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)

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02339584
• Collaborator: (none)
• Enrollment: 493
• Arms: 2
• Actual Duration (Months): 18.6

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the fixed combination (BID) [Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL eyes drops, suspension] to the unfixed combination (BID) [Brinzolamide 10 mg/mL eye drops, suspension plus Brimonidine 2 mg/mL eyes drops, solution] with respect to intraocular pressure (IOP)-lowering efficacy.

Condition or Disease	Intervention/Treatment	Phase
Open-Angle Glaucoma; Ocular Hypertension	Drug: Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension; Drug: Brinzolamide 10 mg/mL eye drops, suspension; Drug: Brimonidine 2 mg/mL eye drops, solution; Drug: Vehicle	Phase 3

Detailed Description

This study is divided into 2 phases conducted in sequence for a total of 6 visits: Phase I (Screening/Eligibility) which includes a Screening Visit, followed by 2 Eligibility Visits (E1 and E2) and Phase II (Treatment/Follow-up) which includes 3 visits at Week 2, Week 6, and Month 3. Following washout of any IOP-lowering medication, subjects who meet all inclusion/exclusion criteria at both Eligibility visits and had IOP measurements within the specified range during this period will be randomized to Phase II.

Study Design

• Study Type: Interventional
• Actual Enrollment: 493 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL Eye Drops, Suspension Compared to Brinzolamide 10 mg/mL Eye Drops, Suspension Plus Brimonidine 2 mg/mL Eye Drops, Solution in Subjects With Open-Angle Glaucoma or Ocular Hypertension
• Actual Study Start Date: Apr 14, 2015
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension; Drug: Vehicle; Inactive ingredients used as a placebo for masking purposes
Active Comparator: 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	Drug: Brinzolamide 10 mg/mL eye drops, suspension; Other Names: AZOPT™ ; Drug: Brimonidine 2 mg/mL eye drops, solution

Outcome Measures

Primary Outcome Measures

1. Mean Diurnal IOP Change From Baseline at Month 3 [Baseline (Day 0), Month 3]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 95 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of open-angle glaucoma or ocular hypertension insufficiently controlled on monotherapy or currently on multiple IOP-lowering medications;

• Mean IOP measurements within guidelines specified in the protocol. Must not be > 36 mmHg at any time point;

• Able to understand and sign an informed consent form;

• Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

• Women of childbearing potential who are pregnant, test positive for pregnancy, intend to become pregnant during the study period, breast-feeding, or not in agreement to use adequate birth control methods throughout the study;

• Severe central visual field loss in either eye;

• Unable to safely discontinue all IOP-lowering ocular medication(s) for a minimum of 5 (± 1) to 28 (± 1) days prior to E1 Visit;

• Chronic, recurrent or severe inflammatory eye disease;

• Ocular trauma within the past 6 months;

• Ocular infection or ocular inflammation within the past 3 months;

• Clinically significant or progressive retinal disease such as retinal degeneration, diabetic retinopathy, or retinal detachment;

• Best-corrected visual acuity (BCVA) score worse than 55 ETDRS letters (equivalent to approximately 0.60 logMAR, 20/80 Snellen, or 0.25 decimal);

• Other ocular pathology (including severe dry eye) that may preclude the administration of α-adrenergic agonist and/or topical carbonic anhydrase inhibitor (CAI);

• Intraocular surgery within the past 6 months;

• Ocular laser surgery within the past 3 months;

• Any abnormality preventing reliable applanation tonometry;

• Any conditions including severe illness which would make the Subject, in the opinion of the Investigator, unsuitable for the study;

• History of active, severe, unstable or uncontrolled cardiovascular, cerebrovascular, hepatic, or renal disease that would preclude safe administration of a topical α-adrenergic agonist or CAI;

• Recent (within 4 weeks of the E1 Visit) use of high-dose (> 1 g daily) salicylate therapy;

• Current or anticipated treatment with any psychotropic drugs that augment adrenergic response (eg, desipramine, amitriptyline);

• Concurrent use of monoamine oxidase inhibitors (MAOI);

• Concurrent use of glucocorticoids administered by any route;

• Therapy with another investigational agent within 30 days prior to the Screening Visit;

• Hypersensitivity to α-adrenergic agonist drugs, topical or oral CAIs, sulfonamide derivatives, or to any component of the study medications;

• Less than 30 days stable dosing regimen before the Screening Visit of any medications (excluding IOP-lowering treatments) or substances administered by any route and used on a chronic basis that may affect IOP, including but not limited to β-adrenergic blocking agents;

• Use of any additional topical or systemic ocular hypotensive medication during the study;

• Other protocol-specified exclusion criteria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: Clinical Trial Management, Asia, Alcon, A Novartis Division

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT02339584
• Other Study ID Numbers: C-13-013
• First Posted: Jan 15, 2015
• Last Update Posted: Jul 2, 2018
• Last Verified: Aug 1, 2017

• Keywords provided by Alcon Research: OAG; OHT
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Brimonidine Tartrate; Ophthalmic Solutions; Brinzolamide

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 26 study centers located in China (14), Russia (9), and Taiwan (3).
Pre-assignment Detail	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).

Arm/Group Title	Brinz/Brim	Brinz+Brim
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	188	191
COMPLETED	173	176
NOT COMPLETED	15	15

Baseline Characteristics

Arm/Group Title	Brinz/Brim	Brinz+Brim	Total
Arm/Group Description	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	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 of all reporting groups
Overall Participants	172	177	349
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.3 (16.29)	52.6 (16.25)	52.4 (16.25)
Sex: Female, Male (Count of Participants)
Female	97 56.4%	98 55.4%	195 55.9%
Male	75 43.6%	79 44.6%	154 44.1%
Mean Diurnal Intraocular Pressure (IOP) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	24.62 (2.661)	24.59 (2.660)	24.61 (2.657)

Outcome Measures

1. Primary Outcome

Title	Mean Diurnal IOP Change From Baseline at Month 3
Description	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.
Time Frame	Baseline (Day 0), Month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Brinz/Brim	Brinz+Brim
Arm/Group Description	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	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
Measure Participants	169	171
Mean (Standard Error) [mmHg]	-7.2 (0.34)	-7.3 (0.34)

Adverse Events

Time Frame	Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 134 days).
Adverse Event Reporting Description	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.
Arm/Group Title	Brinz/Brim		Brinz+Brim
Arm/Group Description	All subjects exposed to Brinz/Brim		All subjects exposed to Brinz+Brim
All Cause Mortality
	Brinz/Brim		Brinz+Brim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/188 (0%)		0/191 (0%)
Serious Adverse Events
	Brinz/Brim		Brinz+Brim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/188 (2.1%)		4/191 (2.1%)
Ear and labyrinth disorders
Deafness neurosensory	1/188 (0.5%)		0/191 (0%)
Gastrointestinal disorders
Gastritis	0/188 (0%)		1/191 (0.5%)
Pancreatitis acute	1/188 (0.5%)		0/191 (0%)
Injury, poisoning and procedural complications
Ligament injury	1/188 (0.5%)		0/191 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/188 (0%)		1/191 (0.5%)
Nervous system disorders
Diabetic neuropathy	0/188 (0%)		1/191 (0.5%)
Renal and urinary disorders
Renal colic	1/188 (0.5%)		0/191 (0%)
Respiratory, thoracic and mediastinal disorders
Vocal cord leukoplakia	0/188 (0%)		1/191 (0.5%)
Other (Not Including Serious) Adverse Events
	Brinz/Brim		Brinz+Brim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/188 (6.4%)		13/191 (6.8%)
Eye disorders
Conjunctival hyperaemia	12/188 (6.4%)		13/191 (6.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor reserves the right of prior review of any publication or presentation of information related to the study.