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

Sponsor

Redwood Pharma AB (Industry)

Overall Status

Completed

CT.gov ID

NCT03821415

Collaborator

Cross Research S.A. (Industry)

104

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes	Drug: RP101	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II studyMulticentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 18, 2019

Actual Primary Completion Date :

Nov 18, 2019

Actual Study Completion Date :

Nov 18, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Schirmer's test type II (with anaesthesia) [From Screening up to 90 days]
Schirmer's test uses sterile strips inserted into the eye to measure the basal aqueous tear secretion.

Secondary Outcome Measures

Visual analogue scale (VAS) for ocular tolerability (foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, redness, tearing, eyelid swelling and photophobia) [From Screening up to 90 days]
It will be assigned by the patients using a 100 mm VAS.
Symptom assessment in Dry Eye (SANDE) [From Screening up to 90 days]
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).
Visual acuity assessment using an Early Treatment Diabetic Retinopathy Study [ETDRS] chart [From Screening up to 90 days]
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.
Slit lamp examination (SLE) [From Screening up to 90 days]
The SLE will be performed before the instillation of any dilating or anaesthetic eye drops or the fluorescein agent.
TFBUT [From Screening up to 90 days]
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.
Fundus ophthalmoscopy [From Screening up to 90 days]
The fundus examination will include ophthalmoscopic assessments of vitreous, macula, retina and optic nerve head for both eyes.
Corneal fluorescein staining [From Screening up to 90 days]
The corneal fluorescein staining evaluates cornea and conjunctiva epithelium damage.
Treatment-emergent Adverse Event (TEAEs) [From Screening up to 104 days]
All adverse events (AEs) derived by spontaneous, unsolicited reports of the subjects, by observation and by routine open questioning will be collected and reported.
17-β-oestradiol serum concentrations [Day 1 and Day 90]
Using a fully validated analytical method.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Medical University of Vienna - Department of Clinical Pharmacology	Vienna	Austria	1090
2	Universitätsmedizin Greifswald, Klinik und Poliklinik für Augenheilkunde	Greifswald	Germany	17475
3	Universitätsmedizin Mainz Augenklinik und Poliklinik Klinisches	Mainz	Germany	55131
4	Klinikum rechts der Isar der Technischen Universität München, Anstalt des öffentlichen Rechts Klinik und Poliklinik für Augenheilkunde	München	Germany	81675
5	Óbudai Egészség Centrum	Budapest	Hungary	1036
6	Swan Med Hungary Kft.	Létavértes	Hungary	4281
7	MacroKlinika	Miskolc	Hungary	3526
8	Mentaház Magánorvosi Központ	Székesfehérvár	Hungary	8000