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

Dry Eye Syndromes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03821415
• Other study ID #: RP101-200
• Status: Completed
• Phase: Phase 2
• Start date: January 18, 2019
• Est. completion date: November 18, 2019

Study information

• Verified date: December 2019
• Source: Redwood Pharma AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: November 18, 2019
• Est. primary completion date: November 18, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Dry Eye Syndromes
• Keratoconjunctivitis Sicca
• Syndrome

Intervention

Drug:
• RP101
17ß-oestradiol-3-phosphate ophthalmic sterile solution

Locations

Country	Name	City	State
Austria	Medical University of Vienna - Department of Clinical Pharmacology	Vienna
Germany	Universitätsmedizin Greifswald, Klinik und Poliklinik für Augenheilkunde	Greifswald
Germany	Universitätsmedizin Mainz Augenklinik und Poliklinik Klinisches	Mainz
Germany	Klinikum rechts der Isar der Technischen Universität München, Anstalt des öffentlichen Rechts Klinik und Poliklinik für Augenheilkunde	München
Hungary	Óbudai Egészség Centrum	Budapest
Hungary	Swan Med Hungary Kft.	Létavértes
Hungary	MacroKlinika	Miskolc
Hungary	Mentaház Magánorvosi Központ	Székesfehérvár

Sponsors (2)

Lead Sponsor	Collaborator
Redwood Pharma AB	Cross Research S.A.

Countries where clinical trial is conducted

Austria,  Germany,  Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Corneal fluorescein staining	The corneal fluorescein staining evaluates cornea and conjunctiva epithelium damage.	From Screening up to 90 days
Secondary	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
Secondary	17-ß-oestradiol serum concentrations	Using a fully validated analytical method.	Day 1 and Day 90