Glaucoma
Conditions
Brief summary
The clinical study compares safety and efficacy of MK0507A (dorzolamide 1.0% / timolol 0.5%) with 1) timolol 0.5% and with 2) concomitant therapy with dorzolamide 1.0% / timolol 0.5% in patients with glaucoma and ocular hypertension.
Interventions
Dorzolamide hydrochloride 1% + timolol 0.5%, 8-week
timolol maleate 0.5%, 8-week
DRUGComparator: dorzolamide hydrochloride
dorzolamide hydrochloride 1%, 8-week
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with glaucoma and ocular hypertension
Exclusion criteria
* History of ocular surgery within 3 months * Administration contradiction to timolol and dorzolamide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks | 8 weeks | Change from baseline to 8 weeks in Intraocular Pressure (IOP) assessed 2 hours after ocular instillation (at Hour 2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Outflow Pressure Reduction Rate at 8 Weeks | 8 weeks | Percent Change from baseline to 8 weeks in Outflow Pressure Reduction Rate assessed 2 hours after ocular instillation (at Hour 2) |
| Percent Change From Baseline in Intraocular Pressure (IOP) at 8 Weeks | 8 Weeks | Percent Change from baseline to 8 weeks in Intraocular Pressure (IOP) assessed 2 hours after ocular instillation (at Hour 2) |
Participant flow
Recruitment details
Phase III. Studied period: April 9, 2007 (date study therapy started for the first subject) to February 16, 2008 (the last subject's last visit stipulated in study protocol). Study was conducted at 67 clinical sites.
Pre-assignment details
Outpatients with primary open angle glaucoma (broad definition) and/or ocular hypertension received 4-week timolol 0.5% monotherapy in the wash-out period before the study randomization.
Participants by arm
| Arm | Count |
|---|---|
| MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination) MK0507A (Dorzolamide 1.0% / Timolol 0.5% combination), one drop per dose twice daily to the study eye. | 189 |
| Timolol 0.5% Timolol 0.5%, one drop per dose twice daily to the study eye. | 92 |
| Concomitant (Dorzolamide 1.0% / Timolol 0.5%) Concomitant (Dorzolamide 1.0%, one drop per dose three times daily to the study eye / Timolol 0.5%, one drop per dose twice daily to the study eye). | 193 |
| Total | 474 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 1 | 6 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination) | Timolol 0.5% | Concomitant (Dorzolamide 1.0% / Timolol 0.5%) | Total |
|---|---|---|---|---|
| Age, Continuous | 63.2 Years STANDARD_DEVIATION 10.8 | 61.3 Years STANDARD_DEVIATION 11.6 | 62.3 Years STANDARD_DEVIATION 12.7 | 62.4 Years STANDARD_DEVIATION 11.7 |
| Age, Customized <65 years | 92 participants | 50 participants | 102 participants | 244 participants |
| Age, Customized >=65 years | 97 participants | 42 participants | 91 participants | 230 participants |
| Diagnosis Normal-tension glaucoma | 8 participants | 6 participants | 4 participants | 18 participants |
| Diagnosis Ocular hypertension | 74 participants | 35 participants | 99 participants | 208 participants |
| Diagnosis Open-angle glaucoma | 107 participants | 51 participants | 90 participants | 248 participants |
| Intraocular pressure (IOP) at Hour 2 | 20.54 mmHg STANDARD_DEVIATION 2.07 | 20.23 mmHg STANDARD_DEVIATION 1.85 | 20.38 mmHg STANDARD_DEVIATION 2.31 | 20.42 mmHg STANDARD_DEVIATION 2.13 |
| Sex: Female, Male Female | 104 Participants | 43 Participants | 98 Participants | 245 Participants |
| Sex: Female, Male Male | 85 Participants | 49 Participants | 95 Participants | 229 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 36 / — | 12 / — | 40 / — |
| serious Total, serious adverse events | 2 / — | 1 / — | 0 / — |
Outcome results
Primary
Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks
Change from baseline to 8 weeks in Intraocular Pressure (IOP) assessed 2 hours after ocular instillation (at Hour 2)
Time frame: 8 weeks
Population: Last observed value during the 8-week treatment period was used in the Full Analysis Set (FAS).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination) | Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks | -2.50 mmHg |
| Timolol 0.5% | Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks | -1.82 mmHg |
| Concomitant (Dorzolamide 1.0% / Timolol 0.5%) | Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks | -2.78 mmHg |
95% CI: [-1.3, -0.06]
95% CI: [-0.22, 0.78]
Secondary
Percent Change From Baseline in Intraocular Pressure (IOP) at 8 Weeks
Percent Change from baseline to 8 weeks in Intraocular Pressure (IOP) assessed 2 hours after ocular instillation (at Hour 2)
Time frame: 8 Weeks
Population: Last observed value during the 8-week treatment period was used in the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination) | Percent Change From Baseline in Intraocular Pressure (IOP) at 8 Weeks | -11.99 Percent Change |
| Timolol 0.5% | Percent Change From Baseline in Intraocular Pressure (IOP) at 8 Weeks | -8.74 Percent Change |
| Concomitant (Dorzolamide 1.0% / Timolol 0.5%) | Percent Change From Baseline in Intraocular Pressure (IOP) at 8 Weeks | -13.46 Percent Change |
Secondary
Percent Change From Baseline in Outflow Pressure Reduction Rate at 8 Weeks
Percent Change from baseline to 8 weeks in Outflow Pressure Reduction Rate assessed 2 hours after ocular instillation (at Hour 2)
Time frame: 8 weeks
Population: Last observed value during the 8-week treatment period was used in the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination) | Percent Change From Baseline in Outflow Pressure Reduction Rate at 8 Weeks | 23.47 Percent Change |
| Timolol 0.5% | Percent Change From Baseline in Outflow Pressure Reduction Rate at 8 Weeks | 17.17 Percent Change |
| Concomitant (Dorzolamide 1.0% / Timolol 0.5%) | Percent Change From Baseline in Outflow Pressure Reduction Rate at 8 Weeks | 26.75 Percent Change |