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

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

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

Study Overview

• Status: Completed
• Conditions: Dry Eye Syndromes
• Intervention / Treatment: Drug: RP101

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna - Department of Clinical Pharmacology
• Germany
  • Greifswald, Germany, 17475
    • Universitätsmedizin Greifswald, Klinik und Poliklinik für Augenheilkunde
  • Mainz, Germany, 55131
    • Universitätsmedizin Mainz Augenklinik und Poliklinik Klinisches
  • München, Germany, 81675
    • Klinikum rechts der Isar der Technischen Universität München, Anstalt des öffentlichen Rechts Klinik und Poliklinik für Augenheilkunde
• Hungary
  • Budapest, Hungary, 1036
    • Óbudai Egészség Centrum
  • Létavértes, Hungary, 4281
    • Swan Med Hungary Kft.
  • Miskolc, Hungary, 3526
    • MacroKlinika
  • Székesfehérvár, Hungary, 8000
    • Mentahaz Maganorvosi Kozpont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 - RP101 0.05%; 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; 17β-oestradiol-3-phosphate ophthalmic sterile solution; Other Names: 17β-oestradiol-3-phosphate
Experimental: 2 - RP101 0.1% / Placebo; 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; 17β-oestradiol-3-phosphate ophthalmic sterile solution; Other Names: 17β-oestradiol-3-phosphate
Experimental: 3 - RP101 0.1%; 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; 17β-oestradiol-3-phosphate ophthalmic sterile solution; Other Names: 17β-oestradiol-3-phosphate
Placebo Comparator: 4 - Placebo; RP101 matching placebo, ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days	Drug: RP101; 17β-oestradiol-3-phosphate ophthalmic sterile solution; Other Names: 17β-oestradiol-3-phosphate

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Redwood Pharma AB
• Collaborators: Cross Research S.A.
• Investigators: Study Director: Ulf Björklund, MSc Pharm, Redwood Pharma AB

Publications and helpful links

General Publications

• Schmidl D, Szalai L, Kiss OG, Schmetterer L, Garhofer G. A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Masked Trial of a Topical Estradiol Ophthalmic Formulation in Postmenopausal Women with Moderate-to-Severe Dry Eye Disease. Adv Ther. 2021 Apr;38(4):1975-1986. doi: 10.1007/s12325-021-01680-3. Epub 2021 Mar 12.

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2019
• Primary Completion (Actual): November 18, 2019
• Study Completion (Actual): November 18, 2019

Study Registration Dates

• First Submitted: January 16, 2019
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): December 20, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Ophthalmology; Dry Eye Disease; Keratoconjunctivitis sicca; Slow-release; Topical Eye Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Disease; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Syndrome; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: RP101-200

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No