Trial Outcomes & Findings for Efficacy and Safety Study of Brinzolamide 1%/Brimonidine 0.2% vs. Brinzolamide 1% and Brimonidine 0.2% (NCT NCT01297517)

Last Updated: 2013-05-21

Results Overview

At the Month 3 (Exit) visit, the 8 am IOP measurement was taken before instillation of study drug. The study drug was instilled approximately 15 minutes after the 8 am measurement. An additional dose was given at 3 pm. 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

1001 participants

Primary outcome timeframe

Month 3

Results posted on

2013-05-21

Participant Flow

Subjects were recruited from 68 study centers in the US.

Of the 1001 enrolled, 341 subjects did not qualify for treatment and were exited without exposure to product. The 660 subjects eligible for treatment were randomized (1:1:1) to study drug. This reporting group includes all randomized subjects, as treated.

Participant milestones

Participant milestones
Measure	Brinzolamide/Brimonidine Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brinzolamide Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brimonidine Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months
Overall Study STARTED	214	226	220
Overall Study COMPLETED	187	214	193
Overall Study NOT COMPLETED	27	12	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Brinzolamide/Brimonidine Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brinzolamide Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brimonidine Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months
Overall Study Adverse Event	21	7	16
Overall Study Lost to Follow-up	1	0	1
Overall Study Patient Decision Unrelated to AE	2	3	7
Overall Study Noncompliance	1	0	0
Overall Study Protocol Violation	1	1	1
Overall Study Inadequate Control of IOP	1	1	2

Baseline Characteristics

Efficacy and Safety Study of Brinzolamide 1%/Brimonidine 0.2% vs. Brinzolamide 1% and Brimonidine 0.2%

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brinzolamide/Brimonidine n=214 Participants Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brinzolamide n=226 Participants Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brimonidine n=220 Participants Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Total n=660 Participants Total of all reporting groups
Age, Customized 18 to 64 years	107 participants n=5 Participants	101 participants n=7 Participants	117 participants n=5 Participants	325 participants n=4 Participants
Age, Customized ≥65 years	107 participants n=5 Participants	125 participants n=7 Participants	103 participants n=5 Participants	335 participants n=4 Participants
Sex: Female, Male Female	140 Participants n=5 Participants	128 Participants n=7 Participants	135 Participants n=5 Participants	403 Participants n=4 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	98 Participants n=7 Participants	85 Participants n=5 Participants	257 Participants n=4 Participants

PRIMARY outcome

Timeframe: Month 3

Population: Intent-to-treat (ITT): All patients 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	Brinzolamide/Brimonidine n=189 Participants Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brinzolamide n=213 Participants Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brimonidine n=192 Participants Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months
Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) 8 am (before study drug instillation)	20.5 millimeters mercury (mm Hg) Standard Error 0.29	21.6 millimeters mercury (mm Hg) Standard Error 0.28	23.3 millimeters mercury (mm Hg) Standard Error 0.29
Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) +2 hrs relative to 8 am dosing	17.2 millimeters mercury (mm Hg) Standard Error 0.29	20.4 millimeters mercury (mm Hg) Standard Error 0.28	19.7 millimeters mercury (mm Hg) Standard Error 0.29
Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) +7 hrs relative to 8 am dosing	18.7 millimeters mercury (mm Hg) Standard Error 0.29	20.4 millimeters mercury (mm Hg) Standard Error 0.28	21.3 millimeters mercury (mm Hg) Standard Error 0.29
Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) +9 hrs relative to 8 am dosing	17.0 millimeters mercury (mm Hg) Standard Error 0.29	20.0 millimeters mercury (mm Hg) Standard Error 0.28	18.8 millimeters mercury (mm Hg) Standard Error 0.29

Adverse Events

Brinzolamide/Brimonidine

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Brinzolamide

Serious events: 6 serious events

Other events: 26 other events

Deaths: 0 deaths

Brimonidine

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Brinzolamide/Brimonidine n=214 participants at risk Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brinzolamide n=226 participants at risk Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brimonidine n=220 participants at risk Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months
Surgical and medical procedures Cardiac pacemaker insertion	0.47% 1/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Ear and labyrinth disorders Vertigo	0.47% 1/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
General disorders Chest pain	0.00% 0/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.91% 2/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Nervous system disorders Amnesia	0.00% 0/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.44% 1/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Blood and lymphatic system disorders Anaemia	0.00% 0/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.44% 1/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Cardiac disorders Angina pectoris	0.00% 0/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.44% 1/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Injury, poisoning and procedural complications Collapse of lung	0.00% 0/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.44% 1/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Surgical and medical procedures Vertebroplasty	0.00% 0/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.44% 1/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Vulval neoplasm	0.00% 0/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.44% 1/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Injury, poisoning and procedural complications Injury	0.00% 0/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.45% 1/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.

Other adverse events

Other adverse events
Measure	Brinzolamide/Brimonidine n=214 participants at risk Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brinzolamide n=226 participants at risk Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brimonidine n=220 participants at risk Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months
Eye disorders Vision blurred	6.5% 14/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	6.6% 15/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.45% 1/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Nervous system disorders Dysgeusia	3.7% 8/214 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	6.2% 14/226 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.	0.00% 0/220 • Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication. This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study 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