Trial Outcomes & Findings for Efficacy and Safety of Brinzolamide/Brimonidine Fixed Combination BID Compared to Brinzolamide BID Plus Brimonidine BID in Subjects With Open-Angle Glaucoma (OAG) or Ocular Hypertension (OHT) (NCT NCT02339584)

Last Updated: 2018-07-02

Results Overview

IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the three timepoints measured: 9 AM, +2 Hrs and +7Hrs. Baseline was the average of the values for 2 eligibility visits. If one of the values was missing, the other non-missing value was taken as the baseline. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates greater improvement, ie, a reduction of IOP. Only one eye (study eye) contributed to the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

493 participants

Primary outcome timeframe

Baseline (Day 0), Month 3

Results posted on

2018-07-02

Participant Flow

Subjects were recruited from 26 study centers located in China (14), Russia (9), and Taiwan (3).

Of the 493 enrolled, 64 subjects were exited as screen failures and another 50 discontinued prior to randomization. This reporting group includes all randomized subjects (379).

Participant milestones

Participant milestones
Measure	Brinz/Brim Vehicle solution, 1 drop, followed by Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) twice daily (BID) for 3 months	Brinz+Brim Brimonidine 2 mg/mL eye drops, solution, 1 drop, followed by Brinzolamide 10 mg/mL eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) BID for 3 months
Overall Study STARTED	188	191
Overall Study COMPLETED	173	176
Overall Study NOT COMPLETED	15	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Brinz/Brim Vehicle solution, 1 drop, followed by Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) twice daily (BID) for 3 months	Brinz+Brim Brimonidine 2 mg/mL eye drops, solution, 1 drop, followed by Brinzolamide 10 mg/mL eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) BID for 3 months
Overall Study Adverse Event	11	7
Overall Study Lack of Efficacy	0	1
Overall Study Physician Decision	1	2
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	2	4

Baseline Characteristics

Efficacy and Safety of Brinzolamide/Brimonidine Fixed Combination BID Compared to Brinzolamide BID Plus Brimonidine BID in Subjects With Open-Angle Glaucoma (OAG) or Ocular Hypertension (OHT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brinz/Brim n=172 Participants Vehicle solution, 1 drop, followed by Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) twice daily (BID) for 3 months	Brinz+Brim n=177 Participants Brimonidine 2 mg/mL eye drops, solution, 1 drop, followed by Brinzolamide 10 mg/mL eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) BID for 3 months	Total n=349 Participants Total of all reporting groups
Age, Continuous	52.3 years STANDARD_DEVIATION 16.29 • n=5 Participants	52.6 years STANDARD_DEVIATION 16.25 • n=7 Participants	52.4 years STANDARD_DEVIATION 16.25 • n=5 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	98 Participants n=7 Participants	195 Participants n=5 Participants
Sex: Female, Male Male	75 Participants n=5 Participants	79 Participants n=7 Participants	154 Participants n=5 Participants
Mean Diurnal Intraocular Pressure (IOP)	24.62 mmHg STANDARD_DEVIATION 2.661 • n=5 Participants	24.59 mmHg STANDARD_DEVIATION 2.660 • n=7 Participants	24.61 mmHg STANDARD_DEVIATION 2.657 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0), Month 3

Population: Per Protocol Analysis Set. Missing Month 3 data were imputed using a last observation carried forward method (LOCF).

Outcome measures

Outcome measures
Measure	Brinz/Brim n=169 Participants Vehicle solution, 1 drop, followed by Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) twice daily (BID) for 3 months	Brinz+Brim n=171 Participants Brimonidine 2 mg/mL eye drops, solution, 1 drop, followed by Brinzolamide 10 mg/mL eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) BID for 3 months
Mean Diurnal IOP Change From Baseline at Month 3	-7.2 mmHg Standard Error 0.34	-7.3 mmHg Standard Error 0.34

Adverse Events

Brinz/Brim

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Brinz+Brim

Serious events: 4 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Brinz/Brim n=188 participants at risk All subjects exposed to Brinz/Brim	Brinz+Brim n=191 participants at risk All subjects exposed to Brinz+Brim
Ear and labyrinth disorders Deafness neurosensory	0.53% 1/188 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.	0.00% 0/191 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.
Gastrointestinal disorders Gastritis	0.00% 0/188 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.	0.52% 1/191 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.
Gastrointestinal disorders Pancreatitis acute	0.53% 1/188 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.	0.00% 0/191 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.
Injury, poisoning and procedural complications Ligament injury	0.53% 1/188 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.	0.00% 0/191 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/188 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.	0.52% 1/191 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.
Nervous system disorders Diabetic neuropathy	0.00% 0/188 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.	0.52% 1/191 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.
Renal and urinary disorders Renal colic	0.53% 1/188 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.	0.00% 0/191 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.
Respiratory, thoracic and mediastinal disorders Vocal cord leukoplakia	0.00% 0/188 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.	0.52% 1/191 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.

Other adverse events

Other adverse events
Measure	Brinz/Brim n=188 participants at risk All subjects exposed to Brinz/Brim	Brinz+Brim n=191 participants at risk All subjects exposed to Brinz+Brim
Eye disorders Conjunctival hyperaemia	6.4% 12/188 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.	6.8% 13/191 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days). An AE was defined as any untoward medical occurrence in a subject who is administered study treatment regardless of whether the event has a causal relationship with the treatment. This analysis includes all subjects who received at least 1 dose of study medication. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the protocol. Ocular AEs are presented for both study eye and non-study eye combined.

Additional Information

Clinical Scientific Associate Director, GCRA, GDD

Enter Alcon, A Novartis Division

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