that were not clinically significant at Baseline. |
| Mean Deviation in Visual Field | Baseline and 84 days | Visual Field was performed using an automated perimeter according to the sites standard protocol. This test measures the angle of the visual field from the central visual axis. Visual Field Testing generates a numerical scale as its main result which shows the retinal sensitivities at the different test locations, expressed in Decibels (dB). The mean deviation in the visual field reflects the overall depression (deviation from normal values). Negative values indicate a reduction in visual field. The analysis performed is the mean change from baseline at Day 84. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| T-2345 T-2345 Ophthalmic Solution | 164 |
| Xalatan Xalatan (Latanoprost 0.005% Ophthalmic Solution) | 170 |
| Total | 334 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Ran out of IP and decided to discontinue | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | T-2345 | Xalatan | Total |
|---|---|---|---|
| Age, Continuous | 67.1 Years STANDARD_DEVIATION 10.2 | 66.1 Years STANDARD_DEVIATION 11 | 66.5 Years STANDARD_DEVIATION 10.6 |
| Corneal thickness, fellow eye (μm) | 552.1 μm STANDARD_DEVIATION 33.7 | 549.4 μm STANDARD_DEVIATION 33.6 | 550.7 μm STANDARD_DEVIATION 33.6 |
| Corneal thickness, study eye (μm) | 550.7 μm STANDARD_DEVIATION 33.9 | 548.7 μm STANDARD_DEVIATION 34.5 | 549.6 μm STANDARD_DEVIATION 34.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 22 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 146 Participants | 148 Participants | 294 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 37 Participants | 28 Participants | 65 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 125 Participants | 141 Participants | 266 Participants |
| Region of Enrollment United States | 164 participants | 170 participants | 334 participants |
| Sex: Female, Male Female | 104 Participants | 100 Participants | 204 Participants |
| Sex: Female, Male Male | 60 Participants | 70 Participants | 130 Participants |
| Shaffer angle by gonioscopy, fellow eye Schaffer Angle Grade III | 83 Participants | 84 Participants | 167 Participants |
| Shaffer angle by gonioscopy, fellow eye Schaffer Angle Grade IV | 81 Participants | 86 Participants | 167 Participants |
| Shaffer angle by gonioscopy, study eye Schaffer Angle Grade III | 83 Participants | 84 Participants | 167 Participants |
| Shaffer angle by gonioscopy, study eye Schaffer Angle Grade IV | 81 Participants | 86 Participants | 167 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 165 | 1 / 169 |
| other Total, other adverse events | 23 / 165 | 44 / 169 |
| serious Total, serious adverse events | 1 / 165 | 4 / 169 |
Outcome results
Primary
Intraocular Pressure
Evaluation of intraocular pressure using Goldmann applanation tonometry. Primary outcome was the between group difference in the change from baseline in IOP at each of 9 assessment points. Equivalence was achieved if the 95% Confidence Intervals were within 1.5 mmHg at all 9 time points
Time frame: Measured at 8am 10 am and 4 pm at Baseline and on Days 15, 42 and 84
Population: The Per Protocol population was the primary efficacy population and consisted of those subjects in the ITT population who had no major protocol violations and no missing data points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-2345 | Intraocular Pressure | Day 84 08:00 | -3.0 mm Hg | Standard Deviation 3.2 |
| T-2345 | Intraocular Pressure | Day 15 10:00 | -2.7 mm Hg | Standard Deviation 2.9 |
| T-2345 | Intraocular Pressure | Day 42 16:00 | -2.3 mm Hg | Standard Deviation 2.9 |
| T-2345 | Intraocular Pressure | Day 15 16:00 | -2.3 mm Hg | Standard Deviation 2.8 |
| T-2345 | Intraocular Pressure | Day 84 10:00 | -2.7 mm Hg | Standard Deviation 3 |
| T-2345 | Intraocular Pressure | Day 42 08:00 | -3.0 mm Hg | Standard Deviation 3.2 |
| T-2345 | Intraocular Pressure | Day 15 08:00 | -3.0 mm Hg | Standard Deviation 3.2 |
| T-2345 | Intraocular Pressure | Day 42 10:00 | -2.7 mm Hg | Standard Deviation 3.1 |
| T-2345 | Intraocular Pressure | Day 84 16:00 | -2.2 mm Hg | Standard Deviation 2.8 |
| Xalatan | Intraocular Pressure | Day 42 10:00 | -3.5 mm Hg | Standard Deviation 3.4 |
| Xalatan | Intraocular Pressure | Day 84 16:00 | -2.9 mm Hg | Standard Deviation 3.2 |
| Xalatan | Intraocular Pressure | Day 84 10:00 | -3.6 mm Hg | Standard Deviation 3.1 |
| Xalatan | Intraocular Pressure | Day 42 16:00 | -3.1 mm Hg | Standard Deviation 3.4 |
| Xalatan | Intraocular Pressure | Day 84 08:00 | -3.5 mm Hg | Standard Deviation 3.2 |
| Xalatan | Intraocular Pressure | Day 15 08:00 | -3.8 mm Hg | Standard Deviation 3.4 |
| Xalatan | Intraocular Pressure | Day 15 10:00 | -3.6 mm Hg | Standard Deviation 3.3 |
| Xalatan | Intraocular Pressure | Day 15 16:00 | -3.1 mm Hg | Standard Deviation 3.3 |
| Xalatan | Intraocular Pressure | Day 42 08:00 | -3.5 mm Hg | Standard Deviation 3.2 |
Comparison: The primary endpoint was measured at 9 separate assessment times (3 time points over a 12 hour period on 3 separate days. The primary analysis was based on a comparison of the IOP change from baseline between the two arms at each assessment.The equivalence margin was tested using an analysis of covariance on change from baseline with pooled site and baseline as a factor. Equivalence was considered to be met if the 95% confidence intervals were within 1.5 mmHg at each of the 9 assessment points.p-value: 0.009195% CI: [0.195, 1.366]ANCOVA
Comparison: The primary endpoint was measured at 9 separate assessment times (3 time points over a 12 hour period on 3 separate days. The primary analysis was based on a comparison of the IOP change from baseline between the two arms at each assessment.The equivalence margin was tested using an analysis of covariance on change from baseline with pooled site and baseline as a factor. Equivalence was considered to be met if the 95% confidence intervals were within 1.5 mmHg at each of the 9 assessment points.p-value: 0.009895% CI: [0.161, 1.167]ANCOVA
Comparison: The primary endpoint was measured at 9 separate assessment times (3 time points over a 12 hour period on 3 separate days. The primary analysis was based on a comparison of the IOP change from baseline between the two arms at each assessment.The equivalence margin was tested using an analysis of covariance on change from baseline with pooled site and baseline as a factor. Equivalence was considered to be met if the 95% confidence intervals were within 1.5 mmHg at each of the 9 assessment points.p-value: 0.039895% CI: [0.025, 1.058]ANCOVA
Comparison: The primary endpoint was measured at 9 separate assessment times (3 time points over a 12 hour period on 3 separate days. The primary analysis was based on a comparison of the IOP change from baseline between the two arms at each assessment.The equivalence margin was tested using an analysis of covariance on change from baseline with pooled site and baseline as a factor. Equivalence was considered to be met if the 95% confidence intervals were within 1.5 mmHg at each of the 9 assessment points.p-value: 0.100895% CI: [-0.093, 1.05]ANCOVA
Comparison: The primary endpoint was measured at 9 separate assessment times (3 time points over a 12 hour period on 3 separate days. The primary analysis was based on a comparison of the IOP change from baseline between the two arms at each assessment.The equivalence margin was tested using an analysis of covariance on change from baseline with pooled site and baseline as a factor. Equivalence was considered to be met if the 95% confidence intervals were within 1.5 mmHg at each of the 9 assessment points.p-value: 0.055895% CI: [-0.013, 1.024]ANCOVA
Comparison: The primary endpoint was measured at 9 separate assessment times (3 time points over a 12 hour period on 3 separate days. The primary analysis was based on a comparison of the IOP change from baseline between the two arms at each assessment.The equivalence margin was tested using an analysis of covariance on change from baseline with pooled site and baseline as a factor. Equivalence was considered to be met if the 95% confidence intervals were within 1.5 mmHg at each of the 9 assessment points.p-value: 0.049195% CI: [0.002, 1.074]ANCOVA
Comparison: The primary endpoint was measured at 9 separate assessment times (3 time points over a 12 hour period on 3 separate days. The primary analysis was based on a comparison of the IOP change from baseline between the two arms at each assessment.The equivalence margin was tested using an analysis of covariance on change from baseline with pooled site and baseline as a factor. Equivalence was considered to be met if the 95% confidence intervals were within 1.5 mmHg at each of the 9 assessment points.p-value: 0.002595% CI: [0.286, 1.329]ANCOVA
Comparison: The primary endpoint was measured at 9 separate assessment times (3 time points over a 12 hour period on 3 separate days. The primary analysis was based on a comparison of the IOP change from baseline between the two arms at each assessment.The equivalence margin was tested using an analysis of covariance on change from baseline with pooled site and baseline as a factor. Equivalence was considered to be met if the 95% confidence intervals were within 1.5 mmHg at each of the 9 assessment points.p-value: 0.011395% CI: [0.143, 1.111]ANCOVA
Comparison: The primary endpoint was measured at 9 separate assessment times (3 time points over a 12 hour period on 3 separate days. The primary analysis was based on a comparison of the IOP change from baseline between the two arms at each assessment.The equivalence margin was tested using an analysis of covariance on change from baseline with pooled site and baseline as a factor. Equivalence was considered to be met if the 95% confidence intervals were within 1.5 mmHg at each of the 9 assessment points.p-value: 0.064995% CI: [-0.063, 0.975]ANCOVA
Secondary
Mean Deviation in Visual Field
Visual Field was performed using an automated perimeter according to the sites standard protocol. This test measures the angle of the visual field from the central visual axis. Visual Field Testing generates a numerical scale as its main result which shows the retinal sensitivities at the different test locations, expressed in Decibels (dB). The mean deviation in the visual field reflects the overall depression (deviation from normal values). Negative values indicate a reduction in visual field. The analysis performed is the mean change from baseline at Day 84.
Time frame: Baseline and 84 days
Population: Safety population defined as all randomized subjects who received at least one dose of the allocated study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-2345 | Mean Deviation in Visual Field | Study eye | -0.169 Decibels (dB) | Standard Deviation 1.607 |
| T-2345 | Mean Deviation in Visual Field | Fellow eye | 0.067 Decibels (dB) | Standard Deviation 2.124 |
| Xalatan | Mean Deviation in Visual Field | Study eye | -0.166 Decibels (dB) | Standard Deviation 1.68 |
| Xalatan | Mean Deviation in Visual Field | Fellow eye | -0.094 Decibels (dB) | Standard Deviation 1.466 |
Secondary
Ophthalmoscopy
Number of participants with eye abnormalities following ophthalmoscopy. Direct ophthalmoscopy with dilation included assessment of the optic nerve head for pallor and cupping. A dilated fundus examination consisting of the vitreous, optic nerve, macula, and peripheral retina was conducted. Results are reported as the number of subjects with clinical significant abnormalities at Day 84 that were not clinically significant at Baseline.
Time frame: Baseline and 84 days
Population: Safety population defined as all randomized subjects who received at least one dose of the allocated study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| T-2345 | Ophthalmoscopy | Study eye | 1 Participants |
| T-2345 | Ophthalmoscopy | Fellow eye | 1 Participants |
| Xalatan | Ophthalmoscopy | Study eye | 0 Participants |
| Xalatan | Ophthalmoscopy | Fellow eye | 0 Participants |
Secondary
Slit Lamp Examination
Number of participants with eye abnormalities following routine slit lamp examination. The anterior segment of the eye including lids, cornea, conjunctiva, anterior chamber, iris and lens were evaluated with a routine slit lamp examination and any abnormalities observed were reported.
Time frame: Baseline and 84 days
Population: Safety population defined as all randomized subjects who received at least one dose of the allocated study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| T-2345 | Slit Lamp Examination | Cornea | 1 Participants |
| T-2345 | Slit Lamp Examination | Iris | 0 Participants |
| T-2345 | Slit Lamp Examination | Conjunctiva | 2 Participants |
| T-2345 | Slit Lamp Examination | Lens | 3 Participants |
| T-2345 | Slit Lamp Examination | Lid | 4 Participants |
| Xalatan | Slit Lamp Examination | Lens | 6 Participants |
| Xalatan | Slit Lamp Examination | Lid | 0 Participants |
| Xalatan | Slit Lamp Examination | Cornea | 2 Participants |
| Xalatan | Slit Lamp Examination | Conjunctiva | 2 Participants |
| Xalatan | Slit Lamp Examination | Iris | 1 Participants |
Secondary
Visual Acuity
Visual Acuity was measured using the Corrected Snellen Visual Acuity method reported as the Logarithm Minimum Angle of Resoution (logMAR) change from baseline. The Snellen eye chart was used with the subject's current corrected lens prescription at a distance equivalent to 20 feet. Results from the Snellen chart were converted to the logMAR scale which is the standard tool for reporting visual acuity outcomes.
Time frame: Baseline and 84 days
Population: Safety population defined as all randomized subjects who received at least one dose of the allocated study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| T-2345 | Visual Acuity | -0.003 logMAR units | Standard Deviation 0.075 |
| Xalatan | Visual Acuity | -0.008 logMAR units | Standard Deviation 0.082 |