E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ocular Hypertension or Open-Angle Glaucoma |
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E.1.1.1 | Medical condition in easily understood language |
Ocular Hypertension or Glaucoma |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022801 |
E.1.2 | Term | Intraocular pressure |
E.1.2 | System Organ Class | 10022891 - Investigations |
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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 |
Tolerability in the ocular surface (cornea and conjunctiva) and effect on intraocular pressure after a daily dose of the investigational product during 14 days of treatment |
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E.2.2 | Secondary objectives of the trial |
• Local tolerability after each dose.
• Systemic tolerability: Effect on laboratory parameters, physical examination, vital signs and electrocardiogram.
• Changes (if any) of the ocular fundus or visual acuity possibly related to the investigational product.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent prior to any clinical trial-related procedures.
2. Male and female subjects in good or fair general health as assessed by the investigator.
3. Age ≥18 years.
4. Previous history or newly diagnosed IOP (≥21 mmHg) with or without open-angle glaucoma in both eyes.
5. Normal result, or result typical for open-angle glaucoma of the following assessments in both eyes or available results in writting within the last 3 months prior to baseline period i.e. up to 4 months before Day 1, on condition that no new ocular signs or symptoms (e.g. marked deterioration of vision, eye pain) has occurred since then which would justify a repeat examination:
- Visual field 24-2 or equivalent (24-2 Humphrey visual field SITA test, about 5 minutes per eye).
- Optical coherence tomography (OCT).
- Best corrected visual acuity ≥0.5 (20/40) on the Snellen chart, or ≤0.3 logMAR.
- Schirmer test (lacrimation).
- Funduscopy.
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E.4 | Principal exclusion criteria |
Exclusion criteria related to general health
1. Pregnant or breastfeeding females or females with a positive urine pregnancy test at the baseline period and on Day 1 of the treatment period.
2. Females of childbearing potential not willing to use a medically acceptable contraceptive method from enrolment until after the follow-up visit.
• Females of childbearing potential are defined as females who are not post menopausal (amenorrheic without an alternative medical cause) or have not been irreversibly surgical sterilised by hysterectomy, bilateral oophorectomy or bilateral salpingectomy.
• Medically acceptable contraceptive methods include vasectomised sexual partner, tubal occlusion, intrauterine device (copper banded coils only), intrauterine system (for example, Mirena), Depo-Provera, implants (Implanon, Norplan), normal and low dose combined oral pills, ethinylestradiol transdermal system (Evra Patch), and intravaginal device (NuvaRing). True sexual abstinence (starting from enrolment until after the follow-up visit) is also an acceptable contraceptive method.
3. Any current disease or condition that might compromise the respiratory, cardiovascular, endocrine, neurological, haematological, renal, or gastrointestinal function (unless deemed not clinically significant by the investigator and sponsor) such as, but not limited to, uncontrolled arterial hypertension (defined as systolic blood pressure [SBP] >160 mmHg or diastolic blood pressure [DBP] >95 mmHg with or without treatment), acute infection in any of the above mentioned systems, uncontrolled type 1 or type 2 diabetes (defined as persistently varying glucose values, receiving multiple insulin injections per day), bronchial asthma requiring frequent use of corticosteroids, or heart failure (New York Heart Association [NYHA] ≥grade 2).
4. Past history of a chronic or recurring condition that could interfere with treatment according to the investigator’s judgement. History of cancer in the last 5 years (except for cutaneous basal or squamous cell carcinoma resolved by excision).
5. Body temperature (axillary, oral or external auditory canal) ≥37.5°C (only to be checked at the enrolment visit).
6. Intolerability of any components of SYL040012 or placebo.
7. Unable to comply with the clinical trial requirements as judged by the investigator.
Exclusion criteria related to medications or procedures
8. Beta blockers or corticosteroids (other than cutaneous or intra-articular) for the treatment of concurrent diseases, even if sporadically, or any ocular or nasal vasoconstrictor treatment in the last 15 days prior to the first investigational product administration
9. Previous refractive surgery; cataract extraction in the last 6 months.
10. Previous surgery for glaucoma.
11. Participation in a clinical trial within 2 months before the enrolment visit.
12. Use of any other investigational product within 60 days before the enrolment visit.
13. Other drugs for the treatment of concurrent diseases are allowed. However, their dosages should be kept constant throughout the study.
Exclusion criteria related to ocular conditions
14. Use of contact lenses in the last 7 days prior to the first investigational product administration and wearing contact lenses throughout the trial.
15. History of ocular infection or inflammation within the last 3 months before the enrolment visit.
16. Pachymetry result (in the middle of the cornea) >620 micron or <500 micron.
17. Angle-closure or pigmentary glaucoma.
18. Chronic or current acute eye diseases such as scleritis, uveitis, blepharitis, conjunctivitis, or ocular Herpes simplex virus infection.
19. Cup to disc (C/D) ratio more than 0.8.
20. Impossibility to properly visualise the ocular fundus, for example due to vitreous haemorrhage or advanced cataract.
Exclusion criteria related to laboratory findings
21. Relevant abnormal laboratory results as judged by the investigator.
22. Positive screening for hepatitis C virus, hepatitis B surface antigen or human immunodeficiency virus (HIV).
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E.5 End points |
E.5.1 | Primary end point(s) |
Local tolerability:
Includes simple corneal and conjunctival evaluation without corneal endothelium assessment or pachymetry. A slit lamp will be used.
The local tolerability evaluation will include:
Cornea: Corneal epithelium using fluorescein and Bengal pink dye.
Conjunctiva: Palpebral and bulbar conjunctival hyperaemia.
A VAS will be used to assess local tolerability in case of symptoms:
0 = no ocular discomfort and 100 = severe ocular discomfort.
The tolerability variable can be categorised as:
Normal: No corneal or conjunctival alteration observed.
Grade 1: Symptomatic or minimally symptomatic alterations observed, but which do not require intervention or interfere with function.
Grade 2: Symptomatic alterations observed which interfere with the function but not with daily life, and require topical intervention.
Grade 3: Symptomatic alterations observed which interfere with daily life, and require surgical intervention.
This classification is based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continuously during the whole trial and in a daily basis: days 1 to 15 and in the follow-up visit/early termination visit days. |
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E.5.2 | Secondary end point(s) |
• Anterior segment of the eye
• Visual acuity
• Ocular fundus
• Physical examination and vital signs
• Laboratory analyses (haematology, biochemistry, and urinalysis)
• 12-Lead ECG
• Recording of AEs
• VAS of local tolerability in case of symptoms (0 = no ocular discomfort and 100 = severe ocular discomfort).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Continuously 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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The clinical trial will consist of a baseline period, a treatment period and a follow-up visit.
For each subject the duration of the clinical trial will be approximately 7 weeks.
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 21 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 21 |