Safety and Efficacy of Adding AZARGA® Adjunctive to Prostaglandin Therapy

• ClinicalTrials.gov Identifier: NCT01263444
• Recruitment Status: Completed
• First Posted: December 20, 2010
• Results First Posted: May 19, 2014
• Last Update Posted: May 20, 2014
• Sponsor: Alcon Research
• Information provided by (Responsible Party): Alcon Research

Study Description

Brief Summary:

The purpose of this study was to evaluate the safety and efficacy of adding AZARGA® as a single agent to prostaglandin monotherapy in patients with either ocular hypertension or primary open-angle glaucoma.

Condition or disease	Intervention/treatment	Phase
Glaucoma; Ocular Hypertension	Drug: Brinzolamide 1% / timolol 0.5% Fixed Combination; Drug: Habitual prostaglandin monotherapy	Phase 4

Detailed Description:

This study consisted of 3 study visits (Screening/Baseline, Week 4, and Week 12). Eligible patients self-administered the study medication (AZARGA® Eye Drops), adjunct to their current prostaglandin monotherapy for 3 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Adding the Brinzolamide/Timolol Maleate Fixed Combination (AZARGA®) to Ocular Hypertensive or Glaucoma Patients Uncontrolled on Prostaglandin Monotherapy
• Study Start Date: March 2011
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: April 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Azarga; Brinzolamide 1% / timolol 0.5% Fixed Combination administered as 1 drop in study eye(s) twice a day (8:00 AM and 8:00 PM) for 12 weeks, at a 5 minute interval from the habitual prostaglandin monotherapy.	Drug: Brinzolamide 1% / timolol 0.5% Fixed Combination; Other Name: AZARGA®; Drug: Habitual prostaglandin monotherapy; Topical ocular therapy used daily as prescribed; Other Names: Latanoprost; Travoprost; Bimatoprost; Tafluprost

Outcome Measures

Primary Outcome Measures :

1. Mean Change From Baseline in Intraocular Pressure (IOP) at Week 12 [ Time Frame: Baseline, Week 12 ]
   IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry. 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. Only one eye (study eye) contributed to the mean.

Secondary Outcome Measures :

1. Mean Change From Baseline in IOP Per Prostaglandin Group at Week 12 [ Time Frame: Baseline, Week 12 ]
   IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry. 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. Only prostaglandin subgroups with ≥ 15 patients were analyzed. Only one eye (study eye) contributed to the mean.
2. Mean Change From Baseline in IOP at Week 4 [ Time Frame: Baseline, Week 4 ]
   IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry. 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. Only one eye (study eye) contributed to the mean.
3. Percentage of Patients Reaching the Target IOP (≤ 18 mmHg) [ Time Frame: Week 12 ]
   IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Only one eye (study eye) was assessed.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Clinical diagnosis of ocular hypertension, primary open angle (including pigment dispersion) glaucoma in both eyes.
• 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.
• Treated with, and in the Investigator's judgment demonstrated an inadequate response to, prostaglandin monotherapy for a minimum of 4 weeks at Visit 1. Last dose of prostaglandin instilled correctly to put patient within the dosing cycle at Visit 1.
• At Visit 1, have an IOP of ≥ 20 mmHg in at least one eye and ≤ 35 mmHg in both eyes treated with prostaglandin monotherapy.
• Best corrected visual acuity of 1.0 LogMAR or better in each eye.
• In any eye not qualifying as a study eye, IOP should be able to be controlled on no pharmacologic therapy or on prostaglandin monotherapy alone.
• Willing to sign an informed consent form.
• Able to follow instructions and willing and able to attend required study visits.
• Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

• Known medical history of allergy, hypersensitivity or poor tolerance to any component of AZARGA® that is deemed clinically significant in the opinion of the investigator.
• A history of, or at risk for uveitis or cystoid macular edema (CME).
• History of ocular herpes simplex.
• Corneal dystrophies in either eye.
• Concurrent infectious/non infectious conjunctivitis, keratitis or uveitis in either eye (excluding Blepharitis or non-clinically significant conjunctival hyperemia).
• Intraocular conventional surgery or laser surgery in study eye(s) less than 3 months prior to Visit 1.
• 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 apart from glaucoma.
• Use of systemic medications known to affect IOP (e.g. oral beta-adrenergic blockers, alpha-agonists and blockers, angiotensin converting enzyme inhibitors and calcium channel blockers), which have not been on a stable course for 7 days prior to Visit 1 or an anticipated change in the dosage during the course of the study.
• Use of corticosteroids (oral, topical ocular or nasal) within 30 days of Visit 1 and during the course of the study.
• Bronchial asthma or a history of bronchial asthma, bronchial hyper reactivity, or severe chronic obstructive pulmonary disease that would preclude the safe administration of a topical beta-blocker.
• History of severe allergic rhinitis.
• A condition, which in the opinion of the principal investigator, would interfere with optimal participation in the study, or which would present a special risk to the subject.
• Use of any systemic carbonic anhydrase inhibitors (CAI) (e.g. methazolamide [Neptazane], acetazolamide [Diamox]).
• Severely impared renal function.
• History of an allergy to sulphonamides.
• Bronchial asthma or a history of bronchial asthma, bronchial hyper reactivity, severe allergic rhinitis or severe chronic obstructive pulmonary disease that would preclude the safe administration of a topical beta-blocker.
• Pregnant, lactating, or of childbearing potential and not using a reliable method of birth control.
• Any clinically significant, serious, or severe medical condition.
• Participation in any other investigational study within 30 days prior to the screening/baseline visit.
• Other protocol-defined exclusion criteria may apply.

Contacts and Locations

Sponsors and Collaborators

Alcon Research

Investigators

• Study Director: Severine Durier, Pharm. D; Alcon Research

More Information

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT01263444
• Other Study ID Numbers: RDG-10-246; 2010-022948-21 ( Registry Identifier: EudraCT )
• First Posted: December 20, 2010
• Results First Posted: May 19, 2014
• Last Update Posted: May 20, 2014
• Last Verified: May 2014

Keywords provided by Alcon Research:

AZARGA®; Open angle glaucoma; Prostaglandin Therapy

Additional relevant MeSH terms:

Glaucoma; Ocular Hypertension; Eye Diseases; Timolol; Bimatoprost; Travoprost; Latanoprost; Brinzolamide; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Ophthalmic Solutions; Pharmaceutical Solutions; Carbonic Anhydrase Inhibitors; Enzyme Inhibitors