Trial Outcomes & Findings for Safety and Efficacy of SIMBRINZA® BID as an Adjunctive to DUOTRAV® (NCT NCT02730871)

NCT ID: NCT02730871

Last Updated: 2019-05-29

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

173 participants

Primary outcome timeframe

Baseline, Week 6

Results posted on

2019-05-29

Participant Flow

Subjects were recruited from sites located in Argentina, Australia, Belgium, Chile, Columbia, Germany, Greece, Italy, Malaysia, Poland, Spain, Taiwan, and the United Kingdom.

Of the 173 enrolled, 39 subjects were exited as screen failures prior to randomization. This reporting group includes all randomized subjects (134).

Participant milestones

Participant milestones
Measure
Simbrinza + Duotrav
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)
Vehicle + Duotrav
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 Study
STARTED
67
67
Overall Study
Full Analysis Set (FAS)
67
67
Overall Study
Safety Analysis Set
67
67
Overall Study
COMPLETED
61
67
Overall Study
NOT COMPLETED
6
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Simbrinza + Duotrav
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)
Vehicle + Duotrav
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 Study
Adverse Event
6
0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Simbrinza + Duotrav
n=67 Participants
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)
Vehicle + Duotrav
n=67 Participants
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
n=134 Participants
Total of all reporting groups
Age, Continuous
65.7 years
STANDARD_DEVIATION 13.47 • n=99 Participants
65.7 years
STANDARD_DEVIATION 11.77 • n=107 Participants
65.7 years
STANDARD_DEVIATION 12.60 • n=206 Participants
Sex: Female, Male
Female
32 Participants
n=99 Participants
41 Participants
n=107 Participants
73 Participants
n=206 Participants
Sex: Female, Male
Male
35 Participants
n=99 Participants
26 Participants
n=107 Participants
61 Participants
n=206 Participants
Race/Ethnicity, Customized
White
50 Participants
n=99 Participants
57 Participants
n=107 Participants
107 Participants
n=206 Participants
Race/Ethnicity, Customized
Black or African American
2 Participants
n=99 Participants
0 Participants
n=107 Participants
2 Participants
n=206 Participants
Race/Ethnicity, Customized
Asian
6 Participants
n=99 Participants
7 Participants
n=107 Participants
13 Participants
n=206 Participants
Race/Ethnicity, Customized
Other
9 Participants
n=99 Participants
3 Participants
n=107 Participants
12 Participants
n=206 Participants
Intraocular Pressure (IOP)
21.6 mmHg
STANDARD_DEVIATION 1.78 • n=99 Participants
21.8 mmHg
STANDARD_DEVIATION 1.90 • n=107 Participants
21.7 mmHg
STANDARD_DEVIATION 1.84 • n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Simbrinza + Duotrav
n=61 Participants
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)
Vehicle + Duotrav
n=67 Participants
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)
Mean Change From Baseline in Diurnal Intraocular Pressure (IOP) (Mean of Changes at 09:00 and 11:00 Time Points) at Week 6
-4.5 mmHg
Standard Deviation 2.69
-2.4 mmHg
Standard Deviation 3.01

SECONDARY outcome

Timeframe: Week 6

Population: Full Analysis Set with non-missing values

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.

Outcome measures

Outcome measures
Measure
Simbrinza + Duotrav
n=61 Participants
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)
Vehicle + Duotrav
n=67 Participants
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)
Mean Diurnal IOP at Week 6
17.1 mmHg
Standard Deviation 2.96
19.4 mmHg
Standard Deviation 3.45

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Simbrinza + Duotrav
n=61 Participants
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)
Vehicle + Duotrav
n=67 Participants
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)
Mean Percentage Change From Baseline in Diurnal IOP at Week 6
-20.7 percentage change
Standard Deviation 12.00
-11.1 percentage change
Standard Deviation 13.86

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Simbrinza + Duotrav
n=67 Participants
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)
Vehicle + Duotrav
n=67 Participants
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)
Mean Change From Baseline in IOP (09:00, 11:00) at Week 6
Baseline 9:00 Hr
22.2 mmHg
Standard Deviation 1.84
22.5 mmHg
Standard Deviation 1.80
Mean Change From Baseline in IOP (09:00, 11:00) at Week 6
Baseline 11:00 Hr
21.4 mmHg
Standard Deviation 1.93
21.4 mmHg
Standard Deviation 2.26
Mean Change From Baseline in IOP (09:00, 11:00) at Week 6
Change from Baseline 9:00 Hr
-4.4 mmHg
Standard Deviation 3.07
-3.2 mmHg
Standard Deviation 3.40
Mean Change From Baseline in IOP (09:00, 11:00) at Week 6
Change from Baseline 11:00 Hr
-5.4 mmHg
Standard Deviation 2.84
-2.5 mmHg
Standard Deviation 2.98

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Simbrinza + Duotrav
n=61 Participants
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)
Vehicle + Duotrav
n=67 Participants
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)
Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6
Percent change at 9:00 Hr
-20.2 percentage change
Standard Deviation 13.56
-14.1 percentage change
Standard Deviation 15.10
Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6
Percent change at 11:00 Hr
-25.0 percentage change
Standard Deviation 12.73
-11.7 percentage change
Standard Deviation 13.63

Adverse Events

Simbrinza + Duotrav

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Vehicle + Duotrav

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Simbrinza + Duotrav
n=67 participants at risk
All subjects exposed to brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension plus travoprost 0.004%/timolol 0.5% solution
Vehicle + Duotrav
n=67 participants at risk
All subjects exposed to brinzolamide/brimonidine vehicle plus travoprost 0.004%/timolol 0.5% solution
Renal and urinary disorders
Dysuria
0.00%
0/67 • Baseline through study completion, an average of 42 days
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).
1.5%
1/67 • Baseline through study completion, an average of 42 days
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).

Other adverse events

Adverse event data not reported

Additional Information

WW Brand Medical Director Ophtha, GMA Ophthalmics

Alcon, A Novartis Division

Phone: 1-888-451-3937

Results disclosure agreements

  • Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
  • Publication restrictions are in place

Restriction type: OTHER