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SIMBRINZA® Suspension BID as an Adjunctive to Prostaglandin Analogue (PGA)

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ClinicalTrials.gov Identifier: NCT02419508
Recruitment Status : Completed
First Posted : April 17, 2015
Results First Posted : November 15, 2018
Last Update Posted : November 15, 2018
Sponsor:
Information provided by (Responsible Party):
Alcon Research

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Open-Angle Glaucoma
Ocular Hypertension
Interventions Drug: Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension
Drug: Brinz/brim vehicle
Drug: Prostaglandin analogue
Enrollment 290
Recruitment Details This study was conducted at 37 sites located in Argentina (3), Australia (4), Canada (12), Chile (3), France (1), Germany (3), Greece (2), Israel (3), Spain (3), and United Kingdom (3).
Pre-assignment Details Of the 290 subjects enrolled in the study, 102 were exited during the Screening/Eligibility period. This reporting group includes all randomized subjects. One randomized subject did not receive investigational product and is excluded from the Full Analysis Set and the Safety Analysis Set.
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA
Hide Arm/Group Description Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Period Title: Overall Study
Started 96 92
Full Analysis Set 95 92
Safety Analysis Set 95 92
Completed 86 88
Not Completed 10 4
Reason Not Completed
Adverse Event             9             3
Withdrawal by Subject             1             0
Other - Reason not specified             0             1
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA Total
Hide Arm/Group Description Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days Total of all reporting groups
Overall Number of Baseline Participants 95 92 187
Hide Baseline Analysis Population Description
This analysis population includes all randomized subjects who received a dose of study medication and had at least 1 of the 2 scheduled on-treatment visits [Full Analysis Set (FAS)].
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 95 participants 92 participants 187 participants
66.5  (10.70) 67.9  (11.65) 67.2  (11.17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 92 participants 187 participants
Female
55
  57.9%
43
  46.7%
98
  52.4%
Male
40
  42.1%
49
  53.3%
89
  47.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 92 participants 187 participants
Hispanic or Latino
23
  24.2%
29
  31.5%
52
  27.8%
Not Hispanic or Latino
72
  75.8%
62
  67.4%
134
  71.7%
Unknown or Not Reported
0
   0.0%
1
   1.1%
1
   0.5%
Baseline Diurnal IOP   [1] 
Mean (Standard Deviation)
Unit of measure:  Millimeters mercury (mmHg)
Number Analyzed 95 participants 92 participants 187 participants
22.8  (2.39) 22.9  (2.32) 22.8  (2.35)
[1]
Measure Description: IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 92 participants 187 participants
Europe, Australia
45
  47.4%
44
  47.8%
89
  47.6%
Latin America, Canada
50
  52.6%
48
  52.2%
98
  52.4%
1.Primary Outcome
Title Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6
Hide Description IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Overall Number of Participants Analyzed 86 88
Mean (Standard Deviation)
Unit of Measure: mmHg
-5.6  (2.72) -2.1  (2.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SIMBRINZA + PGA, Vehicle + PGA
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
2.Secondary Outcome
Title Mean Diurnal IOP at Week 6
Hide Description IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with data available
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Overall Number of Participants Analyzed 86 88
Mean (Standard Deviation)
Unit of Measure: mmHg
17.2  (3.49) 20.9  (3.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SIMBRINZA + PGA, Vehicle + PGA
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
3.Secondary Outcome
Title Mean Percentage Change From Baseline in Diurnal IOP at Week 6
Hide Description IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Overall Number of Participants Analyzed 86 88
Mean (Standard Deviation)
Unit of Measure: percent change
-24.7  (12.17) -9.5  (10.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SIMBRINZA + PGA, Vehicle + PGA
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline in IOP at 11:00 at Week 6
Hide Description IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Overall Number of Participants Analyzed 95 92
Mean (Standard Deviation)
Unit of Measure: mmHg
Baseline Number Analyzed 95 participants 92 participants
22.4  (2.70) 22.6  (2.69)
Change from baseline Number Analyzed 86 participants 88 participants
-7.0  (3.19) -2.4  (2.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SIMBRINZA + PGA, Vehicle + PGA
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
5.Secondary Outcome
Title Mean Percentage Change From Baseline in IOP at 11:00 at Week 6
Hide Description IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Overall Number of Participants Analyzed 86 88
Mean (Standard Deviation)
Unit of Measure: percent change
-31.3  (14.81) -10.8  (11.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SIMBRINZA + PGA, Vehicle + PGA
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
6.Secondary Outcome
Title Mean Change From Baseline in IOP at 09:00 at Week 6
Hide Description IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 09:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Overall Number of Participants Analyzed 95 92
Mean (Standard Deviation)
Unit of Measure: mmHg
Baseline Number Analyzed 95 participants 92 participants
23.4  (2.40) 23.4  (2.22)
Change from baseline Number Analyzed 86 participants 88 participants
-4.9  (3.06) -2.5  (2.87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SIMBRINZA + PGA, Vehicle + PGA
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
7.Secondary Outcome
Title Mean Percentage Change From Baseline at 09:00 at Week 6
Hide Description IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 9:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits.A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
Overall Number of Participants Analyzed 86 88
Mean (Standard Deviation)
Unit of Measure: percent change
-21.0  (13.36) -10.9  (11.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SIMBRINZA + PGA, Vehicle + PGA
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Time Frame Baseline through study completion, an average of 6 weeks.
Adverse Event Reporting Description Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.This analysis population includes all subjects who received a dose of study medication (Safety Analysis Set).
 
Arm/Group Title SIMBRINZA + PGA Vehicle + PGA
Hide Arm/Group Description Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days
All-Cause Mortality
SIMBRINZA + PGA Vehicle + PGA
Affected / at Risk (%) Affected / at Risk (%)
Total   0/95 (0.00%)      0/92 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
SIMBRINZA + PGA Vehicle + PGA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/95 (1.05%)      0/92 (0.00%)    
Cardiac disorders     
Cardiac failure  1  1/95 (1.05%)  1 0/92 (0.00%)  0
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SIMBRINZA + PGA Vehicle + PGA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/95 (10.53%)      1/92 (1.09%)    
Eye disorders     
Ocular hyperaemia  1  5/95 (5.26%)  9 1/92 (1.09%)  1
Gastrointestinal disorders     
Dry mouth  1  5/95 (5.26%)  5 0/92 (0.00%)  0
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
Results Point of Contact
Name/Title: Brand Medical Director Ophtha, GMA Ophthalmics
Organization: Alcon, A Novartis Division
Phone: 1-888-451-3937
Responsible Party: Alcon Research
ClinicalTrials.gov Identifier: NCT02419508     History of Changes
Other Study ID Numbers: GLH694-P001
2015-000736-15 ( EudraCT Number )
REec-2015-1723 ( Registry Identifier: Registro Espanol de Estudios Clinicos )
First Submitted: April 14, 2015
First Posted: April 17, 2015
Results First Submitted: October 16, 2018
Results First Posted: November 15, 2018
Last Update Posted: November 15, 2018