Bioequivalence study between Brinzolamide plus in adult patients with open-angle glaucoma or ocular hypertension.
- Conditions
- Health Condition 1: H49-H52- Disorders of ocular muscles, binocular movement, accommodation and refraction
- Registration Number
- CTRI/2020/09/027727
- Lead Sponsor
- Pharmathen SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 204
1. 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.
2. 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.
3. 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).
Table 1. 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.
5. Patients must be in good health and free from any clinically significant disease apart from indication under study.
6. Patients able to comply with study procedures in the opinion of the investigator.
7. 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.
8. Patients must be able to safely discontinue use of all ocular hypotensive medications and undergo appropriate washout period.
9. 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 administra
1. Pregnant or lactating females.
2. Chronic, recurrent or severe inflammatory eye disease.
3. 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.
4. Schaffer angle grade less than 2 degree in either eye as measured by gonioscopy.
5. Cup to disc ratio more than 0.80 horizontal or vertical measurement in either eye.
6. Best corrected visual acuity BCVA score worse than 55 ETDRS letters 20 by 80 Snellen equivalent.
7. Unable to safely discontinue IOP lowering ocular medications per the washout schedule.
8. 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.
9. Ocular trauma within the preceding 6 months.
10. Contraindication to brimonidine tartrate, brinzolamide or sulphonamide therapy or known hypersensitivity to sulfonides or any component of brimonidine tartrate and brinzolamide ophthalmic suspension.
11. Use of intraocular corticosteroid implant at any time prior to baseline.
12. Use of contact lens within one week prior to baseline.
13. Ocular laser surgery within the 3 months prior to entry.
14. Use within two weeks prior to baseline of 1. topical ophthalmic corticosteroid, or 2. topical corticosteroid.
15. Use within one month prior to baseline of 1. 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.
16. Use within six months prior to baseline of intravitreal or subtenon injection of ophthalmic corticosteroid.
17. Underwent within six months prior to baseline any other intraocular surgery e.g. cataract surgery.
18. Underwent within 12 months prior to baseline: refractive surgery, filtering surgery for IOP reduction.
19. Amblyopia only one sighted eye.
20. Clinically significant or progressive retinal disease e.g. retinal degeneration, diabetic retinopathy, retinal detachment in either eye.
21. Any abnormality preventing reliable applanation tonometry.
22. History or presence of significant alcoholism or drug abuse in the past one year.
23. Current history of smoking.
24. 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.
26. Therapy with an investigational agent within the past 30 days from screening.
27. Clinically significant hematologic and or biochemical abnormalities based on laboratory testing.
28. Patients who are in the investigator best judgment at risk of visual field or visual acuity worsening as a consequence of participation of trial.
29. Any other conditions, including severe illness, which would make the patient, in the opinion of the Investigator, unsuitable for the study.
30. Chronic use of any systemic medication that may affect IOP with less
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 <br/ ><br>efficacy between Brinzolamide 10 mg/ml + Brimonidine tartrate 2 mg/ml <br/ ><br>eye drops suspension (Pharmathen S.A, Greece) and Simbrinza�® <br/ ><br>(Brinzolamide 10 mg/ml + Brimonidine tartrate 2 mg/ml) eye drops <br/ ><br>suspension (Novartis Europharm Limited, Ireland) in adult patients with <br/ ><br>open-angle glaucoma or ocular hypertension.Timepoint: Mean change from baseline to week 12 in diurnal IOP [the average of the <br/ ><br>IOP measured at 9 a.m. and 11 a.m. time points] of study eye in the test <br/ ><br>arm as compared to reference arm.
- Secondary Outcome Measures
Name Time Method To assess the safety and tolerability profile of the test product and <br/ ><br>reference product.Timepoint: Mean change from baseline to Week 2 and Week 6 in diurnal IOP [the <br/ ><br>average of the IOP measured at 9 a.m. and 11 a.m. time points] of study <br/ ><br>eye in the test arm as compared to reference arm. <br/ ><br>ïâ??· Mean change from baseline to Week 2, Week 6 and Week 12 in IOP for <br/ ><br>each assessment time point (9 a.m. and 11 a.m.) <br/ ><br>ïâ??· Mean change from baseline to Week 2, Week 6 and Week 12 in IOP <br/ ><br>percent for each assessment time point (9 a.m. and 11 a.m.)