A phase III, multicentre, prospective, randomized, assessor-blinded, two-arm, parallel group, therapeutic non-inferiority 3-month clinical trial to compare the efficacy and safety of a generic fixed combination of brinzolamide 10 mg/mL + brimonidine tartrate 2 mg/mL eye drops suspension (Pharmathen) versus SIMBRINZA®/Alcon 10 mg/mL + 2 mg/mL eye drops suspension in the treatment of elevated intraocular pressure in adult patients with open-angle glaucoma or ocular hypertensio

Phase 1

• Conditions: Open-angle glaucoma (OAG) or ocular hypertension (OHT); MedDRA version: 20.0Level: SOCClassification code 10015919Term: Eye disordersSystem Organ Class: 10015919 - Eye disorders; MedDRA version: 20.0Level: PTClassification code 10030348Term: Open angle glaucomaSystem Organ Class: 10015919 - Eye disorders; MedDRA version: 20.0Level: PTClassification code 10030043Term: Ocular hypertensionSystem Organ Class: 10015919 - Eye disorders; Therapeutic area: Diseases [C] - Eye Diseases [C11]

• Registration Number: EUCTR2020-000079-18-GR
• Lead Sponsor: Pharmathen S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-13
• Last Update Posted: 20 April 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

For inclusion in the study subjects should fulfill ALL of the following criteria:
•Female or male outpatients, of any race or ethnicity, aged at least 18 years at the time of signing the ICF
•Patients diagnosed with bilateral or unilateral open-angle glaucoma (including open-angle glaucoma with pseudoexfoliation or pigment dispersion) and/or ocular hypertension for whom, as per the investigator’s clinical judgment, monotherapy provides insufficient IOP reduction
•Patients who are able to safely discontinue use of all ocular hypotensive medication(s) and undergo appropriate washout period
•Mean IOP measurements in at least one (1) eye (the same eye), must be:
=24 mmHg and =36 mmHg at the 09:00 a.m. time point, and
=21 and =36 mmHg at the 11:00 a.m. time point at both the Eligibility 1 and Eligibility 2 visits after the required washout of any IOP-lowering medication.
•Mean IOP must be =36 mmHg in both eyes at both time points (09:00 a.m. and 11:00 a.m.) of the two Eligibility visits
•If females of childbearing potential, willingness to use an acceptable form of birth control during the clinical trial
•Patients who are able to comprehend and willing to follow the requirements of the study (including availability on scheduled visit dates)
•Patients who are able to understand and willing to provide voluntary written informed consent before any clinical trial-related procedure is performed.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients who meet ANY of the following criteria will be excluded from the study:
•Females who are pregnant, breast feeding, or planning to become pregnant
•Females of childbearing potential who do not agree to utilize an adequate form of contraception
•Schaffer angle grade <2 in either eye, as measured by gonioscopy (extreme narrow angle with complete or partial closure)
•Central corneal thickness (CCT) >620 µm as measured by pachymetry in either eye
•Cup-to-disk ratio (CDR) >0.80 (horizontal or vertical measurement) in either eye
•Severe central visual field loss (i.e., sensitivity =10 decibel [dB] in at least 2 of the 4 visual field test points closest to the point of fixation) in either eye
•Chronic, recurrent, or current severe inflammatory eye disease (e.g., scleritis, uveitis, herpes keratitis) in either eye
•Ocular infection or ocular inflammation within the past 3 months prior to the Screening visit
•Ocular trauma within the past 6 months prior to the Screening visit
•Clinically significant or progressive retinal disease (e.g., retinal degeneration, diabetic retinopathy, retinal detachment) in either eye
•Other ocular pathology (including severe dry eye) in either eye that may, in the opinion of the Investigator, preclude the safe administration of a topical ocular alpha-adrenergic agonist and/or a topical carbonic anhydrase inhibitor
•Intraocular surgery (e.g., cataract surgery) within the past 6 months prior to the Screening visit
•Refractive surgery, filtering surgery, or laser surgery for IOP reduction within the past 12 months prior to the Screening visit
•Planned ocular surgery of any kind during study participation
•Any abnormality that would prevent accurate IOP readings with the applanation tonometry
•Best corrected visual acuity (BCVA) score worse than 55 ETDRS (Early Treatment Diabetic Retinopathy Study) letters (equivalent to approximately 20/80 Snellen, 0.60 logMAR or 0.25 decimal) in either eye
•Severe illness or other condition that would make the patient, in the opinion of the Investigator, unsuitable for the study
•Patients with severe renal impairment (creatinine clearance [CrCl] <30 mL/min) or hyperchloraemic acidosis
•Current or past history of severe, unstable, or uncontrolled cardiovascular, cerebrovascular, hepatic, or renal disease that would preclude the safe administration of a topical ocular alpha-adrenergic agonist and/or a topical carbonic anhydrase inhibitor, as per the Investigator’s clinical judgment
•Use within 4 weeks prior to the Eligibility 1 visit of:
systemic corticosteroid
high-dose (>1 gram daily) salicylate therapy
monoamine oxidase (MAO) inhibitor therapy
any antidepressant which affects noradrenergic transmission (e.g., tricyclic antidepressants, mianserin)
adrenergic-augmenting psychotropic drug (e.g., desipramine, amitriptyline)
any other medication that augments adrenergic response or precludes use of an alpha-adrenergic agonist
•Use within 2 weeks prior to Eligibility 1 visit of topical ophthalmic corticosteroid or topical corticosteroid
•Use within 6 months prior to Eligibility 1 visit of intravitreal or subtenon injection of ophthalmic corticosteroid
•Use at any time prior to Eligibility 1 visit of intraocular corticosteroid implant
•Patients who currently receive treatment with any investigational drug/device/intervention or who have received any investigational product within 30 days or 5 half-lives of the investigational agent (whichever is longer) before the scree

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: At Month 3;Secondary Objective: To compare the safety and tolerability profile of the generic BBFC 1%/0.2% ophthalmic suspension BID/Pharmathen (test product) versus SIMBRINZA® (BBFC 1%/0.2% ophthalmic suspension BID)/Alcon (reference product) with respect to treatment-emergent ocular and systemic AE and adverse drug reaction (ADR) occurrence and treatment discontinuation due to ADR occurrence over the 3-month treatment period, in adult patients with OAG or OHT. ;Main Objective: To demonstrate that the generic BBFC 1%/0.2% ophthalmic suspension BID/Pharmathen (test product) is non-inferior to SIMBRINZA® (BBFC 1%/0.2% ophthalmic suspension BID)/Alcon (reference product) with respect to IOP-lowering efficacy at Month 3, in adult patients with OAG or OHT.;Primary end point(s): •Difference between the test and reference product in the mean change from baseline in diurnal IOP at Month 3 (patient IOP changes averaged over the 09:00 a.m. and 11:00 a.m. time points).