Effects of RP101 in Post-menopausal Women With Dry Eye Syndrome

Study Overview
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Brief Summary
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The main purpose of this study is to establish whether RP101 can reduce symptoms of dry eye syndrome in post-menopausal women.

Detailed Description
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Redwood Pharma is developing the novel ophthalmic product RP101 containing the known active substance 17β-oestradiol-3-phosphate and based upon the drug delivery platform IntelliGel which controls the active substance release. The novel formulation is planned to meet the still unmet medical need of an efficacious treatment against chronic dry eye in postmenopausal women. The efficacy of the novel formulation RP101 will be investigated for the first time in the present multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study in women post-menopausal for at least 3 years presenting with symptoms specific for dry eye syndrome of moderate to severe intensity. The planned study will be conducted in Austria, Germany and Hungary. The primary objective of the study is to establish the effective dose/dose regimen of RP101 in these patients applying RP101 ophthalmic sterile solution or matching placebo (vehicle) once (q.d.) or twice a day (b.i.d.) for 3 months. One hundred (100) patients will be enrolled in this study. The subjects will be randomly assigned (1:1:1:1) to a treatment group and will receive one of the treatments for 90 consecutive days. Evaluation of the clinical efficacy during and at the end of the treatment will be done on the basis of the Schirmer's test type II (with anaesthesia). The secondary objectives of the study are: to evaluate the safety and tolerability of the treatment to evaluate the pharmacokinetics (PK) of serum 17β-oestradiol after the 1st and the last dose (only PK substudy).

Official Title
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A Phase II, Multicentre, Randomised, Placebo-controlled, Doublemasked Trial of RP101 Ophthalmic Formulation Versus Vehicle in Post-menopausal Women With Moderate to Severe Dry Eye Syndrome

Conditions
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Dry Eye Syndromes

Intervention / Treatment
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* Drug: RP101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent: signed written informed consent before inclusion in the study Sex and menopause: postmenopausal women; postmenopausal condition defined as final menstrual period at least 3 years before the screening Dry eye syndrome: patients with moderate to severe dry eye syndrome Tear film breakup time: TFBUT ≤ 10 sec in the worse eye (study eye) Visual acuity: corrected visual acuity ≥ 20/200 in each eye 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 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 Exclusion Criteria: Meibomian gland dysfunction: severe Meibomian gland dysfunction defined as lid deformity, marked lid margin hyperaemia or severe Meibomian gland loss Ophthalmic treatment: current use of topical ophthalmic medications other than ocular lubricants or artificial tears within 30 days before the screening 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 Ophthalmic diseases: severe forms of ophthalmic surface diseases e.g. ocular pemphigoid, Sjögren's disease, exposure keratitis 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 Diseases: uncontrolled systemic diseases including cardiovascular, pulmonary and/or renal diseases, diabetes, hypertension; history of ovarian, breast or uterine cancer or unexplained vaginal bleeding Investigative drug studies: participation in the evaluation of any investigational product or medical device for 30 days before this study
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 - RP101 0.05%<br>RP101 0.05% (w/w) 17β-oestradiol-3-phosphate ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days | Drug: RP101<br>* 17β-oestradiol-3-phosphate ophthalmic sterile solution<br>* Other names: 17β-oestradiol-3-phosphate;|
| Experimental: 2 - RP101 0.1% / Placebo<br>RP101 0.1% (w/w) 17β-oestradiol-3-phosphate ophthalmic sterile solution, one drop each eye in the morning (q.d.) followed by one drop of placebo each eye in the evening for 90 consecutive days | Drug: RP101<br>* 17β-oestradiol-3-phosphate ophthalmic sterile solution<br>* Other names: 17β-oestradiol-3-phosphate;|
| Experimental: 3 - RP101 0.1%<br>RP101 0.1% (w/w) 17β-oestradiol-3-phosphate ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days | Drug: RP101<br>* 17β-oestradiol-3-phosphate ophthalmic sterile solution<br>* Other names: 17β-oestradiol-3-phosphate;|
| Placebo Comparator: 4 - Placebo<br>RP101 matching placebo, ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days | Drug: RP101<br>* 17β-oestradiol-3-phosphate ophthalmic sterile solution<br>* Other names: 17β-oestradiol-3-phosphate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Schirmer's test type II (with anaesthesia) | Schirmer's test uses sterile strips inserted into the eye to measure the basal aqueous tear secretion. | From Screening up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analogue scale (VAS) for ocular tolerability (foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, redness, tearing, eyelid swelling and photophobia) | It will be assigned by the patients using a 100 mm VAS. | From Screening up to 90 days | 
| Symptom assessment in Dry Eye (SANDE) | The patient symptoms of ocular dryness and/or irritation will be quantified on a Visual Analogue Scale (VAS) 0-100 mm based on two questions that inquire about both severity and frequency of symptoms. The patients will evaluate their symptoms on the VAS scale giving the value they are feeling from none (0 mm) to an extreme value (100 mm). | From Screening up to 90 days | 
| Visual acuity assessment using an Early Treatment Diabetic Retinopathy Study [ETDRS] chart | Best correction will be determined by careful refraction using a retroilluminated ETDRS 4 meter distance acuity chart. The correct number of letters read by the patient is recorded and evaluated. | From Screening up to 90 days | 
| Slit lamp examination (SLE) | The SLE will be performed before the instillation of any dilating or anaesthetic eye drops or the fluorescein agent. | From Screening up to 90 days | 
| TFBUT | Tear film break up time (TFBUT) will be measured by determining the time to tear break-up after instillation of sodium fluorescein solution into the inferior conjunctival culde-sac of each eye. | From Screening up to 90 days | 
| Fundus ophthalmoscopy | The fundus examination will include ophthalmoscopic assessments of vitreous, macula, retina and optic nerve head for both eyes. | From Screening up to 90 days | 
| Corneal fluorescein staining | The corneal fluorescein staining evaluates cornea and conjunctiva epithelium damage. | From Screening up to 90 days | 
| Treatment-emergent Adverse Event (TEAEs) | All adverse events (AEs) derived by spontaneous, unsolicited reports of the subjects, by observation and by routine open questioning will be collected and reported. | From Screening up to 104 days | 
| 17-β-oestradiol serum concentrations | Using a fully validated analytical method. | Day 1 and Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ophthalmology, Topical Eye Disease, Keratoconjunctivitis sicca, Dry Eye Disease, Slow-release