Trial Outcomes & Findings for SIMBRINZA® Suspension BID as an Adjunctive to Prostaglandin Analogue (PGA) (NCT NCT02419508)

NCT ID: NCT02419508

Last Updated: 2018-11-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 290 participants
• Primary outcome timeframe: Baseline, Week 6
• Results posted on: 2018-11-15

Participant Flow

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).

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.

Participant milestones

Measure	SIMBRINZA + PGA 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	Vehicle + PGA 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 Study STARTED	96	92
Overall Study Full Analysis Set	95	92
Overall Study Safety Analysis Set	95	92
Overall Study COMPLETED	86	88
Overall Study NOT COMPLETED	10	4

Reasons for withdrawal

Measure	SIMBRINZA + PGA 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	Vehicle + PGA 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 Study Adverse Event	9	3
Overall Study Withdrawal by Subject	1	0
Overall Study Other - Reason not specified	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	SIMBRINZA + PGA n=95 Participants 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	Vehicle + PGA n=92 Participants 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 n=187 Participants Total of all reporting groups
Age, Continuous	66.5 years STANDARD_DEVIATION 10.70 • n=93 Participants	67.9 years STANDARD_DEVIATION 11.65 • n=4 Participants	67.2 years STANDARD_DEVIATION 11.17 • n=27 Participants
Sex: Female, Male Female	55 Participants n=93 Participants	43 Participants n=4 Participants	98 Participants n=27 Participants
Sex: Female, Male Male	40 Participants n=93 Participants	49 Participants n=4 Participants	89 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=93 Participants	29 Participants n=4 Participants	52 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=93 Participants	62 Participants n=4 Participants	134 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Baseline Diurnal IOP	22.8 millimeters mercury (mmHg) STANDARD_DEVIATION 2.39 • n=93 Participants	22.9 millimeters mercury (mmHg) STANDARD_DEVIATION 2.32 • n=4 Participants	22.8 millimeters mercury (mmHg) STANDARD_DEVIATION 2.35 • n=27 Participants
Region of Enrollment Europe, Australia	45 Participants n=93 Participants	44 Participants n=4 Participants	89 Participants n=27 Participants
Region of Enrollment Latin America, Canada	50 Participants n=93 Participants	48 Participants n=4 Participants	98 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

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.

Outcome measures

Measure	SIMBRINZA + PGA n=86 Participants 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	Vehicle + PGA n=88 Participants 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
Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6	-5.6 mmHg Standard Deviation 2.72	-2.1 mmHg Standard Deviation 2.61

SECONDARY outcome

Timeframe: Week 6

Population: FAS with data available

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.

Outcome measures

Measure	SIMBRINZA + PGA n=86 Participants 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	Vehicle + PGA n=88 Participants 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
Mean Diurnal IOP at Week 6	17.2 mmHg Standard Deviation 3.49	20.9 mmHg Standard Deviation 3.59

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

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.

Outcome measures

Measure	SIMBRINZA + PGA n=86 Participants 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	Vehicle + PGA n=88 Participants 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
Mean Percentage Change From Baseline in Diurnal IOP at Week 6	-24.7 percent change Standard Deviation 12.17	-9.5 percent change Standard Deviation 10.92

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

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.

Outcome measures

Measure	SIMBRINZA + PGA n=95 Participants 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	Vehicle + PGA n=92 Participants 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
Mean Change From Baseline in IOP at 11:00 at Week 6 Baseline	22.4 mmHg Standard Deviation 2.70	22.6 mmHg Standard Deviation 2.69
Mean Change From Baseline in IOP at 11:00 at Week 6 Change from baseline	-7.0 mmHg Standard Deviation 3.19	-2.4 mmHg Standard Deviation 2.78

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

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.

Outcome measures

Measure	SIMBRINZA + PGA n=86 Participants 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	Vehicle + PGA n=88 Participants 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
Mean Percentage Change From Baseline in IOP at 11:00 at Week 6	-31.3 percent change Standard Deviation 14.81	-10.8 percent change Standard Deviation 11.86

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

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.

Outcome measures

Measure	SIMBRINZA + PGA n=95 Participants 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	Vehicle + PGA n=92 Participants 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
Mean Change From Baseline in IOP at 09:00 at Week 6 Baseline	23.4 mmHg Standard Deviation 2.40	23.4 mmHg Standard Deviation 2.22
Mean Change From Baseline in IOP at 09:00 at Week 6 Change from baseline	-4.9 mmHg Standard Deviation 3.06	-2.5 mmHg Standard Deviation 2.87

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.

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.

Outcome measures

Measure	SIMBRINZA + PGA n=86 Participants 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	Vehicle + PGA n=88 Participants 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
Mean Percentage Change From Baseline at 09:00 at Week 6	-21.0 percent change Standard Deviation 13.36	-10.9 percent change Standard Deviation 11.83

Adverse Events

SIMBRINZA + PGA

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Vehicle + PGA

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	SIMBRINZA + PGA n=95 participants at risk 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	Vehicle + PGA n=92 participants at risk 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
Cardiac disorders Cardiac failure	1.1% 1/95 • Number of events 1 • Baseline through study completion, an average of 6 weeks. 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).	0.00% 0/92 • Baseline through study completion, an average of 6 weeks. 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).

Other adverse events

Measure	SIMBRINZA + PGA n=95 participants at risk 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	Vehicle + PGA n=92 participants at risk 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
Eye disorders Ocular hyperaemia	5.3% 5/95 • Number of events 9 • Baseline through study completion, an average of 6 weeks. 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).	1.1% 1/92 • Number of events 1 • Baseline through study completion, an average of 6 weeks. 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).
Gastrointestinal disorders Dry mouth	5.3% 5/95 • Number of events 5 • Baseline through study completion, an average of 6 weeks. 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).	0.00% 0/92 • Baseline through study completion, an average of 6 weeks. 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).

Additional Information

Brand Medical Director Ophtha, GMA Ophthalmics

Alcon, A Novartis Division

Phone: 1-888-451-3937

Email: alcon.medinfo@alcon.com

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