CTRI/2023/06/054478 [Registered on: 27/06/2023] Trial Registered Prospectively
Last Modified On:
02/07/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A multicenter clinical trial for the comparison of efficacy and safety in the treatment of elevated intraocular pressure in adult patients with glaucoma.
Scientific Title of Study
A multicenter, randomized, assessor-blinded, active controlled, parallel group, two arm, non-inferiority clinical trial for the comparison of efficacy and safety of a preservative-free Brinzolamide 10mg/ml + Brimonidine tartrate 2 mg/ml eye drops suspension (AZAD Pharma AG, Switzerland) 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
22-VIN-0095 Version 01 dated 01 Mar 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Sivakumar Vaidyanathan
Designation
COO- Clinical Trials
Affiliation
Veeda Clinical Research Ltd
Address
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M., Ambawadi,
Ahmedabad
Ahmadabad GUJARAT 380015 India
Phone
9167977840
Fax
Email
sivakumar.vaidyanathan@veedacr.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical Research Ltd
Address
Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M., Ambawadi, Ahmedabad
Ahmadabad GUJARAT 380015 India
Phone
9687306158
Fax
Email
Ravi.A1950@veedacr.com
Details of Contact Person Public Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical Research Ltd
Address
Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M., Ambawadi, Ahmedabad
Ahmadabad GUJARAT 380015 India
Phone
9687306158
Fax
Email
Ravi.A1950@veedacr.com
Source of Monetary or Material Support
AZAD Pharma AG
Durachweg 15CH-8200 Schaffhausen, Switzerland
Primary Sponsor
Name
AZAD Pharma AG
Address
Durachweg 15CH-8200 Schaffhausen, Switzerland
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Veeda Clinical Research Limited
Veeda Clinical Research Pvt. Ltd., Shivalik Plaza, Near I.I.M., Ambawadi, Ahmedabad – 380015
Eye care Super specialty Hospital, 2nd Floor, Shri Raj Center, Above ADC Bank, Opp. Vasna Bus Stand, Vasna, Ahmedabad-380007 Ahmadabad GUJARAT
9824025427
drmahendrathakkar@gmail.com
Dr Anjali Sapar
Insight Institute of Opthalmology
Insight Institute of Ophthalmology OPD no-01,H wing, PI OPD, second floor, Jay Ganesh Samrajya,
office no.122- 124,131-133, Spine Road, Nashik - Pune Hwy, Bhosari, Pune, Maharashtra-411039, Pune MAHARASHTRA
Kanoria Hospital And Research Centre,
Clinical Research Department, Ground floor, Building No. 02
Airport- Gandhinagar Highway, Village-Bhat Gandhinagar
Gujarat - 382428 India Gandhinagar GUJARAT
7016299035
drmiralprajapati1994@gmail.com
Dr PRAMOD KUMAR
King George’s Medical University
Room No.4, Department of Opthalmology, Gate No. 2 Ground Floor, King George Medical University, Shahmina Shah Road, Lucknow 226003 Lucknow UTTAR PRADESH
1st Floor, KayDee House,
Above Union Bank of India,
Opp.Gujarat Gas, Parimal Garden Cross Road, CG Road- 380006 Ahmadabad GUJARAT
7999999344
netralaya.rch@gmail.com
Dr Abhishek Chandra
Netrodaya The Eye City LLP
Arazi No. 651 & 652 , Near Dafi Toll Tax, NH2, Varanasi- 221011 Varanasi UTTAR PRADESH
9651726602
abhishekvinita@gmail.com
Dr Garima Chadda
SAI ORTHO & EYE CARE
A-501,A Wing, 5th Floor,
Neeti Gaurav Complex
Central Bazar Road,
Ramdaspeth, Nagpur - 440010 Nagpur MAHARASHTRA
9370258687
drgarimac@yahoo.co.in
Dr Pooja Bhomaj
Shanti Saroj Netralaya
OPD No.2, First floor, Shanti Saroj Netralay, Near Relience Pump, Central Bank, Sangali Road, Miraj, Sangli-Miraj Kupwad, Maharashtra-416410. Sangli MAHARASHTRA
IEC RadianceHospital Pvt. Ltd. And Purohit Nursing Home
Approved
IEC-Saishwari Clinic -Hospital for Mental Health
Approved
IEC-Saishwari clinical Hospital for mental health
Approved
Ikon Ethics committee for Research
Approved
Janta Hospital Ethics Commitee
Approved
Kanoria Ethics Committee
Approved
Meditrina Institute Ethics Committee
Approved
Netrodaya Institutional Ethics Committee
Approved
Sangini Hospital Ethics Committee
Approved
Sangini Hospital Ethics Committee
Approved
Sangini Hospital Ethics Committee
Approved
Sangini Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: H401||Open-angle glaucoma,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Brinzolamide 10mg/ml &
Brimonidine tartrate 2 mg/ml
eye drops suspension by AZAD Pharma AG
Each study patient will self-administer one drop of test or reference product in the study eye. The patient may also administer in non-study eye as per investigators suggestion (if needed). Eye drop will be instilled in lower conjunctival sac, two times daily, at approximately 09:00 a.m. (±30 minutes) and 09:00 p.m. (±30 minutes) for 12 weeks.
During study visits, designated unblinded independent site personnel will
administered the 9 a.m. dose after IOP measurement.
Each study patient will self-administer one drop of test or reference product in the study eye. The patient may also administer in non-study eye as per investigators suggestion (if needed). Eye drop will be instilled in lower conjunctival sac, two times daily, at approximately 09:00 a.m. (±30 minutes) and 09:00 p.m. (±30 minutes) for 12 weeks.
During study visits, designated unblinded independent site personnel will
administered the 9 a.m. dose after IOP measurement.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Male and female patients, aged 18-75 years (both inclusive), 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 one eye (the same eye), must have been:
▪ ≥ 24 mmHg and ≤ 36 mmHg at the 9 a.m. time point, and
▪ ≥ 21 mmHg and ≤ 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.
â–ª Mean IOP must not have been > 36 mmHg in either eye at any time point.
3. Adequate wash-out period prior to baseline of any ocular hypotensive medication.
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 medication(s) and undergo appropriate washout period.
9. Sexually active women, unless surgically sterile (at least 6 months prior to study drug administration).
ExclusionCriteria
Details
1. Pregnant or lactating females.
2. Chronic, recurrent or severe inflammatory eye disease.
3. Severe central visual field loss (i.e., sensitivity ≤10 dB in ≥2 of the 4 visual field test points closest to the point of fixation) in either eye.
4. Schaffer angle grade <2 degree in either eye (as measured by gonioscopy).
5. Cup-to-disc ratio >0.80 (horizontal or vertical measurement) in either eye.
6. Best corrected visual acuity (BCVA) score worse than 55 ETDRS letters (20/80 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, corneal ulcerin either eye or corneal foreign body.
9. Ocular trauma within the preceding 6 months.
10. Contraindication to brimonidine tartrate, brinzolamide or sulfonamide 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. Active smoker at the time of screening.
24. Active or prior severe, unstable, or uncontrolled cardiovascular, cerebrovascular, hepatic, or renal disease that would prevent safe administration of topical a-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 as judged by investigator.
28. Patients who are at risk of visual field or visual acuity worsening as a consequence of participation of trial as per Investigator discretion.
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. Pupil with inadequate ability to dilate sufficiently for peripheral retinal examination.
35. Patients with risk of angle closure or evidence of acute, intermittent or chronic angle closure.
36. History or evidence of severe inflammatory eye disease (i.e. uveitis, retinitis, scleritis) in one or both eyes.
37. Patients with severe allergic rhinitis.
Method of Generating Random Sequence
Other
Method of Concealment
Other
Blinding/Masking
Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
The primary efficacy endpoint is 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.
• Screening
• Visit 2 – Eligibility Visit (At the end of the washout period for patients who already had received IOP lowering medications)
• Visit 3 (3-8 days after eligibility (Visit 2))
• Visit 4 –Follow up Visit(week 2)
• Visit 5 –Follow up Visit(week 6)
• Visit 6 –End of study(week 12)
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. & 11 a.m-assessment time points] of study eye in the test arm as compared to reference arm using ANCOVA.
• Mean change from baseline to Week 2, 6 & Week 12 in IOP & IOP percent for each assessment time point.
• Ocular tolerance – The difference between the test & reference products with respect to ocular comfort level score and conjunctival hyperemia at baseline-Day 1 and Week 12.
Target Sample Size
Total Sample Size="208" Sample Size from India="208" Final Enrollment numbers achieved (Total)= "208" Final Enrollment numbers achieved (India)="208"
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 multicenter, randomized, assessor-blinded, active
controlled, parallel group, two arm, non-inferiority clinical trial for the comparison
of efficacy and safety of Brinzolamide 10mg/ml & Brimonidine tartrate 2
mg/ml eye drops suspension (AZAD Pharma AG, Switzerland) 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.
Blinding will be performed using identical boxesin primary packaging in the
two groups, and in the replacement of the commercial labels for the comparator(reference product) in the
bottles. An unblinded independent site personnel will dispense the
investigational medicinalproducts, collect used and unused products and administer the treatment to
the patient at the clinic after the IOP measurement and these site personnel will not participate in
the clinical trial assessments (including IOP measurements)
in order to minimize potential bias, and will be instructed not to discuss
about the study drugs with
IOP assessors, and other study personnel.
Each study patient will self-administer one drop of test or reference
product in the study eye. The patient may also administer in non-study eye as
per investigators suggestion (if needed). Eye drop will be instilled in lower
conjunctival sac, two times daily, at approximately 09:00 a.m. (±30 minutes)
and 09:00 p.m. (±30 minutes) for 12 weeks. During study visits, designated
unblinded independent site personnel will administered the 9 a.m. dose after
IOP measurement.
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 IMP is taken out of the external packaging
or the patient is dosed with a IMP.
Dosing at site will be done by unblinded independent site personnel, trained in IP administration.