Efficacy and Tolerability of AZARGA® as Replacement Therapy in Patients on COMBIGAN® Therapy in Canada

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01415401
• Collaborator: (none)
• Enrollment: 57
• Arm: 1
• Duration (Months): 21

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the efficacy and tolerability of changing to AZARGA® from prior brimonidine 0.2%/timolol 0.5% fixed combination (COMBIGAN®) therapy in patients with open-angle glaucoma or ocular hypertension and uncontrolled intraocular pressure (IOP).

Condition or Disease	Intervention/Treatment	Phase
Glaucoma; Ocular Hypertension; Open-angle Glaucoma	Drug: Brinzolamide 1% / timolol 0.5% maleate fixed combination	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessing the Efficacy and Tolerability of AZARGA® (Brinzolamide 1%/Timolol 0.5% Fixed Combination) as Replacement Therapy in Patients on COMBIGAN® (Brimonidine 0.2%/Timolol 0.5% Fixed Combination) Therapy in Canada
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZARGA Brinzolamide 1% / timolol 0.5% maleate fixed combination, 1 drop self-administered in study eye(s) twice daily for 8 weeks (8AM and 8PM)	Drug: Brinzolamide 1% / timolol 0.5% maleate fixed combination; Other Names: AZARGA®

Outcome Measures

Primary Outcome Measures

1. Change in IOP at the Final Visit From Prior Brimonidine 0.2%/Timolol 0.5% Fixed Combination (COMBIGAN®) Therapy (i.e. From Baseline) [Baseline, Week 8]

   IOP (fluid pressure inside the eye) was assessed by Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater amount of improvement. One eye was chosen as the study eye, and only data from the study eye were used for the efficacy analysis.

Secondary Outcome Measures

1. Percentage of Subjects Who Reach Target IOP (≤ 18 mmHg) [Week 8]

   IOP (fluid pressure inside the eye) was assessed by Goldmann applanation tonometry and measured in mmHg. A higher IOP can be a greater risk for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye was chosen as the study eye, and only data from the study eye were used for the efficacy analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willing to sign an Informed Consent form.

• Clinical diagnosis of ocular hypertension, exfoliative open-angle or pigment dispersion glaucoma in at least one eye (study eye).

• Be on a stable IOP lowering regimen within 30 days of Screening Visit.

• IOP considered to be safe, in both eyes, in such a way that should assure clinical stability of vision and the optic nerve throughout the study period.

• Willing to discontinue the use of COMBIGAN® prior to receiving the study drug at Visit

• IOP of between 19 and 35 mmHg in at least one eye (which would be the study eye) while on brimonidine/timolol fixed combination therapy.

• Best corrected visual acuity of 6/60 (20/200 Snellen, 1.0 logMAR) or better in each eye.

• Willing to follow instructions and able to attend required study visits.

• Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

• Known history of hypersensitivity to any component of the preparations used in this study.

• Presence of primary or secondary glaucoma not listed in inclusion criterion #2.

• History of ocular herpes simplex.

• Abnormality preventing reliable applanation tonometry.

• Corneal dystrophies.

• Concurrent infectious/noninfectious conjunctivitis, keratitis or uveitis in either eye. Blepharitis or non-clinically significant conjunctival injection is allowed.

• Intraocular conventional surgery or laser surgery in study eye(s) less than 3 months prior to the Screening Visit.

• Risk of visual field or visual acuity worsening as a consequence of participation in the study, in the investigator's best judgment.

• Progressive retinal or optic nerve disease from any cause.

• Women of childbearing potential not using reliable means of birth control for at least 1 month prior to the Screening/Baseline Visit.

• Pregnant or lactating.

• Other protocol-defined exclusion criteria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: Danyel C. Carr, MS, CCRA, Alcon Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT01415401
• Other Study ID Numbers: RDG-11-199
• First Posted: Aug 12, 2011
• Last Update Posted: Jul 1, 2014
• Last Verified: May 1, 2014

• Keywords provided by Alcon Research: Glaucoma; Ocular hypertension; Intraocular pressure (IOP); Open angle glaucoma; Pigment dispersion glaucoma; Pigmentary
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Timolol; Brinzolamide

Study Results

Participant Flow

Recruitment Details	Participants were recruited from 8 study centers located in Canada.
Pre-assignment Detail	Of the 57 enrolled, 3 participants were exited as screen failures. This reporting group includes all participants who received study medication (54).

Arm/Group Title	AZARGA
Arm/Group Description	Brinzolamide 1% / timolol 0.5% maleate fixed combination, 1 drop self-administered in study eye(s) twice daily for 8 weeks (8AM and 8PM)
Period Title: Overall Study
STARTED	54
COMPLETED	47
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	AZARGA
Arm/Group Description	Brinzolamide 1% / timolol 0.5% maleate fixed combination, 1 drop self-administered in study eye(s) twice daily for 8 weeks (8AM and 8PM)
Overall Participants	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.6 (10.37)
Sex: Female, Male (Count of Participants)
Female	28 51.9%
Male	26 48.1%

Outcome Measures

1. Primary Outcome

Title	Change in IOP at the Final Visit From Prior Brimonidine 0.2%/Timolol 0.5% Fixed Combination (COMBIGAN®) Therapy (i.e. From Baseline)
Description	IOP (fluid pressure inside the eye) was assessed by Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater amount of improvement. One eye was chosen as the study eye, and only data from the study eye were used for the efficacy analysis.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who received study medication and had at least one on-therapy study visit. Last observation carried forward (LOCF) was used.

Arm/Group Title	AZARGA
Arm/Group Description	Brinzolamide 1% / timolol 0.5% maleate fixed combination, 1 drop self-administered in study eye(s) twice daily for 8 weeks (8AM and 8PM)
Measure Participants	54
Baseline	22.24 (3.150)
Change from baseline at Week 8	-2.24 (3.928)

2. Secondary Outcome

Title	Percentage of Subjects Who Reach Target IOP (≤ 18 mmHg)
Description	IOP (fluid pressure inside the eye) was assessed by Goldmann applanation tonometry and measured in mmHg. A higher IOP can be a greater risk for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye was chosen as the study eye, and only data from the study eye were used for the efficacy analysis.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who received study medication, completed all study visits, and satisfied inclusion/exclusion criteria. In addition, no imputation methods were employed; therefore only efficacy measurements available at each visit and time point were analyzed.

Arm/Group Title	AZARGA
Arm/Group Description	Brinzolamide 1% / timolol 0.5% maleate fixed combination, 1 drop self-administered in study eye(s) twice daily for 8 weeks (8AM and 8PM)
Measure Participants	47
Number [percentage of participants]	36.2 67%

Adverse Events

Time Frame	Adverse events (AEs) were collected for the duration of the study (1 year, 9 months). This analysis group includes all subjects who received study medication.
Adverse Event Reporting Description	An AE is defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Adverse events were obtained as solicited comments from the study patients and as observations by the Investigator as outlined in the study protocol.
Arm/Group Title	AZARGA
Arm/Group Description	Brinzolamide 1% / timolol 0.5% maleate fixed combination, 1 drop self-administered in study eye(s) twice daily for 8 weeks (8AM and 8PM)
All Cause Mortality
	AZARGA
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	AZARGA
	Affected / at Risk (%)	# Events
Total	1/54 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/54 (1.9%)
Other (Not Including Serious) Adverse Events
	AZARGA
	Affected / at Risk (%)	# Events
Total	0/54 (0%)

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.