Effect of SIMBRINZA® Suspension as an Added Therapy to a Prostaglandin Analogue
Study Details
Study Description
Brief Summary
The purpose of this study is to demonstrate the additive effect of brinzolamide 1%/brimonidine 0.2% (SIMBRINZA® suspension) in subjects with either open angle glaucoma or ocular hypertension who are currently on a prostaglandin analogue (PGA) monotherapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
This study was divided into 2 sequential phases. The Screening/Eligibility Phase included one Screening Visit and two Eligibility Visits, during which subjects washed out of all other intraocular pressure (IOP)-lowering medications and dosed with TRAVATAN Z®, XALATAN®, or LUMIGAN®, 1 drop instilled in each eye once daily for 28 days. Subjects who met all inclusion/exclusion criteria were randomized at the second Eligibility Visit. The Treatment Phase consisted of two on-therapy visits (Week 2 and Week 6).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SIMBRINZA Brinzolamide 1%/brimonidine 0.2% ophthalmic suspension, 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks |
Drug: Brinzolamide 1%/brimonidine 0.2% ophthalmic suspension
Other Names:
Drug: Prostaglandin analogue
Other Names:
|
| Placebo Comparator: Vehicle Inactive ingredients, 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks |
Drug: Vehicle
Inactive ingredients used as a placebo comparator
Drug: Prostaglandin analogue
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mean Diurnal Intraocular Pressure (IOP) at Week 6 [Week 6]
Diurnal IOP was defined as the average of the four timepoints measured (8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Secondary Outcome Measures
- Mean Diurnal IOP Change From Baseline to Week 6 [Baseline, Week 6]
Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP change was defined as the average of the four changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP.
- Mean Diurnal IOP Percentage Change From Baseline to Week 6 [Baseline, Week 6]
Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP Percentage Change was defined as the average of the four percent changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A more negative percent change from baseline indicates a greater amount of improvement, i.e., a reduction of IOP.
- Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) [Week 6]
IOP was assessed using Goldmann applanation tonometry and reported in mmHg. One eye was chosen as the study eye and only data for the study eye were used for the analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of open angle glaucoma (including open-angle glaucoma with pseudoexfoliation or pigment dispersion) or ocular hypertension;
-
Mean intraocular pressure (IOP) measurements in at least 1 eye (study eye) of ≥ 21 mmHg and <32 mmHg at 2 consecutive visits (Eligibility 1 and Eligibility 2);
-
Previously prescribed TRAVATAN Z® 0.004%, XALATAN® 0.005%, or LUMIGAN® 0.01% monotherapy for at least 28 days prior to the Screening Visit;
-
Able to understand and sign Informed Consent Document;
-
Other protocol-defined inclusion criteria may apply.
Exclusion Criteria:
-
Women of childbearing potential who are pregnant, breastfeeding, or do not agree to use an adequate birth control method throughout the study;
-
Any form of glaucoma other than open angle glaucoma or ocular hypertension;
-
Severe central visual field loss;
-
Chronic, recurrent, or severe inflammatory eye disease;
-
Ocular trauma within the past 6 months;
-
Ocular infection or ocular inflammation within the past 3 months;
-
Best-corrected visual acuity score worse than approximately 20/80 Snellen;
-
Eye surgery within the past 6 months;
-
Any condition, including severe illness, which would make the subject unsuitable for the study in the opinion of the Investigator;
-
Use of any additional topical or systemic ocular hypertensive medication during the study;
-
Patients who, in the opinion of the Investigator, cannot discontinue all IOP-lowering ocular medication(s) per the appropriate washout schedule prior to Eligibility 1 Visit;
-
Other protocol-defined exclusion criteria may apply.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Alcon Research
Investigators
- Study Director: Steve Burmaster, PhD, Alcon Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- M-13-020
Study Results
Participant Flow
| Recruitment Details | Participants were recruited and enrolled from 30 investigative sites located in the US. |
|---|---|
| Pre-assignment Detail | Of the 282 enrolled, 93 participants were exited from the study as screen failures prior to randomization. This reporting group includes all randomized participants (189). Note: One subject randomized to SIMBRINZA® Suspension was not exposed to investigational product. |
| Arm/Group Title | SIMBRINZA | Vehicle |
|---|---|---|
| Arm/Group Description | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks |
| Period Title: Overall Study | ||
| STARTED | 94 | 95 |
| Treated | 93 | 95 |
| COMPLETED | 83 | 92 |
| NOT COMPLETED | 11 | 3 |
Baseline Characteristics
| Arm/Group Title | SIMBRINZA | Vehicle | Total |
|---|---|---|---|
| Arm/Group Description | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | Total of all reporting groups |
| Overall Participants | 88 | 94 | 182 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
65.5
(9.4)
|
64.7
(9.6)
|
65.1
(9.5)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
53
60.2%
|
63
67%
|
116
63.7%
|
| Male |
35
39.8%
|
31
33%
|
66
36.3%
|
| Mean Diurnal Intraocular Pressure (IOP) at Baseline (mmHg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mmHg] |
22.68
(2.123)
|
22.39
(2.774)
|
22.53
(2.478)
|
Outcome Measures
| Title | Mean Diurnal Intraocular Pressure (IOP) at Week 6 |
|---|---|
| Description | Diurnal IOP was defined as the average of the four timepoints measured (8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). |
| Time Frame | Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy visit (intent-to-treat). Last observation carried forward (LOCF) was not utilized; therefore, results report subjects present at Week 6 with no imputation for missingness. |
| Arm/Group Title | SIMBRINZA | Vehicle |
|---|---|---|
| Arm/Group Description | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks |
| Measure Participants | 83 | 92 |
| Mean (Standard Deviation) [mmHg] |
17.01
(2.897)
|
20.37
(3.914)
|
| Title | Mean Diurnal IOP Change From Baseline to Week 6 |
|---|---|
| Description | Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP change was defined as the average of the four changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. |
| Time Frame | Baseline, Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy visit (intent-to-treat). Last observation carried forward (LOCF) was not utilized; therefore, results report subjects present at Week 6 with no imputation for missingness. |
| Arm/Group Title | SIMBRINZA | Vehicle |
|---|---|---|
| Arm/Group Description | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks |
| Measure Participants | 83 | 92 |
| Mean (Standard Deviation) [mmHg] |
-5.69
(2.571)
|
-1.99
(2.865)
|
| Title | Mean Diurnal IOP Percentage Change From Baseline to Week 6 |
|---|---|
| Description | Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP Percentage Change was defined as the average of the four percent changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A more negative percent change from baseline indicates a greater amount of improvement, i.e., a reduction of IOP. |
| Time Frame | Baseline, Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy visit (intent-to-treat). Last observation carried forward (LOCF) was not utilized; therefore, results report subjects present at Week 6 with no imputation for missingness. |
| Arm/Group Title | SIMBRINZA | Vehicle |
|---|---|---|
| Arm/Group Description | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks |
| Measure Participants | 83 | 92 |
| Mean (Standard Deviation) [percent change] |
-24.88
(10.818)
|
-8.50
(12.396)
|
| Title | Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) |
|---|---|
| Description | IOP was assessed using Goldmann applanation tonometry and reported in mmHg. One eye was chosen as the study eye and only data for the study eye were used for the analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). |
| Time Frame | Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy visit (intent-to-treat). Last observation carried forward (LOCF) was not utilized; therefore, results report subjects present at Week 6 with no imputation for missingness. |
| Arm/Group Title | SIMBRINZA | Vehicle |
|---|---|---|
| Arm/Group Description | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks |
| Measure Participants | 83 | 92 |
| 8 AM |
19.4
(3.53)
|
21.4
(4.33)
|
| 10 AM |
15.8
(3.54)
|
20.2
(4.17)
|
| 3 PM |
17.2
(3.15)
|
19.9
(4.28)
|
| 5 PM |
15.6
(3.14)
|
19.9
(4.41)
|
Adverse Events
| Time Frame | Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol. | |||||
| Arm/Group Title | Pre-Treatment | SIMBRINZA | Vehicle | |||
| Arm/Group Description | Prostaglandin analogue, 1 drop in each eye at bedtime for a 4-week run-in period | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | |||
All Cause Mortality |
||||||
| Pre-Treatment | SIMBRINZA | Vehicle | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Pre-Treatment | SIMBRINZA | Vehicle | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/282 (0%) | 1/93 (1.1%) | 0/95 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypoglycaemia | 0/282 (0%) | 1/93 (1.1%) | 0/95 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Metastatic malignant melanoma | 0/282 (0%) | 1/93 (1.1%) | 0/95 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Pre-Treatment | SIMBRINZA | Vehicle | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/282 (0.7%) | 16/93 (17.2%) | 8/95 (8.4%) | |||
| Eye disorders | ||||||
| Vision Blurred | 0/282 (0%) | 9/93 (9.7%) | 6/95 (6.3%) | |||
| Eye irritation | 1/282 (0.4%) | 6/93 (6.5%) | 1/95 (1.1%) | |||
| Eye Pruritus | 0/282 (0%) | 6/93 (6.5%) | 0/95 (0%) | |||
| Ocular hyperaemia | 2/282 (0.7%) | 5/93 (5.4%) | 2/95 (2.1%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
Results Point of Contact
| Name/Title | Global Brand Leader, Medical Affairs, Glaucoma |
|---|---|
| Organization | Alcon Research, Ltd. |
| Phone | 1-888-451-3937 |
| alcon.medinfo@alcon.com |
- M-13-020