Glaucoma, Ocular Hypertension
Conditions
Keywords
Glaucoma, Ocular, Hypertension, OAG, POAG, OHT
Brief summary
The purpose of this study is to evaluate Travoprost/Brinzolamide fixed combination (Trav/Brinz) administered twice daily as compared to each of its marketed components (TRAVATAN Z® solution and AZOPT® suspension) and to the unfixed combination of TRAVATAN Z® plus AZOPT® in lowering intraocular pressure (IOP).
Detailed description
This study was divided into two phases conducted in sequence. Phase I was the Screening/Eligibility Phase, which included a Screening Visit, followed by two Eligibility Visits. Phase II was the randomized, double-masked, 6-week Treatment Phase which included on-therapy visits at Week 2 and Week 6. Travoprost was administered in 1 of 3 concentration levels (A-C), where A=lowest and C=highest.
Interventions
DRUGDose Level B / Brinzolamide 1% ophthalmic suspension
Fixed combination
DRUGDose Level C / Brinzolamide 1% ophthalmic suspension
Fixed combination
DRUGDose Level A / Brinzolamide 1% ophthalmic suspension
Fixed combination
DRUGBrinzolamide 1% ophthalmic suspension AZOPT®
DRUGTravoprost 0.004% ophthalmic solution TRAVATAN Z®
DRUGTravoprost solution vehicle
Inactive ingredients used for masking purposes
DRUGBrinzolamide suspension vehicle
Inactive ingredients used for masking purposes
Sponsors
Alcon Research
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
* Diagnosed with open-angle glaucoma (including open-angle glaucoma with pseudoexfoliation or pigment dispersion) or ocular hypertension; * IOP within the protocol-specified range at both the Eligibility 1 and 2 Visits. Mean IOP must not be \>36 mmHg at any time point; * Able to understand and sign an informed consent form; * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Woman of childbearing potential who is currently pregnant, intends to become pregnant during the study period, breastfeeding, or not using adequate birth control methods to prevent pregnancy throughout the study; * Unable to discontinue all IOP-lowering ocular medication(s) per the appropriate washout schedule prior to the E1 Visit; * Chronic, recurrent or severe inflammatory eye disease; * Ocular trauma within the past 6 months prior to the Screening Visit; * Ocular infection or ocular inflammation within the past 3 months prior to the Screening Visit; * Clinically relevant or progressive retinal disease such as retinal degeneration, diabetic retinopathy, or retinal detachment; * Best-corrected visual acuity (BCVA) score worse than 55 ETDRS letters (equivalent to approximately 0.60 logMAR, 20/80 Snellen, or 0.25 decimal); * Other ocular pathology (including severe dry eye) that may, in the opinion of the Investigator, preclude the administration of a topical prostaglandin analogue or topical carbonic anhydrase inhibitor; * Intraocular surgery within the past 6 months prior to the Screening Visit; * Ocular laser surgery within the past 3 months prior to the Screening Visit; * Any abnormality preventing reliable applanation tonometry; * Any other conditions including severe illness which would make the subject, in the opinion of the Investigator, unsuitable for the study; * History of hepatic or renal disease that would preclude the safe administration of a carbonic anhydrase inhibitor (CAI) in the opinion of the Investigator; * Hypersensitivity to prostaglandin analogues, topical or oral CAIs, sulfonamide derivatives, or to any component of the study medications in the opinion of the Investigator; * Recent (within 4 weeks of the Eligibility 1 Visit) use of high dose (\> 1 g daily) salicylate therapy; * Use of any additional topical or systemic ocular hypotensive medication during the study; * Concurrent use of glucocorticoids administered by any route; * Less than 30 days stable dosing regimen before the Screening Visit of any medications (excluding the IOP-lowering treatments) or substances administered by any route and used on a chronic basis that may affect IOP (ie, β adrenergic blocking agents); * Therapy with another investigational agent within 30 days prior to the Screening Visit; * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean IOP at Week 6 | Week 6, 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) was used for the analysis. |
Participant flow
Recruitment details
Subjects were recruited from 19 study centers located in the US.
Pre-assignment details
Of the 327 enrolled, 61 subjects were discontinued prior to randomization. This reporting group includes all randomized subjects (266).
Participants by arm
| Arm | Count |
|---|---|
| TravA/Brinz Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks | 44 |
| TravB/Brinz Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks | 44 |
| TravC/Brinz Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks | 44 |
| TRAV Z Suspension vehicle, 1 drop twice daily in the treated eye(s) morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks | 45 |
| AZOPT Ophthalmic suspension, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night for 6 weeks | 45 |
| TRAV Z + AZOPT Ophthalmic suspension, 1 drop twice daily in the treated eye(s) twice daily morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks | 43 |
| Total | 265 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | TravA/Brinz | TravB/Brinz | TravC/Brinz | TRAV Z | AZOPT | TRAV Z + AZOPT | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.4 years STANDARD_DEVIATION 10.7 | 66.2 years STANDARD_DEVIATION 10.4 | 64.4 years STANDARD_DEVIATION 11.2 | 64.2 years STANDARD_DEVIATION 10.4 | 63.1 years STANDARD_DEVIATION 8.4 | 65.3 years STANDARD_DEVIATION 10.6 | 64.8 years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 29 Participants | 26 Participants | 30 Participants | 25 Participants | 23 Participants | 19 Participants | 152 Participants |
| Sex: Female, Male Male | 15 Participants | 18 Participants | 14 Participants | 20 Participants | 22 Participants | 24 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 44 | 11 / 44 | 15 / 44 | 10 / 45 | 9 / 45 | 13 / 44 | 1 / 327 |
| serious Total, serious adverse events | 0 / 44 | 0 / 44 | 0 / 44 | 1 / 45 | 0 / 45 | 0 / 44 | 1 / 327 |
Outcome results
Primary
Mean IOP at Week 6
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) was used for the analysis.
Time frame: Week 6, 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM
Population: This analysis population includes all subjects who were randomized, received study medication, and completed at least 1 scheduled on-therapy study visit, based upon a last on-therapy carried forward (LOCF) analysis. Here, n is the number of subjects with non-missing values at the specific time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TravA/Brinz | Mean IOP at Week 6 | 8 PM, n=44, 44, 44, 43, 45, 43 | 18.4 mmHg | Standard Error 0.43 |
| TravA/Brinz | Mean IOP at Week 6 | 10 AM | 18.9 mmHg | Standard Error 0.47 |
| TravA/Brinz | Mean IOP at Week 6 | 4PM | 18.5 mmHg | Standard Error 0.46 |
| TravA/Brinz | Mean IOP at Week 6 | 8 AM | 20.2 mmHg | Standard Error 0.52 |
| TravA/Brinz | Mean IOP at Week 6 | 12 PM | 18.9 mmHg | Standard Error 0.47 |
| TravB/Brinz | Mean IOP at Week 6 | 8 AM | 18.7 mmHg | Standard Error 0.48 |
| TravB/Brinz | Mean IOP at Week 6 | 4PM | 17.5 mmHg | Standard Error 0.43 |
| TravB/Brinz | Mean IOP at Week 6 | 12 PM | 17.3 mmHg | Standard Error 0.5 |
| TravB/Brinz | Mean IOP at Week 6 | 10 AM | 17.2 mmHg | Standard Error 0.35 |
| TravB/Brinz | Mean IOP at Week 6 | 8 PM, n=44, 44, 44, 43, 45, 43 | 17.5 mmHg | Standard Error 0.39 |
| TravC/Brinz | Mean IOP at Week 6 | 4PM | 17.3 mmHg | Standard Error 0.46 |
| TravC/Brinz | Mean IOP at Week 6 | 12 PM | 17.7 mmHg | Standard Error 0.51 |
| TravC/Brinz | Mean IOP at Week 6 | 8 AM | 19.9 mmHg | Standard Error 0.58 |
| TravC/Brinz | Mean IOP at Week 6 | 10 AM | 18.2 mmHg | Standard Error 0.55 |
| TravC/Brinz | Mean IOP at Week 6 | 8 PM, n=44, 44, 44, 43, 45, 43 | 17.2 mmHg | Standard Error 0.4 |
| TRAV Z | Mean IOP at Week 6 | 8 AM | 19.3 mmHg | Standard Error 0.48 |
| TRAV Z | Mean IOP at Week 6 | 10 AM | 17.4 mmHg | Standard Error 0.47 |
| TRAV Z | Mean IOP at Week 6 | 12 PM | 17.2 mmHg | Standard Error 0.5 |
| TRAV Z | Mean IOP at Week 6 | 4PM | 17.6 mmHg | Standard Error 0.44 |
| TRAV Z | Mean IOP at Week 6 | 8 PM, n=44, 44, 44, 43, 45, 43 | 17.3 mmHg | Standard Error 0.43 |
| AZOPT | Mean IOP at Week 6 | 12 PM | 19.5 mmHg | Standard Error 0.53 |
| AZOPT | Mean IOP at Week 6 | 8 AM | 22.0 mmHg | Standard Error 0.45 |
| AZOPT | Mean IOP at Week 6 | 8 PM, n=44, 44, 44, 43, 45, 43 | 19.3 mmHg | Standard Error 0.48 |
| AZOPT | Mean IOP at Week 6 | 4PM | 19.1 mmHg | Standard Error 0.5 |
| AZOPT | Mean IOP at Week 6 | 10 AM | 19.7 mmHg | Standard Error 0.5 |
| TRAV Z + AZOPT | Mean IOP at Week 6 | 8 PM, n=44, 44, 44, 43, 45, 43 | 18.1 mmHg | Standard Error 0.49 |
| TRAV Z + AZOPT | Mean IOP at Week 6 | 12 PM | 18.0 mmHg | Standard Error 0.57 |
| TRAV Z + AZOPT | Mean IOP at Week 6 | 10 AM | 18.2 mmHg | Standard Error 0.59 |
| TRAV Z + AZOPT | Mean IOP at Week 6 | 4PM | 18.0 mmHg | Standard Error 0.52 |
| TRAV Z + AZOPT | Mean IOP at Week 6 | 8 AM | 20.3 mmHg | Standard Error 0.72 |