A bioequivalence study Brimonidine tartrate 2 mg/ml & Timolol 5 mg/ml in the treatment of elevated intraocular pressure in adult patients with chronic 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 to assess non-inferiority of Brimonidine tartrate 2 mg/ml & Timolol 5 mg/ml preservative-free eye drops solution (Pharmathen S.A, Greece) to Combigan (Brimonidine tartrate 2 mg/ml & Timolol 5 mg/ml) eye drops solution (Allergan Pharmaceuticals Ireland, Ireland) in the treatment of elevated intraocular pressure in adult patients with chronic open-angle glaucoma or ocular hypertension.
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sumit Arora
Designation
Vice President Clinical Operations
Affiliation
Veeda Clinical Research Ltd.
Address
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad 380 015, India
2nd floor Magnet Park 6, Thaltej
Veeda Clinical Research Ahmedabad Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
Email
Sumit.arora@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 380 015, India
2nd Floor Magnet Park 6 Thaltej Veeda Clinical Research Ahmedabad Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
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 380 015, India
2nd Floor Magnet Park 6 Thaltej Veeda Clinical Research Ahmedabad Ahmadabad GUJARAT 380054 India
Phone
7930013000
Fax
7930013010
Email
Ravi.A1950@veedacr.com
Source of Monetary or Material Support
Pharmathen S.A
Primary Sponsor
Name
Pharmathen SA
Address
6 Dervenakion Street 15351 Pallini Attica, Greece
Tel No.:30 210 66 04 300
Fax No.:30 210 66 66 749
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Veeda Clinical Research Ltd
Shivalik Plaza, Near I.I.M.
Ambawadi, Ahmedabad 380 015, India
Phone: 917930013000
Fax: 917930013010
Brimonidine tartrate 2 mg/ml & Timolol 5 mg/ml preservative-free eye drops solution (Pharmathen S.A, Greece)patient will self-administer one drop of test or reference product in one or both the eyes
Combigan (Brimonidine tartrate 2 mg/ml & Timolol 5 mg/ml) eye drops solution (Allergan Pharmaceuticals Ireland, Ireland)patient will self-administer one drop of reference product in one or both the eyes
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Male and female patients, aged ≥18 years, diagnosed with chronic open-angle glaucoma or ocular hypertension, who in the opinion of the Investigator, were insufficiently controlled on monotherapy of topical beta-blockers.
2. Mean IOP measurements in at least 1 eye, the same eye(s), 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
• Mean IOP must not have been > 36 mmHg in either eye at any time point.
3. Best corrected visual acuity (BCVA) of 20/100 or better in each eye.
4. 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 gradually withdraw the ongoing ocular hypotensive medication and substitute a parasympathomimetic or carbonic anhydrase inhibitor (having shorter washout period) in place of sympathomimetics, alpha-agonist, beta-adrenergic blocking agent, topical prostaglandins and topical prostamides (having longer washout period) as per table 1. 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).
5. Patients must have provided IEC approved written informed consent using the latest version of the IEC informed consent form.
6. Patients must be in good health and free from any clinically significant disease apart from indication under study.
7. Patients able to comply with study procedures in the opinion of the investigator.
8. 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.
9. Patients must be able to safely discontinue use of all ocular hypotensive medication(s) and undergo appropriate washout period.
10. 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 ≤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 in either eye (as measured by gonioscopy).
5. Cup-to-disc ratio >0.80 (horizontal or vertical measurement) in either eye.
6. Unable to safely discontinue IOP-lowering ocular medications per the washout schedule.
7. 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.
8. Ocular trauma within the preceding 6 months.
9. Contraindication to brimonidine tartrate, timolol or sulfonamide therapy or known hypersensitivity to sulfonides or any component of brimonidine tartrate and timolol ophthalmic solution.
10. Use of intraocular corticosteroid implant at any time prior to baseline.
11. Use of contact lens within one week prior to baseline.
12. Ocular laser surgery within the 3 months prior to entry.
13. Use within two weeks prior to baseline of: 1) topical ophthalmic corticosteroid, or 2) topical corticosteroid.
14. Use within one month prior to baseline of: 1) systemic corticosteroid or 2) high-dose (>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).
15. Use within six months prior to baseline of intravitreal or subtenon injection of ophthalmic corticosteroid.
16. Underwent within six months prior to baseline any other intraocular surgery (e.g., cataract surgery).
17. Underwent within 12 months prior to baseline: refractive surgery, filtering surgery for IOP reduction.
18. Amblyopia - only one sighted eye.
19. Clinically significant or progressive retinal disease (e.g., retinal degeneration, diabetic retinopathy, retinal detachment) in either eye.
20. Any abnormality preventing reliable applanation tonometry.
21. History or presence of significant alcoholism or drug abuse in the past one year.
22. Current history of smoking.
23. 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
24. Any form of glaucoma other than open-angle glaucoma.
25. Therapy with an investigational agent within the past 30 days from screening.
26. Clinically significant hematologic and or biochemical abnormalities based on laboratory testing.
27. Patients who are in the investigator s best judgment at risk of visual field or visual acuity worsening as a consequence of participation of trial.
28. Any other conditions, including severe illness, which would make the patient, in the opinion of the Investigator, unsuitable for the study.
29. 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.
30. 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.
31. Major illness, as per investigator discretion, during 3 months before screening
32. Participating in a clinical study within the past 3 months.
33. 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
Not Applicable
Method of Concealment
On-site computer system
Blinding/Masking
Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To evaluate bioequivalence by establishing non-inferiority in terms of efficacy between Brimonidine tartrate 2 mg/ml & Timolol 5 mg/ml preservative-free eye drops solution (Pharmathen S.A, Greece) and Combigan (Brimonidine tartrate 2 mg/ml + Timolol 5 mg/ml) eye drops solution (Allergan Pharmaceuticals Ireland, Ireland) in adult patients with chronic open-angle glaucoma or ocular hypertension.
At each time point (i.e., 9 a.m., and 11 a.m.) on the day of efficacy assessment (Visit 4(week 2), Visit 5(week 6) and Visit 6(week 12)), at least two consecutive measures of IOP will be obtained for each eye using a Goldmann applanation tonometer.
Secondary Outcome
Outcome
TimePoints
• 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.
• 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.)
• 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.)
At each time point (i.e., 9 a.m., and 11 a.m.) on the day of efficacy assessment (Visit 4(week 2), Visit 5(week 6) and Visit 6(week 12)), at least two consecutive measures of IOP will be obtained for each eye using a Goldmann applanation tonometer.
Target Sample Size
Total Sample Size="196" Sample Size from India="196" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="233"
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-inferioritybetween Brimonidine
tartrate 2 mg/ml + Timolol 5 mg/ml preservative-free eye drops solution (Pharmathen S.A, Greece) and Combigan (Brimonidine tartrate 2 mg/ml + Timolol 5 mg/ml) eye
drops solution (Allergan Pharmaceuticals Ireland, Ireland) in the treatment
of elevated intraocular pressure in
adult patients with chronic open angle glaucoma or ocular hypertension at multiple
clinical trial sites.
Patients will be randomized in an assessor-blinded fashion in a 1:1 ratio to receive either Brimonidine tartrate 2 mg/ml + Timolol 5 mg/ml preservative-free eye
drops solution (Pharmathen S.A, Greece) or Combigan (Brimonidine tartrate 2 mg/ml + Timolol 5 mg/ml)
eye drops solution (Allergan Pharmaceuticals Ireland, Ireland) as per
randomization schedule.