Bioequivalence study between Brinzolamide plus in adult patients with open-angle glaucoma or ocular hypertension.

Completed

• Conditions: Disorders of ocular muscles, binocular movement, accommodation and refraction,

• Registration Number: CTRI/2020/09/027727
• Lead Sponsor: Pharmathen SA

Brief Summary

This will be a multicentre, randomized, assessor-blinded, active controlled, parallel group, two arm, bioequivalence study with clinical endpoint establishing non-inferiority between Brinzolamide 10 mg/ml + Brimonidine tartrate 2 mg/ml eye drops suspension (Pharmathen S.A, Greece) and Simbrinza® (Brinzolamide 10 mg/ml + Brimonidine tartrate 2 mg/ml) eye drops suspension (Novartis Europharm Limited, Ireland) in the treatment of elevated intraocular pressure in adult patients with open angle glaucoma or ocular hypertension at multiple clinical trial sites. Patient will be randomized in an assessor-blinded fashion in a 1:1 ratio to receive either Brinzolamide 10 mg/ml + Brimonidine tartrate 2 mg/ml eye drops suspension (Pharmathen S.A, Greece) or Simbrinza® (Brinzolamide 10 mg/ml + Brimonidine tartrate 2 mg/ml) eye drops suspension (Novartis Europharm Limited, Ireland) as per randomization schedule.

An unblinded independent site personnel who will be unblinded to thetreatment received by the patient, will dispense the investigational product.Patients will be instructed not to open the container at the clinical trial siteand open the container only after reaching home and administer the drug.On the day of efficacy assessment (Visit 4, Visit 5 and Visit 6), when thestudy treatment is to be administered at the site, evaluators will not be in theroom whenever the investigational medicinal product (IMP) is taken out ofthe external packaging or the patient is dosed with an IMP. Dosing at sitewill be done by unblinded independent site personnel, trained in IPadministration.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-28
• Last Update Posted: 2021-10-12
• Study Completion: 2021-11-05

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 204

Inclusion Criteria

• Male and female patients, aged more than or equal to 18 years, diagnosed with bilateral or unilateral open-angle glaucoma or ocular hypertension, who in the opinion of the Investigator, were insufficiently controlled on monotherapy or were already on multiple IOP lowering medications.
• Mean IOP measurements in at least 1 eye, the same eyes, must have been: more than or equal 24 mmHg and less than or equal 36 mmHg at the 9 a.m. time point, and more than or equal 21 mmHg and less than or equal 36 mmHg at the 11 a.m. time point at both the Eligibility 1 and Eligibility 2 visits following washout of any IOP lowering medication .Mean IOP must not have been more than 36 mmHg in either eye at any time point.
• Adequate wash-out period prior to baseline of any ocular hypotensive medication see Table 1.
• In order to minimize potential risk to patients due to IOP elevations during the washout period, investigator may choose to substitute a parasympathomimetic or carbonic anhydrase inhibitor in place of a sympathomimetic, alpha-agonist, beta-adrenergic blocking agent, or prostaglandins.
• However, patients must have discontinued all ocular hypotensive medication for the minimum washout period provided in Table 1.
• In case, the patient was being treated with any ocular hypotensive medication containing two drugs, washout period of the drug having a longer washout period should be considered as washout period (e.g. combination of pilocarpine and betaxolol) where the washout should be considered as 4 weeks).
• Medication Washout period Parasympathomimetics (e.g., pilocarpine, carbachol) 5 days wash out, Carbonic Anhydrase Inhibitors (systemic or topical) (e.g., acetazolamide, dorzolamide hydrochloride, brinzolamide) 5 days wash out ,Sympathomimetics (e.g., dipivefrin, epinephrine) 2 weeks wash out, Alpha-agonists (e.g., apraclonidine, brimonidine tartrate, brimonidine tartrate and brinzolamide) 2 weeks wash out, Beta adrenergic blocking agents (e.g., timolol, timolol maleate and dorzolamide hydrochloride, timolol maleate and brimonidine tartrate, levobunolol, betaxolol, metipranolol, carteolol) 4 weeks, Prostaglandin analogs e.g., latanoprost, travoprost, bimatoprost, tafluprost 4 weeks wash out 4.
• Patients must have provided IEC approved written informed consent using the latest version of the IEC informed consent form.
• Patients must be in good health and free from any clinically significant disease apart from indication under study.
• Patients able to comply with study procedures in the opinion of the investigator.
• Study patients must be willing and able to understand and comply with the requirements of the protocol, including attendance at the required scheduled study visits.
• Sexually active women, unless surgically sterile at least 6 months prior to study drug administration or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy [including oral, transdermal, or implanted contraceptives (any hormonal method in conjunction with a secondary method), intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile at least 6 months prior to study drug administration sexual partner for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug.
• Cessation of birth control after this point should be discussed with a responsible physician.

Exclusion Criteria

• Pregnant or lactating females.
• Chronic, recurrent or severe inflammatory eye disease.
• Severe central visual field loss i.e. sensitivity less than or equal 10 dB in more than or equal 2 of the 4 visual field test points closest to the point of fixation in either eye.
• Schaffer angle grade less than 2 degree in either eye as measured by gonioscopy.
• Cup to disc ratio more than 0.80 horizontal or vertical measurement in either eye.
• Best corrected visual acuity BCVA score worse than 55 ETDRS letters 20 by 80 Snellen equivalent.
• Unable to safely discontinue IOP lowering ocular medications per the washout schedule.
• Current or history within 3 months prior to baseline of significant ocular disease, e.g., corneal edema, uveitis, ocular infection, ocular inflammation in either eye.
• Ocular trauma within the preceding 6 months.
• Contraindication to brimonidine tartrate, brinzolamide or sulphonamide therapy or known hypersensitivity to sulfonides or any component of brimonidine tartrate and brinzolamide ophthalmic suspension.
• Use of intraocular corticosteroid implant at any time prior to baseline.
• Use of contact lens within one week prior to baseline.
• Ocular laser surgery within the 3 months prior to entry.
• topical ophthalmic corticosteroid, or 2.
• topical corticosteroid.
• systemic corticosteroid or 2.
• High dose more than 1 g daily salicylate therapy 3.
• monoamine oxidase MAO inhibitor therapy, 4.
• Any antidepressant which affects noradrenergic transmission e.g. tricyclic antidepressants, mianserin or 5.
• Adrenergic augmenting psychotropic drug e.g. desipramine, amitriptyline.
• Use within six months prior to baseline of intravitreal or subtenon injection of ophthalmic corticosteroid.
• Underwent within 12 months prior to baseline: refractive surgery, filtering surgery for IOP reduction.
• Amblyopia only one sighted eye.
• Clinically significant or progressive retinal disease e.g. retinal degeneration, diabetic retinopathy, retinal detachment in either eye.
• Any abnormality preventing reliable applanation tonometry.
• Current history of smoking.
• Active or prior severe, unstable, or uncontrolled cardiovascular, cerebrovascular, hepatic, or renal disease that would prevent safe administration of topical adrenergic agonists or carbonic anhydrase inhibitors, according to the investigator 25.
• Any form of glaucoma other than open angle glaucoma.
• Therapy with an investigational agent within the past 30 days from screening.
• Patients who are in the investigator best judgment at risk of visual field or visual acuity worsening as a consequence of participation of trial.
• Any other conditions, including severe illness, which would make the patient, in the opinion of the Investigator, unsuitable for the study.
• Chronic use of any systemic medication that may affect IOP with less than three month stable dosing regimen i.e. sympathomimetic agents, beta adrenergic blocking agents, alpha agonists, alpha-adrenergic blocking agents, calcium channel blockers, angiotensin converting enzyme inhibitors, etc.
• Use of any prescribed medication during last two weeks or OTC medicinal products during the last one week preceding the first dosing that is affecting the IOP or result in drug-drug interaction with the study drug.
• Participating in a clinical study within the past 3 months.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate bioequivalence by establishing non-inferiority in terms of	Mean change from baseline to week 12 in diurnal IOP [the average of the | IOP measured at 9 a.m. and 11 a.m. time points] of study eye in the test | arm as compared to reference arm.
efficacy between Brinzolamide 10 mg/ml + Brimonidine tartrate 2 mg/ml	Mean change from baseline to week 12 in diurnal IOP [the average of the | IOP measured at 9 a.m. and 11 a.m. time points] of study eye in the test | arm as compared to reference arm.
eye drops suspension (Pharmathen S.A, Greece) and Simbrinza®	Mean change from baseline to week 12 in diurnal IOP [the average of the | IOP measured at 9 a.m. and 11 a.m. time points] of study eye in the test | arm as compared to reference arm.
suspension (Novartis Europharm Limited, Ireland) in adult patients with	Mean change from baseline to week 12 in diurnal IOP [the average of the | IOP measured at 9 a.m. and 11 a.m. time points] of study eye in the test | arm as compared to reference arm.
(Brinzolamide 10 mg/ml + Brimonidine tartrate 2 mg/ml) eye drops	Mean change from baseline to week 12 in diurnal IOP [the average of the | IOP measured at 9 a.m. and 11 a.m. time points] of study eye in the test | arm as compared to reference arm.
open-angle glaucoma or ocular hypertension.	Mean change from baseline to week 12 in diurnal IOP [the average of the | IOP measured at 9 a.m. and 11 a.m. time points] of study eye in the test | arm as compared to reference arm.

Secondary Outcome Measures

Name	Time	Method
To assess the safety and tolerability profile of the test product and	reference product.

Trial Locations

Locations (18)

Ajanta Research Centre; 🇮🇳 Lucknow, UTTAR PRADESH, India

Aster Aadhar Hospital Prerana Hospital Ltd.; 🇮🇳 Kolhapur, MAHARASHTRA, India

Bhavin Eye Hospital; 🇮🇳 Surat, GUJARAT, India

Dhadiwal hospital In Coalition with S; 🇮🇳 Nashik, MAHARASHTRA, India

Dr. B.R. Ambedkar Medical College; 🇮🇳 Bangalore, KARNATAKA, India

GMERS Medical College and Hospital; 🇮🇳 Gandhinagar, GUJARAT, India

Insight Institute of Opthalmology; 🇮🇳 Pune, MAHARASHTRA, India

Kanoria Hospital and Research Centre; 🇮🇳 Gandhinagar, GUJARAT, India

M & J Western Regional Institute of Ophthalmology; 🇮🇳 Ahmadabad, GUJARAT, India

Maharaja Agrasen Hospital; 🇮🇳 West, DELHI, India

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Ajanta Research Centre

🇮🇳Lucknow, UTTAR PRADESH, India

Dr Neeraj Chowdhry

Principal investigator

9839121338

neerajtaurus3@gmail.com