Ocular Hypertension, Open-angle Glaucoma
Conditions
Brief summary
This study was to compare the safety and efficacy of the preservative-free formulation of 0.0015% MK2452 (tafluprost) and preservative-free 0.5% timolol maleate in patients with open-angle glaucoma and ocular hypertension. This study was to demonstrate that the preservative-free formulation of 0.0015% tafluprost is non-inferior to preservative-free 0.5% timolol maleate.
Interventions
DRUGPreservative-Free Tafluprost
One drop of preservative-free vehicle per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for 12 weeks
DRUGComparator: timolol
One drop of preservative-free timolol maleate (0.5%) per eye twice daily for 12 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has been diagnosed with primary open-angle glaucoma, pigmentary glaucoma, capsular glaucoma/pseudoexfoliation, or ocular hypertension * Patient has a mean (or median) IOP of \>=23 and =\<36 in at least one eye at the 0800 hours time point at the Baseline Visit. * Patient has \<5 mmHg difference in mean (or median) IOP between eyes at each time point (0800 hours, 1000 hours, and 1600 hours) at Baseline. * Patient is currently using a prescribed ocular hypotensive medication and has been on a stable dose for 30 days prior to screening, or patient is drug-naive (those who have never used or who have not used ocular hypotensive medication for at least 4 weeks prior to screening) * Patient is able to safely discontinue current ocular hypotensive medication during up to the 4-week washout period * Patient has vision corrected to 20/80 or better in each eye * Patient is willing and able to avoid wearing contact lenses from 4 weeks prior to dosing through 24 hour after final dosing * Patient is willing and able to self-administer or has an able person available on a daily basis to assist with administration of study medications * Patient is not pregnant and not planning to become pregnant during the study * Patient is male or female ≥18 of age on the day of signing the informed consent
Exclusion criteria
* Patient is unable to use study medication in the affected eye(s) * Patient has a history of inflammatory ocular surface disease or anterior or posterior uveitis in either eye * Patient has a history of retinal detachment, diabetic retinopathy, or other progressive retinal disease * Patient has experienced significant visual field loss within the last year * Patient has had intraocular surgery in either eye in the last 4 months * Patient has a history of glaucoma surgery or refractive surgery in either eye * Patient is currently taking two or more anti-glaucoma medications (except Cosopt™ or its generic formulation) * Patient has previously used tafluprost * Patient has a history of cardiovascular disorder within 6 months prior to screening * Patient has a history of bronchial asthma, wheezing, pneumonia, COPD, other pulmonary disease, or abnormal chest x-ray * Patient has a mean (or median) IOP \>36 mmHg in either eye at the Screening Visit or at any time point (0800 hours, 1000 hours, and 1600 hours) of the Baseline Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Baseline, Weeks 2, 6, and 12. | IOP was measured using a Goldmann applanation tonometer. The primary evaluation was based on the study eye (the worse eye based on the 0800 hour IOP baseline or the right eye when both eyes had the same IOP). IOP change from baseline was calculated using the baseline IOP at each time point (0800 hours at baseline to 0800 hours at Week 2, 6, and 12; 1000 hours at baseline to 1000 hours at Week 2, 6, and 12; 1600 hours at baseline to 1600 hours at Week 2, 6, and 12). Lowering elevated IOP is a treatment goal of glaucoma. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Baseline IOP | Baseline | IOP was measured using a Goldmann applanation tonometer. The primary evaluation was based on the study eye (the worse eye based on the 0800 hour IOP baseline or the right eye when both eyes had the same IOP). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tafluprost One drop of preservative-free vehicle per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for 12 weeks. | 320 |
| Timolol Maleate One drop of preservative-free timolol maleate (0.5%) per eye twice daily for 12 weeks. | 323 |
| Total | 643 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 5 |
Baseline characteristics
| Characteristic | Tafluprost | Timolol Maleate | Total |
|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 11.7 | 63.3 years STANDARD_DEVIATION 11.6 | 63.3 years STANDARD_DEVIATION 11.6 |
| Sex: Female, Male Female | 183 Participants | 192 Participants | 375 Participants |
| Sex: Female, Male Male | 137 Participants | 131 Participants | 268 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 320 | 0 / 323 |
| serious Total, serious adverse events | 2 / 320 | 7 / 323 |
Outcome results
Primary
Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12)
IOP was measured using a Goldmann applanation tonometer. The primary evaluation was based on the study eye (the worse eye based on the 0800 hour IOP baseline or the right eye when both eyes had the same IOP). IOP change from baseline was calculated using the baseline IOP at each time point (0800 hours at baseline to 0800 hours at Week 2, 6, and 12; 1000 hours at baseline to 1000 hours at Week 2, 6, and 12; 1600 hours at baseline to 1600 hours at Week 2, 6, and 12). Lowering elevated IOP is a treatment goal of glaucoma.
Time frame: Baseline, Weeks 2, 6, and 12.
Population: The Per-Protocol (PP) approach excluded all patients with important protocol violations and was performed for the efficacy endpoints. The PP population excluded patients due to important deviations from the protocol that may have substantially affected the results of the primary endpoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tafluprost | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 2 - 1000 (n=293; n=305) | -6.8 mmHg |
| Tafluprost | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 6 - 1600 (n=295; n=310) | -6.3 mmHg |
| Tafluprost | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 6 - 0800 (n=294; n=308) | -7.3 mmHg |
| Tafluprost | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 12 - 0800 (n=296; n=308) | -7.4 mmHg |
| Tafluprost | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 2 - 1600 (n=289; n=302) | -6.2 mmHg |
| Tafluprost | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 12 - 1000 (n=298; n=312) | -7.0 mmHg |
| Tafluprost | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 6 - 1000 (n=298; n=312) | -7.0 mmHg |
| Tafluprost | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 12 - 1600 (n=295; n=310) | -6.2 mmHg |
| Tafluprost | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 2 - 0800 (n=280; n=295) | -7.1 mmHg |
| Timolol Maleate | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 12 - 1600 (n=295; n=310) | -5.7 mmHg |
| Timolol Maleate | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 2 - 0800 (n=280; n=295) | -6.8 mmHg |
| Timolol Maleate | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 2 - 1000 (n=293; n=305) | -6.1 mmHg |
| Timolol Maleate | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 2 - 1600 (n=289; n=302) | -5.3 mmHg |
| Timolol Maleate | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 6 - 0800 (n=294; n=308) | -7.4 mmHg |
| Timolol Maleate | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 6 - 1000 (n=298; n=312) | -6.6 mmHg |
| Timolol Maleate | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 6 - 1600 (n=295; n=310) | -5.5 mmHg |
| Timolol Maleate | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 12 - 0800 (n=296; n=308) | -7.5 mmHg |
| Timolol Maleate | Mean Intraocular Pressure (IOP) Change From Baseline at All 9 Time Points During the Study (0800, 1000 and 1600 Hrs at Weeks 2, 6, and 12) | Week 12 - 1000 (n=298; n=312) | -6.6 mmHg |
Other Pre-specified
Baseline IOP
IOP was measured using a Goldmann applanation tonometer. The primary evaluation was based on the study eye (the worse eye based on the 0800 hour IOP baseline or the right eye when both eyes had the same IOP).
Time frame: Baseline
Population: The Per-Protocol (PP) approach excluded all patients with important protocol violations and was performed for the efficacy endpoints. The PP population excluded patients due to important deviations from the protocol that may have substantially affected the results of the primary endpoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tafluprost | Baseline IOP | Baseline 0800 timepoint (n=299; n=313) | 26.1 mmHg |
| Tafluprost | Baseline IOP | Baseline 1000 timepoint (n=299; n=313) | 24.8 mmHg |
| Tafluprost | Baseline IOP | Baseline 1600 timepoint (n=296; n=312) | 23.8 mmHg |
| Timolol Maleate | Baseline IOP | Baseline 0800 timepoint (n=299; n=313) | 26.0 mmHg |
| Timolol Maleate | Baseline IOP | Baseline 1000 timepoint (n=299; n=313) | 24.6 mmHg |
| Timolol Maleate | Baseline IOP | Baseline 1600 timepoint (n=296; n=312) | 23.5 mmHg |