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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)

Registration Number
NCT02339584
Lead Sponsor
Alcon Research
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
493
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Brinz+BrimBrimonidine 2 mg/mL eye drops, solutionBrimonidine 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
Brinz/BrimVehicleVehicle 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/BrimBrinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspensionVehicle 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+BrimBrinzolamide 10 mg/mL eye drops, suspensionBrimonidine 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
Primary Outcome Measures
NameTimeMethod
Mean Diurnal IOP Change From Baseline at Month 3Baseline (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.

Secondary Outcome Measures
NameTimeMethod
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