E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Open-angle glaucoma and ocular hypertension |
|
E.1.1.1 | Medical condition in easily understood language |
Open-angle glaucoma and ocular hypertension |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10030856 |
E.1.2 | Term | Open-angle glaucoma |
E.1.2 | System Organ Class | 100000004853 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020784 |
E.1.2 | Term | Hypertension ocular |
E.1.2 | System Organ Class | 100000004853 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Brinzolamide 10 mg/mL / brimonidine 2 mg/mL eye drops,
suspension is superior to brinzolamide 10 mg/mL eye drops,
suspension, with respect to IOP-lowering efficacy, and
brinzolamide 10 mg/mL / brimonidine 2 mg/mL eye drops,
suspension is superior to brimonidine 2 mg/mL eye drops,
solution, with respect to IOP-lowering efficacy |
|
E.2.2 | Secondary objectives of the trial |
There is no secondary objectives. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients 18 years of age or older, of either gender, and any
race/ethnicity, diagnosed with open angle glaucoma or ocular
hypertension, who in the opinion of the Investigator are
insufficiently controlled on monotherapy or are already on
multiple IOP-lowering medications.
2. Patients should be able to understand and sign an informed
consent that has been approved by an Institutional Review
Board/Independent Ethics Committee.
3. Mean IOP measurements in at least 1 eye, the same eye(s),
must be:
• ≥ 24 mmHg and ≤ 36 mmHg at the 9 AM time point
and,
• ≥ 21 mmHg and ≤ 36 mmHg at the 11 AM time point at
both E1 and E2 Visits.
IOP must not be > 36 mmHg at any time point. |
|
E.4 | Principal exclusion criteria |
1. Females of childbearing potential (those who are not surgically
sterilized or post-menopausal for at least 1 year) are excluded
from participation in the studyif they meet any one of the
following conditions:
a. are currently pregnant or,
b. have a positive result on the urine pregnancy test at the
Screening Visit or,
c. intend to become pregnant during the study period or,
d. are breast-feeding or,
e. they are not using highly effective birth control measures,
such as:
Hormonal –
oral, implanted, transdermal, or injected
contraceptives;
Mechanical –
spermicide in conjunction with a barrier such
as a condom or diaphragm or IUD.
Patients with Schaffer angle Grade < 2, as measured by
gonioscopy (extreme narrow angle with complete or partial
closure).
3. Patients with a cup/disc ratio (C/D) greater than 0.80
(horizontal or vertical measurement).
4. Patients with severe central visual field loss. Severe central
visual field loss is defined as a sensitivity of less than or equal
to 10 dB in at least 2 of the 4 visual field test points closest to
the point of fixation.
5. Patients who cannot safely discontinue use of all IOPlowering
ocular medication(s) for a minimum period of 5 days
± 1 day to 28 days ± 1 day prior to Eligibility 1 (E1) Visit.
Chronic, recurrent or severe inflammatory eye disease
(ie, scleritis, uveitis, herpes keratitis).
7. Ocular trauma within the past 6 months.
8. Ocular infection or ocular inflammation within the past 3
months.
9. Clinically significant or progressive retinal disease such as
retinal degeneration, diabetic retinopathy, or retinal
detachment.
10. Best-corrected visual acuity (BCVA) score worse than 55
ETDRS letters (equivalent to approximately 20/80 Snellen,
0.60 logMAR, or 0.25 decimal).
11. Other ocular pathology (including severe dry eye) that may, in
the opinion of the Investigator, preclude the administration of
alpha-adrenergic agonist and/or topical carbonic anhydrase
inhibitor (CAI).
12. Intraocular surgery within the past 6 months.
13. Ocular laser surgery within the past 3 months.
14. Any abnormality preventing reliable applanation tonometry.
15. Any other conditions including severe illness which would
make the patient, in the opinion of the Investigator, unsuitable
for the study.
16. History of active, severe, unstable or uncontrolled
cardiovascular (eg, coronary insufficiency, hypertension,
Raynaud’s phenomenon, orthostatic hypotension,
thromboangiitis obliterans), cerebrovascular (eg, cerebral
insufficiency), hepatic, or renal disease that would preclude
the safe administration of a topical alpha-adrenergic agonist or
CAI in the opinion of the investigator.
17. Patients with recent (within 4 weeks of the Eligibility 1 Visit)
use of high-dose (> 1 g daily) salicylate therapy.
18. Current or anticipated treatment with any psychotropic drugs
that augment adrenergic response (eg, desipramine,
amitriptyline).
19. Concurrent use of monoamine oxidase inhibitor.
20. Therapy with another investigational agent within 30 days
prior to the Screening Visit.
21. Hypersensitivity to alpha-adrenergic agonist drugs, topical or
oral CAIs, sulfonamide derivatives, or to any component of
the study medications in the opinion of the Investigator.
22. Less than 30 days stable dosing regimen before the Screening
Visit of any medications or substances administered by any
route and used on a chronic basis that may affect IOP,
including but not limited to, β-adrenergic blocking agents.
23. Use of any additional topical or systemic ocular hypotensive
medication during the study.
24. Concurrent use of glucocorticoids administered by any route. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary:
• Mean diurnal IOP change from baseline (Month 3).
Supportive Efficacy:
• Diurnal IOP change from baseline (Week 2, Week 6)
• IOP (Week 2, Week 6, Month 3)
• IOP change from baseline (Week 2, Week 6, Month 3)
• IOP % change from baseline (Week 2, Week 6, Month 3)
• Percentage of patients with IOP < 18 mmHg at each ontherapy
visit and time point (Week 2, Week 6, Month 3).)
Safety: Pachymetry, fundus parameters, BCVA, slit-lamp exam,
standard automated perimetry, pulse / blood pressure,
Gonioscopy, adverse events. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
There is no secondary endpoint. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
France |
Germany |
Hungary |
Italy |
Latvia |
Lithuania |
Mexico |
New Zealand |
Portugal |
Singapore |
Spain |
Taiwan |
Thailand |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
It is provided into the protocol |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |