Trial Outcomes & Findings for Three Month Efficacy/Safety Study With a 3-Month Safety Extension of Brinzolamide 1%/Brimonidine 0.2% vs. Brinzolamide 1% or Brimonidine 0.2% (NCT NCT01297920)

Last Updated: 2013-07-04

Results Overview

The study drug was instilled at 8 AM and 3 PM (approximately 15 minutes after conducting the IOP measurements). Intraocular pressure was measured by Goldmann applanation tonometry. One eye from each patient was chosen as the study eye and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1062 participants

Primary outcome timeframe

Month 3

Results posted on

2013-07-04

Participant Flow

Subjects were recruited and enrolled from 64 investigational centers in the United States.

Of the 1062 enrolled, 372 subjects did not meet inclusion/exclusion criteria and were exited from the study as screen failures prior to randomization. This reporting group includes all randomized subjects (690), as treated.

Participant milestones

Participant milestones
Measure	Brinz/Brim Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months	Brinzolamide Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months	Brimonidine Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months
Overall Study STARTED	221	234	235
Overall Study COMPLETED	163	207	178
Overall Study NOT COMPLETED	58	27	57

Reasons for withdrawal

Reasons for withdrawal
Measure	Brinz/Brim Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months	Brinzolamide Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months	Brimonidine Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months
Overall Study Adverse Event	42	10	38
Overall Study Patient Decision Unrelated to AE	6	5	2
Overall Study Noncompliance	1	0	0
Overall Study Protocol Violation	1	3	0
Overall Study Inadequate Control of IOP	7	9	17
Overall Study Patient Did Not Meet Entrance Criteria	1	0	0

Baseline Characteristics

Three Month Efficacy/Safety Study With a 3-Month Safety Extension of Brinzolamide 1%/Brimonidine 0.2% vs. Brinzolamide 1% or Brimonidine 0.2%

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brinz/Brim n=221 Participants Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months	Brinzolamide n=234 Participants Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months	Brimonidine n=235 Participants Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months	Total n=690 Participants Total of all reporting groups
Age, Customized 18 to 64 years	99 participants n=5 Participants	113 participants n=7 Participants	115 participants n=5 Participants	327 participants n=4 Participants
Age, Customized ≥65 years	122 participants n=5 Participants	121 participants n=7 Participants	120 participants n=5 Participants	363 participants n=4 Participants
Sex: Female, Male Female	119 Participants n=5 Participants	136 Participants n=7 Participants	132 Participants n=5 Participants	387 Participants n=4 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	98 Participants n=7 Participants	103 Participants n=5 Participants	303 Participants n=4 Participants
Region of Enrollment United States	221 participants n=5 Participants	234 participants n=7 Participants	235 participants n=5 Participants	690 participants n=4 Participants

PRIMARY outcome

Timeframe: Month 3

Population: Intent-to-Treat (ITT): All subjects who received study medication and completed at least 1 scheduled on-therapy study visit. Observed case analysis of the ITT dataset, per randomized treatment assignment.

Outcome measures

Outcome measures
Measure	Brinz/Brim n=196 Participants Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months	Brinzolamide n=216 Participants Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months	Brimonidine n=203 Participants Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months
Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 8 AM (before study drug instillation)	21.1 millimeters mercury (mm HG) Standard Error 0.30	22.0 millimeters mercury (mm HG) Standard Error 0.29	23.2 millimeters mercury (mm HG) Standard Error 0.30
Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 + 2 hours relative to 8 AM dosing	18.0 millimeters mercury (mm HG) Standard Error 0.30	20.8 millimeters mercury (mm HG) Standard Error 0.29	19.9 millimeters mercury (mm HG) Standard Error 0.30
Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 + 7 hours relative to 8 AM dosing	19.5 millimeters mercury (mm HG) Standard Error 0.30	20.7 millimeters mercury (mm HG) Standard Error 0.29	21.5 millimeters mercury (mm HG) Standard Error 0.30
Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 + 9 hours relative to 8 AM dosing	17.2 millimeters mercury (mm HG) Standard Error 0.30	20.4 millimeters mercury (mm HG) Standard Error 0.29	18.9 millimeters mercury (mm HG) Standard Error 0.30

Adverse Events

Brinz/Brim

Serious events: 7 serious events

Other events: 53 other events

Deaths: 0 deaths

Brinzolamide

Serious events: 7 serious events

Other events: 35 other events

Deaths: 0 deaths

Brimonidine

Serious events: 7 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Brinz/Brim n=221 participants at risk Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months	Brinzolamide n=234 participants at risk Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months	Brimonidine n=235 participants at risk Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months
Eye disorders Conjunctivitis	7.2% 16/221 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	0.00% 0/234 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	6.4% 15/235 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
Eye disorders Vision blurred	5.4% 12/221 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	7.7% 18/234 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	0.43% 1/235 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
Eye disorders Eye allergy	6.3% 14/221 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	0.43% 1/234 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	2.1% 5/235 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
Eye disorders Eye irritation	6.3% 14/221 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	2.6% 6/234 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	3.8% 9/235 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
Nervous system disorders Dysgeusia	4.1% 9/221 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	10.3% 24/234 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	0.85% 2/235 • Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.

Additional Information

Matt Walker, PhD, Clinical Project Lead

Alcon Research, Ltd.

Phone: 1-888-451-3937

Email: [email protected]

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