Ocular Hypertension, Open-Angle Glaucoma
Conditions
Keywords
Open-angle glaucoma (OAG), Ocular hypertension (OHT), AZORGA®, COSOPT®
Brief summary
The purpose of this study is to evaluate AZORGA® Ophthalmic Suspension compared to COSOPT® Ophthalmic Solution for IOP-lowering efficacy in subjects with open-angle glaucoma or ocular hypertension.
Detailed description
After the screening examination, subjects were enrolled in the study and moved into the observation period. During the observation period, prostaglandin-analog (PGA) monotherapy was applied. After the observation period of 4 weeks or more, the baseline examination was performed. Subjects were then randomized and moved into the treatment period.
Interventions
DRUGBrinzolamide 1%/Timolol maleate 0.5% fixed combination ophthalmic suspension
DRUGDorzolamide hydrochloride 1%/Timolol maleate 0.5% ophthalmic solution
DRUGSubject's habitual PGA monotherapy
Sponsors
Alcon, a Novartis Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Understand the nature of the study and sign informed consent. * Diagnosis of open angle glaucoma or ocular hypertension. * Currently on PGA monotherapy or PGA + alpha-1/beta blocker or PGA + alpha-2 agonist at screening visit, and allowed to instill only PGA for 4 weeks until the baseline visit. * Intraocular pressure (IOP) ≥ 15 mmHg (at least one same eye) at the baseline visit. * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* History of bronchial asthma, bronchospasm, or serious chronic obstruction pulmonary disease. * Uncontrolled heart failure, sinus bradycardia, A-V block (II, III grade), cardiogenic shock, right heart failure due to pulmonary hypertension or congestive heart failure. * History of hypersensitivity to any of the excipients of the study medications. * Severe renal function disorders, diabetic ketoacidosis and metabolic acidosis, uncontrolled diabetes, or hepatic disorders. * Corneal disorder or history of chronic, recurrent or current severe inflammatory eye disease in either eye. * History of ocular trauma in either eye within 6 months prior to the screening examination. * Ocular infection or ocular inflammation in either eye. * History of or current clinically significant or progressive retinal disease in either eye. * Intraocular surgery in either eye within 6 months prior to the screening examination. * Ocular laser surgery in either eye within 3 months prior to the screening examination. * Any abnormality preventing reliable applanation tonometry of either eye. * Best-corrected visual acuity (BCVA) worse than 0.2 score (decimal visual acuity) in either eye. * Severe visual field loss in either eye. * Use of prohibited medication, as specified in the protocol. * Pregnant, lactating, or intending to become pregnant during the study period. * Currently on therapy or have been on therapy with another investigational agent within 30 days prior to the screening examination. * History of or current evidence of a severe illness or any other condition which would make the subject, in the opinion of the investigator, unsuitable for the study. * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline in Intraocular Pressure (IOP) at 11 AM | Baseline (Day 0), Week 4, Week 8 at 11 AM | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). Data from 4 and 8 weeks at 11 AM were pooled, and a negative change indicates an improvement. One eye (target eye) was used for the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline in IOP at 9 AM | Baseline (Day 0), Week 4, Week 8 at 9 AM | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). Data from 4 and 8 weeks at 9 AM were pooled, and a negative change indicates an improvement. One eye (target eye) was used for the analysis. |
Countries
Japan
Participant flow
Recruitment details
Subjects were recruited from 26 study sites in Japan.
Pre-assignment details
Of the 218 enrolled, 6 subjects withdrew informed consent and 11 were exited as screen failures prior to randomization. This reporting group includes all randomized subjects (201).
Participants by arm
| Arm | Count |
|---|---|
| BRI/TIM Brinzolamide 1%/Timolol maleate 0.5% fixed combination ophthalmic suspension, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks. | 98 |
| DOR/TIM Dorzolamide hydrochloride 1%/Timolol maleate 0.5% ophthalmic solution, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks. | 101 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | BRI/TIM | DOR/TIM |
|---|---|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 12 | 63.1 years STANDARD_DEVIATION 11.8 | 64.4 years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 105 Participants | 52 Participants | 53 Participants |
| Sex: Female, Male Male | 94 Participants | 46 Participants | 48 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 | 0 / 218 | 21 / 98 | 16 / 103 |
| serious Total, serious adverse events | 1 / 218 | 1 / 98 | 0 / 103 |
Outcome results
Primary
Least Squares Mean Change From Baseline in Intraocular Pressure (IOP) at 11 AM
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). Data from 4 and 8 weeks at 11 AM were pooled, and a negative change indicates an improvement. One eye (target eye) was used for the analysis.
Time frame: Baseline (Day 0), Week 4, Week 8 at 11 AM
Population: This analysis population includes all subjects who received study medication and met inclusion/exclusion criteria prior to randomization (Per Protocol Set).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| BRI/TIM | Least Squares Mean Change From Baseline in Intraocular Pressure (IOP) at 11 AM | Baseline | 17.0 mmHg |
| BRI/TIM | Least Squares Mean Change From Baseline in Intraocular Pressure (IOP) at 11 AM | Mean change pooled over Week 4 and Week 8 | -3.3 mmHg |
| DOR/TIM | Least Squares Mean Change From Baseline in Intraocular Pressure (IOP) at 11 AM | Baseline | 17.0 mmHg |
| DOR/TIM | Least Squares Mean Change From Baseline in Intraocular Pressure (IOP) at 11 AM | Mean change pooled over Week 4 and Week 8 | -3.4 mmHg |
Secondary
Least Squares Mean Change From Baseline in IOP at 9 AM
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). Data from 4 and 8 weeks at 9 AM were pooled, and a negative change indicates an improvement. One eye (target eye) was used for the analysis.
Time frame: Baseline (Day 0), Week 4, Week 8 at 9 AM
Population: Per Protocol Set (PPS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| BRI/TIM | Least Squares Mean Change From Baseline in IOP at 9 AM | Baseline | 17.4 mmHg |
| BRI/TIM | Least Squares Mean Change From Baseline in IOP at 9 AM | Change at Pool (Week 4, Week 8) | -3.3 mmHg |
| DOR/TIM | Least Squares Mean Change From Baseline in IOP at 9 AM | Baseline | 17.3 mmHg |
| DOR/TIM | Least Squares Mean Change From Baseline in IOP at 9 AM | Change at Pool (Week 4, Week 8) | -2.9 mmHg |