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Safety and Efficacy of SIMBRINZA® BID as an Adjunctive to DUOTRAV®

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ClinicalTrials.gov Identifier: NCT02730871
Recruitment Status : Terminated (Enrollment Challenges)
First Posted : April 7, 2016
Results First Posted : May 17, 2019
Last Update Posted : May 29, 2019
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 tartrate 0.2% ophthalmic suspension
Drug: Brinzolamide/brimonidine vehicle
Drug: Travoprost 0.004%/timolol 0.5% solution
Enrollment 173
Recruitment Details Subjects were recruited from sites located in Argentina, Australia, Belgium, Chile, Columbia, Germany, Greece, Italy, Malaysia, Poland, Spain, Taiwan, and the United Kingdom.
Pre-assignment Details Of the 173 enrolled, 39 subjects were exited as screen failures prior to randomization. This reporting group includes all randomized subjects (134).
Arm/Group Title Simbrinza + Duotrav Vehicle + Duotrav
Hide Arm/Group Description Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase) Brinzolamide/brimonidine vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Period Title: Overall Study
Started [1] 67 67
Full Analysis Set (FAS) [2] 67 67
Safety Analysis Set [3] 67 67
Completed [4] 61 67
Not Completed 6 0
Reason Not Completed
Adverse Event             6             0
[1]
All randomized subjects
[2]
Randomized subjects with a baseline assessment who completed at least 1 scheduled on-therapy visit
[3]
All subjects who received a dose of masked investigational product
[4]
All subjects who completed the treatment phase whether on study treatment or not
Arm/Group Title Simbrinza + Duotrav Vehicle + Duotrav Total
Hide Arm/Group Description Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase) Brinzolamide/brimonidine vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase) Total of all reporting groups
Overall Number of Baseline Participants 67 67 134
Hide Baseline Analysis Population Description
Full Analysis Set
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 67 participants 67 participants 134 participants
65.7  (13.47) 65.7  (11.77) 65.7  (12.60)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 67 participants 134 participants
Female
32
  47.8%
41
  61.2%
73
  54.5%
Male
35
  52.2%
26
  38.8%
61
  45.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 67 participants 134 participants
White
50
  74.6%
57
  85.1%
107
  79.9%
Black or African American
2
   3.0%
0
   0.0%
2
   1.5%
Asian
6
   9.0%
7
  10.4%
13
   9.7%
Other
9
  13.4%
3
   4.5%
12
   9.0%
Intraocular Pressure (IOP)   [1] 
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 67 participants 67 participants 134 participants
21.6  (1.78) 21.8  (1.90) 21.7  (1.84)
[1]
Measure Description: IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg).
1.Primary Outcome
Title Mean Change From Baseline in Diurnal Intraocular Pressure (IOP) (Mean of Changes at 09:00 and 11:00 Time Points) at Week 6
Hide Description IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP change was defined as the average of the two changes from baseline (timepoints 9 AM, 11 AM). A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. At each time point, only subjects with a value at both baseline and that time point are included in the calculation of change.
Arm/Group Title Simbrinza + Duotrav Vehicle + Duotrav
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Brinzolamide/brimonidine vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Overall Number of Participants Analyzed 61 67
Mean (Standard Deviation)
Unit of Measure: mmHg
-4.5  (2.69) -2.4  (3.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Simbrinza + Duotrav, Vehicle + Duotrav
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.15
Confidence Interval (2-Sided) 95%
-2.8 to -1.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.342
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Diurnal IOP at Week 6
Hide Description IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP was defined as the average of the two time points measured (9 AM, 11 AM). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Only one eye (study eye) was used for the analyses.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set with non-missing values
Arm/Group Title Simbrinza + Duotrav Vehicle + Duotrav
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Brinzolamide/brimonidine vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Overall Number of Participants Analyzed 61 67
Mean (Standard Deviation)
Unit of Measure: mmHg
17.1  (2.96) 19.4  (3.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Simbrinza + Duotrav, Vehicle + Duotrav
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.15
Confidence Interval (2-Sided) 95%
-2.8 to -1.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.342
Estimation 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 assessed using Goldmann applanation tonometry. Diurnal IOP percentage change was defined as the average of the two changes from baseline (timepoints 9 AM, 11 AM). A more negative percentage change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. At each time point, only subjects with a value at both baseline and that time point are included in the calculation of change.
Arm/Group Title Simbrinza + Duotrav Vehicle + Duotrav
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Brinzolamide/brimonidine vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Overall Number of Participants Analyzed 61 67
Mean (Standard Deviation)
Unit of Measure: percentage change
-20.7  (12.00) -11.1  (13.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Simbrinza + Duotrav, Vehicle + Duotrav
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.98
Confidence Interval (2-Sided) 95%
-13.1 to -6.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.572
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline in IOP (09:00, 11:00) at Week 6
Hide Description IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. At each time point, only subjects with a value at both baseline and that time point are included in the calculation of change.
Arm/Group Title Simbrinza + Duotrav Vehicle + Duotrav
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Brinzolamide/brimonidine vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Overall Number of Participants Analyzed 67 67
Mean (Standard Deviation)
Unit of Measure: mmHg
Baseline 9:00 Hr Number Analyzed 67 participants 67 participants
22.2  (1.84) 22.5  (1.80)
Baseline 11:00 Hr Number Analyzed 67 participants 67 participants
21.4  (1.93) 21.4  (2.26)
Change from Baseline 9:00 Hr Number Analyzed 61 participants 67 participants
-4.4  (3.07) -3.2  (3.40)
Change from Baseline 11:00 Hr Number Analyzed 61 participants 67 participants
-5.4  (2.84) -2.5  (2.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Simbrinza + Duotrav, Vehicle + Duotrav
Comments Change from Baseline in IOP at 9:00
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.33
Confidence Interval (2-Sided) 95%
-2.5 to -0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.576
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Simbrinza + Duotrav, Vehicle + Duotrav
Comments Change from Baseline in IOP at 11:00
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.85
Confidence Interval (2-Sided) 95%
-3.9 to -1.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.506
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6
Hide Description IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. A more negative percentage change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. At each time point, only subjects with a value at both Baseline and that time point are included in the calculation of change.
Arm/Group Title Simbrinza + Duotrav Vehicle + Duotrav
Hide Arm/Group Description:
Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Brinzolamide/brimonidine vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase)
Overall Number of Participants Analyzed 61 67
Mean (Standard Deviation)
Unit of Measure: percentage change
Percent change at 9:00 Hr -20.2  (13.56) -14.1  (15.10)
Percent change at 11:00 Hr -25.0  (12.73) -11.7  (13.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Simbrinza + Duotrav, Vehicle + Duotrav
Comments Percentage Change from Baseline in IOP at 09:00
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.15
Confidence Interval (2-Sided) 95%
-11.2 to -1.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.567
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Simbrinza + Duotrav, Vehicle + Duotrav
Comments Percentage Change from Baseline in IOP at 11:00
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -13.21
Confidence Interval (2-Sided) 95%
-17.8 to -8.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.340
Estimation Comments [Not Specified]
Time Frame Baseline through study completion, an average of 42 days
Adverse Event Reporting Description An Adverse Event (AE) was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Includes all subjects who received a dose of masked investigational product (Safety Analysis Set).
 
Arm/Group Title Simbrinza + Duotrav Vehicle + Duotrav
Hide Arm/Group Description All subjects exposed to brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension plus travoprost 0.004%/timolol 0.5% solution All subjects exposed to brinzolamide/brimonidine vehicle plus travoprost 0.004%/timolol 0.5% solution
All-Cause Mortality
Simbrinza + Duotrav Vehicle + Duotrav
Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   0/67 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Simbrinza + Duotrav Vehicle + Duotrav
Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   1/67 (1.49%) 
Renal and urinary disorders     
Dysuria  1  0/67 (0.00%)  1/67 (1.49%) 
1
Term from vocabulary, MedDRA (21.0)
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 + Duotrav Vehicle + Duotrav
Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   0/67 (0.00%) 
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: WW Brand Medical Director Ophtha, GMA Ophthalmics
Organization: Alcon, A Novartis Division
Phone: 1-888-451-3937
Responsible Party: Alcon Research
ClinicalTrials.gov Identifier: NCT02730871     History of Changes
Other Study ID Numbers: GLJ576-P001
2016-000176-20 ( EudraCT Number )
First Submitted: March 30, 2016
First Posted: April 7, 2016
Results First Submitted: April 23, 2019
Results First Posted: May 17, 2019
Last Update Posted: May 29, 2019