A Phase II, multicentre, randomised, placebo-controlled, double-masked trial of RP101 ophthalmic formulation versus vehicle in post-menopausal women with moderate to severe dry eye syndrome

Phase 1

• Conditions: moderate or severe dry eye syndrome; MedDRA version: 20.0 Level: PT Classification code 10013774 Term: Dry eye System Organ Class: 10015919 - Eye disorders; Therapeutic area: Diseases [C] - Eye Diseases [C11]

• Registration Number: EUCTR2017-005160-18-AT
• Lead Sponsor: Redwood Pharma AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-06-07
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 100

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

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 (in particular, history of or active deep vein thrombosis or active or recent thromboembolism disease), pulmonary (in particular history of or active pulmonary embolism), hepatic and/or renal diseases or dysfunctions, diabetes, hypertension; known, suspected or history of ovarian, breast or uterine cancer or known or suspected oestrogen-dependent neoplasia or unexplained vaginal or genital bleeding; risk of endometrial hyperplasia
12.Investigative drug studies: participation in the evaluation of any investigational product or medical device for 30 days before this study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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;<br> Secondary Objective: The secondary objectives of the study are:<br> - to evaluate the safety and tolerability of the treatment<br> - to evaluate as exploratory variables tear film osmolarity and corneal pachymetry in specific substudies<br> - to evaluate the pharmacokinetics (PK) of serum 17-ß-oestradiol after the 1st and the last dose (only PK substudy)<br> ;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);Timepoint(s) of evaluation of this end point: Schirmer test type II (with anaesthesia)