CTRI/2020/09/027727 [Registered on: 10/09/2020] Trial Registered Prospectively
Last Modified On:
10/12/2021
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Parallel Group Trial
Public Title of Study
Bioequivalence study between Brinzolamide plus in adult patients with open-angle glaucoma or ocular hypertension.
Scientific Title of Study
A multicentre, randomized, assessor-blinded, active controlled, parallel group,
two arm, bioequivalence study with clinical endpoint between Brinzolamide
10 mg/ml plus 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.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
20-VIN-0084 Version 02 dated 24 July 2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sumit Arora
Designation
Vice President Clinical Operations
Affiliation
Veeda Clinical Research Pvt, Ltd.
Address
Veeda Clinical Research Pvt. Ltd Shivalik Plaza, Near I.I.M.
Ambawadi Ahmedabad, Gujarat 380 015 India
Ahmadabad
GUJARAT
380015
India
Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
Email
Sumit.arora@veedacr.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
Dy. General Manager
Affiliation
Veeda Clinical Research Pvt, Ltd.
Address
Veeda Clinical Research Pvt. Ltd Shivalik Plaza, Near I.I.M.
Ambawadi Ahmedabad, Gujarat 380 015 India
Ahmadabad
GUJARAT
380015
Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
Email
Ravi.A1950@veedacr.com
Details of Contact Person Public Query
Name
Dr Ravi Alamchandani
Designation
Dy. General Manager
Affiliation
Veeda Clinical Research Pvt, Ltd
Address
Veeda Clinical Research Pvt. Ltd Shivalik Plaza, Near I.I.M.
Ambawadi Ahmedabad, Gujarat 380 015 India
Ahmadabad
GUJARAT
22-23, 1st floor, Swagal Complex, Opp. Sneh-Milan Garden. Next to
Mehta Park Party Plot, Majura Gate, Surat 395001, Gujarat. India. Surat GUJARAT
9825573472
drbhavin76@gmail.com
Dr Sonika Shah
Dhadiwal hospital In Coalition with S
Opp. New CBS, Trimbak Road, Nasikhreeji Health care
422002 Nashik MAHARASHTRA
9422768099
navkar.eye@gmail.com
Dr Rani Sujatha
Dr. B.R. Ambedkar Medical College
Room No. 1, I Division
Ophthalmology, Department Dr. B R Ambedkar MedicalCollege Kadugondanahalli,
Bangalore 560045 Bangalore
KARNATAKA Bangalore KARNATAKA
OPD no-01,H Wing,Jay Ganesh Samrajya, office no.122
124,131 133, Spine Road, Nashik Pune Hwy, Bhosari, Pune,
Maharashtra 411039 Pune MAHARASHTRA
9545680252
insightoph@gmail.com
Dr Ashish Saxena
Kanoria Hospital and Research Centre
AirportGandhinagar Highway Village Bhat, Dist. Gandhinagar, Gujarat 382428 Gandhinagar GUJARAT
9824042699 7923969452 drashishsaxenacr@gmail.com
Dr Purvi Raj Bhagat
M & J Western Regional Institute of Ophthalmology
Civil Hospital Campus, Asarwa, Ahmedabad 380016.
Gujarat, India Ahmadabad GUJARAT
9825985265
dr.purvibhagat@yahoo.com
DrSudhir Garg
Maharaja Agrasen Hospital
Near Metro Station Jain Muni Guru Ramkrishan Marg Block C, Shivaji Park, West Punjabi Bagh, Delhi, 110026 West DELHI
9811411198
drskgi2610@gmail.com
Dr Nikhilesh Wairagade
Mahatme Eye bank Eye Hospital
2163-C, Chintaman Nagar Near Rajiv Nagar,
Somalwada, Nagpur 440025, Maharashtra. India Nagpur MAHARASHTRA
9370466075
nikhilesh@mahatmehospital.com
Dr Rekha Khandelwal
N. K. P. Salve Institute Of Medical Sciences & Research Centre
Lata Mangeshkar Hospital, Digdoh hills, Higna Road, Nagpur 440019, Maharashtra, INDIA Nagpur MAHARASHTRA
9823261794 07104665000 rekha.khandelwal@gmail.com
Dr Deval Shah
NETR The Eyecare Clinic
Vision House, opp
Kameshwar School near Jodhpur Cross Road, Satellite
Ahmedabad 380015 Ahmadabad GUJARAT
9426015448
drdevalshah@gmail.com
Dr Vidya Chelerkar
PBMAs H. V. Desai Eye Hospital
S. No. 93, Tarawade Vasti, Mohammadwadi
Hadapsar, Pune 411060 Pune MAHARASHTRA
9960277023 02026970087 vidyachelerkar@gmail.com
Dr Nitin Prabhudesai
Prabhudeai Snperspeciality Eye Clinic
Clinic14, Sakel Society,
Opp. Siddharth Palace Hall, Near Karishma Society &
Joshi Railway Museum, Kothrud Kothrud Pune,
Maharashtra 4 L 1038. Pune MAHARASHTRA
9762007699
ngpmedh@gmail.com
Dr Kumudini Sharma
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Department of Ophthalmology, 5th Floor, New OPD Block, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014 Lucknow UTTAR PRADESH
one drop of reference product in one or both the eyes
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
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 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.
ExclusionCriteria
Details
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 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.
31. 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.
32. Major illness, as per investigator discretion, during 3 months before screening
33. Participating in a clinical study within the past 3 months.
34. Involvement in the planning and or conduct of the study applies to both investigator staff and or staff at the investigational site
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Other
Blinding/Masking
Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To evaluate bioequivalence by establishing non-inferiority in terms of
efficacy 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 adult patients with
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
Outcome
TimePoints
To assess the safety and tolerability profile of the test product and
reference product.
Mean change from baseline to Week 2 and Week 6 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.
ï‚· Mean change from baseline to Week 2, Week 6 and Week 12 in IOP for
each assessment time point (9 a.m. and 11 a.m.)
ï‚· Mean change from baseline to Week 2, Week 6 and Week 12 in IOP
percent for each assessment time point (9 a.m. and 11 a.m.)
Target Sample Size
Total Sample Size="204" Sample Size from India="204" Final Enrollment numbers achieved (Total)= "204" Final Enrollment numbers achieved (India)="204"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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 the
treatment received by the patient, will dispense the investigational product.
Patients will be instructed not to open the container at the clinical trial site
and 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 the
study treatment is to be administered at the site, evaluators will not be in the
room whenever the investigational medicinal product (IMP) is taken out of
the external packaging or the patient is dosed with an IMP. Dosing at site
will be done by unblinded independent site personnel, trained in IP
administration.