| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Open angle glaucoma - intraocular pressure |
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| E.1.1.1 | Medical condition in easily understood language |
| Glaucoma - intraocular pressure |
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| 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 | 18.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10022801 |
| E.1.2 | Term | Intraocular pressure |
| E.1.2 | System Organ Class | 100000004848 |
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| 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 |
| To determine the most effective drug concentration of SYL040012 in the reduction of the intraocular pressure (IOP) after 28 days of treatment. |
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| E.2.2 | Secondary objectives of the trial |
Comparative effect on changes within each treatment group in the mean diurnal IOP value after 14 days of treatment (D14) vs baseline.
The comparison in the mean diurnal IOP changes vs. the active control (Timolol) after 14 and 28 days will be also done.
Changes from baseline in the Glaucoma Quality of Life questionnaire (GQL-15) at the end of the study.
The safety variables are the local and systemic tolerability (comparison after 28 days of treatment vs. screening or baseline, based on when the last pre-treatment assessment was done)
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Age ≥18 years.
Male and female subjects in good or fair general health as assessed by the investigator.
Signed informed consent prior to any clinical trial-related procedures.
Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT).
Unmedicated (post-washout) IOP ≥ 23 mmHg as the mean value of all the assessments performed at 09:00, 12:00, and 15:00 hours at baseline, in the worst eye that must not have a difference greater than 3 mmHg with respect to the other eye.
Corrected visual acuity in each eye +1.0 logMAR or better by ETDRS in each eye (equivalent to 20/200).
Central corneal thickness 480-620 μm in the study eye.
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| E.4 | Principal exclusion criteria |
Pregnant or breastfeeding females or females with a positive pregnancy test at screening or baseline visits.
Females of childbearing potential not willing to use a medically acceptable contraceptive method from enrolment until after the follow-up visit. Medically acceptable contraceptive methods include vasectomised sexual partner, tubal occlusion, intrauterine devices or implants, normal or low dose combination oral pills, ethinylestradiol transdermal system, and intravaginal devices. True sexual abstinence (starting from enrollment until after the follow-up visit) is also an acceptable contraceptive method.
Changes of systemic medication that could have a substantial effect on IOP within 30 days prior to screening, or anticipated during the study.
Known hypersensitivity to any component of the formulations (benzalkonium chloride, etc.), or to topical anesthetics or Timolol maleate or other beta-blocking agents.
Clinically significant abnormalities (as determined by the investigator) in laboratory tests at screening.
Uncontrolled asthma (defined as asthma that does not respond to the maximum guideline-directed therapy) or severe chronic obstructive pulmonary disease; sinus bradycardia, second and third-degree AV block, overt cardiac failure, cardiogenic shock and any other Systemic disease non compatible with the use of Timolol according its current version of the Summary of Product Characteristics.
Severe visual field defect. Presence of a scotoma within 5° of fixation on visual field examination.
Any secondary glaucoma or Ocular hypertension (eg, congenital glaucoma, closed-angle glaucoma, uveitic glaucoma, or pseudoexfoliation syndrome).
IOP ≥ 35 mm Hg in any eye at any of the assessment at 09:00, 12:00, and 15:00 hrs, or mean IOP < 21 mmHg at baseline.
Previous non-laser glaucoma surgery or glaucoma laser procedures (e.g., laser trabeculoplasty) and refractive surgery.
Any ocular surgery or laser treatment, cataract extraction or ocular trauma within 6 months prior to Baseline.
Evidence of ocular infection, inflammation, clinically significant blepharitis or conjunctivitis at baseline (Visit 0), or a history of herpes simplex keratitis
Ocular medication of any kind within 30 days of Visit 0, with the exception of ocular hypotensive medications (which must be washed out according to the provided schedule, see 7.2.3.1) lib scrubs or lubricating drops for dry eye (which may be used until V0); and the use of systemic beta-blockers within 7 days of Visit 0.
Clinically significant ocular disease (e.g. uveitis, severe dry eye (eg, clinically relevant superficial punctate keratitis, epithelial erosions of the cornea, and/or use of dry eye medication [including artificial tears] with a frequency exceeding 8 instillations per day). which might interfere with the study, including glaucomatous damage so severe that washout of ocular hypotensive medications for one month is not judged safe
Any abnormality preventing reliable applanation tonometry of either eye.
Current proliferative diabetic retinopathy or age-related macular degeneration, unless deemed not clinically significant by the Investigator.
Participation in any investigational study within 30 days prior to screening.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The absolute change in mean diurnal IOP after 28 days of treatment
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The mean diurnal IOP will be assessed as the mean value of the assessments at 09:00, 12:00 and 15:00, both at baseline and after 28 days. |
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| E.5.2 | Secondary end point(s) |
- The changes in the mean diurnal IOP value after 14 days of treatment
- The comparison in the mean diurnal IOP change vs. the active control (Timolol) will be also done after 14 and 28 days of treatment
- Changes to the GQL-15 questionnaire.
--Safety objectives will include the assessment of the effect of the treatment on the following parameters:
• VAS of local tolerability (ocular discomfort)
• Visual acuity
• Biomicroscopy
• Pachymetry
• Ophthalmoscopy
• Systemic tolerability:
o Physical examination
o Vital signs
o Laboratory parameters
o Electrocardiogram
• Adverse Events (AEs).
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Continuosly during the whole trial |
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| 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 | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.1.4 | Double blind | No |
| 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 | 5 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 |
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| 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
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 10 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 10 |
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