E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate or severe dry eye syndrome |
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E.1.1.1 | Medical condition in easily understood language |
moderate or severe dry eye syndrome |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013774 |
E.1.2 | Term | Dry eye |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 |
The primary objective of the study is to establish the effective dose/dose regimen of RP101 in post-menopausal women with moderate to severe dry eye syndrome applying RP101 ophthalmic sterile solution or matching placebo (vehicle) once (q.d.) or twice a day (b.i.d.) for 3 months |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: - to evaluate the safety and tolerability of the treatment - to evaluate as exploratory variables tear film osmolarity and corneal pachymetry in specific substudies - to evaluate the pharmacokinetics (PK) of serum 17-β-oestradiol after the 1st and the last dose (only PK substudy)
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PK substudy included in the main protocol. The objective is to evaluate the pharmacokinetics (PK) of serum 17-β-oestradiol after the 1st and the last dose |
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E.3 | Principal inclusion criteria |
1.Informed consent: signed written informed consent before inclusion in the study 2.Sex and menopause: postmenopausal women; postmenopausal condition defined as final menstrual period at least 3 years before the screening 3.Dry eye syndrome: patients with moderate to severe dry eye syndrome 4.Schirmer’s test type II: Schirmer’s test with anaesthesia ≤ 7 mm/5 min in the worse eye (study eye) 5.Fluorescein: corneal fluorescein staining score ≥ 2.0 in one or more regions of the worse eye (study eye) and ≤ 10 in total across all 5 corneal regions according to the NEI scale 6.Tear film breakup time: TFBUT ≤ 10 sec in the worse eye (study eye) 7.Visual acuity: corrected visual acuity ≥ 20/200 in each eye 8.Symptoms: at least 2 of the typical dry eye syndrome symptoms since at least 3 months before the screening: foreign body sensation, burning/stinging, redness, tearing, pain, itching, blurred vision, photophobia, eyelid swelling, moisture and mucous discharge 9.Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
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E.4 | Principal exclusion criteria |
1.Hysterectomy: women younger than 55 with partial or complete hysterectomy 2.Meibomian gland dysfunction: severe Meibomian gland dysfunction defined as lid deformity, marked lid margin hyperaemia or severe Meibomian gland loss 3.Ophthalmic treatment: current use of topical ophthalmic medications other than ocular lubricants or artificial tears within 30 days before the screening 4.Ocular infection and inflammation: presence of any bacterial or viral or fungal infection in either eye or active inflammation not related to dry eye disease (i.e. follicular conjunctivitis, iris or preauricular adenopathy) in either eye 5.Ophthalmic diseases: severe forms of ophthalmic surface diseases e.g. ocular pemphigoid, Sjögren’s disease, exposure keratitis 6.Ophthalmic surgery: history of ophthalmic surgery or trauma in the last 6 months; history of laser-assisted in situ keratomileusis (LASIK) in the previous 12 months 7.Intraocular pressure: intraocular pressure >21 mmHg 8.Contact lenses: use of therapeutic or refractive contact lenses in either eye within 30 days of study enrolment 9.Concomitant treatments: topical cyclosporine; topical corticosteroids or any other topical medication for the treatment of dry eye in either eye within 30 days before the screening; systemic medications admitted only if at a stable dose for at least 3 months before the screening; systemic or topical hormonal therapies within 3 months before the screening 10.Allergy: ascertained or presumptive hypersensitivity to the active principle and/or ingredients of investigational product or Oculotect® or rescue medication; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study 11.Diseases: uncontrolled systemic diseases including cardiovascular, pulmonary and/or renal diseases, diabetes, hypertension; history of ovarian, breast or uterine cancer or unexplained vaginal bleeding 12.Investigative drug studies: participation in the evaluation of any investigational product or medical device for 30 days before this study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is the evaluation of the clinical efficacy during and at the end of the treatment with RP101 ophthalmic sterile solution or matching placebo (vehicle) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Schirmer test type II (with anaesthesia) |
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E.5.2 | Secondary end point(s) |
The secondary end points are: - Evaluation of the clinical efficacy during and at the end of treatment with RP101 ophthalmic sterile solution or matching placebo (vehicle) - Evaluation of the clinical safety during and at the end of treatment with RP101 ophthalmic sterile solution or matching placebo (vehicle) - evaluation of the PK of serum 17-β-oestradiol after the 1st and the last dose of treatment with RP101 ophthalmic sterile solution (only in the pk stubstudy) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- VAS for ocular tolerability - Symptom Assessment in Dry Eye (SANDE) - Visual acuity (ETDRS chart) - Slit lamp examination (SLE) - Tear film osmolarity - Tear film break up time (TFBUT) - Fundus ophthalmoscopy - Corneal fluorescein staining - Corneal pachymetry - Frequency of instillation (i.e. number of drops instilled daily) of artificial tears (rescue medication) during the treatment phase - Intraocular pressure (IOP) - Treatment-emergent adverse events (TEAEs) - Clinical laboratory assays including haematology, blood chemistry and endocrinology - Vital signs (blood pressure; BP, pulse rate; PR), body weight (BW), physical examinations - 17-β-oestradiol serum concentrations, Cmax, Tmax and AUC0-t
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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 | Yes |
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) | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 study will be considered terminated at the date of the last visit of the last subject or upon completion of any follow-up procedure described in protocol |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |