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

Primary Purpose

Dry Eye Syndromes

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RP101
Sponsored by
Redwood Pharma AB
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dry Eye Syndromes focused on measuring Keratoconjunctivitis sicca, Dry Eye Disease, Slow-release, Ophthalmology, Topical Eye Disease

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

  • Medical University of Vienna - Department of Clinical Pharmacology
  • Universitätsmedizin Greifswald, Klinik und Poliklinik für Augenheilkunde
  • Universitätsmedizin Mainz Augenklinik und Poliklinik Klinisches
  • Klinikum rechts der Isar der Technischen Universität München, Anstalt des öffentlichen Rechts Klinik und Poliklinik für Augenheilkunde
  • Óbudai Egészség Centrum
  • Swan Med Hungary Kft.
  • MacroKlinika
  • Mentaház Magánorvosi Központ

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

1 - RP101 0.05%

2 - RP101 0.1% / Placebo

3 - RP101 0.1%

4 - Placebo

Arm Description

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

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

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

RP101 matching placebo, ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days

Outcomes

Primary Outcome Measures

Schirmer's test type II (with anaesthesia)
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)
It will be assigned by the patients using a 100 mm VAS.
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).
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.
Slit lamp examination (SLE)
The SLE will be performed before the instillation of any dilating or anaesthetic eye drops or the fluorescein agent.
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.
Fundus ophthalmoscopy
The fundus examination will include ophthalmoscopic assessments of vitreous, macula, retina and optic nerve head for both eyes.
Corneal fluorescein staining
The corneal fluorescein staining evaluates cornea and conjunctiva epithelium damage.
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.
17-β-oestradiol serum concentrations
Using a fully validated analytical method.

Full Information

First Posted
January 16, 2019
Last Updated
December 19, 2019
Sponsor
Redwood Pharma AB
Collaborators
Cross Research S.A.
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1. Study Identification

Unique Protocol Identification Number
NCT03821415
Brief Title
Effects of RP101 in Post-menopausal Women With Dry Eye Syndrome
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
January 18, 2019 (Actual)
Primary Completion Date
November 18, 2019 (Actual)
Study Completion Date
November 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Redwood Pharma AB
Collaborators
Cross Research S.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Syndromes
Keywords
Keratoconjunctivitis sicca, Dry Eye Disease, Slow-release, Ophthalmology, Topical Eye Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
104 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1 - RP101 0.05%
Arm Type
Experimental
Arm Description
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
Arm Title
2 - RP101 0.1% / Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
3 - RP101 0.1%
Arm Type
Experimental
Arm Description
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
Arm Title
4 - Placebo
Arm Type
Placebo Comparator
Arm Description
RP101 matching placebo, ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days
Intervention Type
Drug
Intervention Name(s)
RP101
Other Intervention Name(s)
17β-oestradiol-3-phosphate
Intervention Description
17β-oestradiol-3-phosphate ophthalmic sterile solution
Primary Outcome Measure Information:
Title
Schirmer's test type II (with anaesthesia)
Description
Schirmer's test uses sterile strips inserted into the eye to measure the basal aqueous tear secretion.
Time Frame
From Screening up to 90 days
Secondary Outcome Measure Information:
Title
Visual analogue scale (VAS) for ocular tolerability (foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, redness, tearing, eyelid swelling and photophobia)
Description
It will be assigned by the patients using a 100 mm VAS.
Time Frame
From Screening up to 90 days
Title
Symptom assessment in Dry Eye (SANDE)
Description
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).
Time Frame
From Screening up to 90 days
Title
Visual acuity assessment using an Early Treatment Diabetic Retinopathy Study [ETDRS] chart
Description
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.
Time Frame
From Screening up to 90 days
Title
Slit lamp examination (SLE)
Description
The SLE will be performed before the instillation of any dilating or anaesthetic eye drops or the fluorescein agent.
Time Frame
From Screening up to 90 days
Title
TFBUT
Description
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.
Time Frame
From Screening up to 90 days
Title
Fundus ophthalmoscopy
Description
The fundus examination will include ophthalmoscopic assessments of vitreous, macula, retina and optic nerve head for both eyes.
Time Frame
From Screening up to 90 days
Title
Corneal fluorescein staining
Description
The corneal fluorescein staining evaluates cornea and conjunctiva epithelium damage.
Time Frame
From Screening up to 90 days
Title
Treatment-emergent Adverse Event (TEAEs)
Description
All adverse events (AEs) derived by spontaneous, unsolicited reports of the subjects, by observation and by routine open questioning will be collected and reported.
Time Frame
From Screening up to 104 days
Title
17-β-oestradiol serum concentrations
Description
Using a fully validated analytical method.
Time Frame
Day 1 and Day 90

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ulf Björklund, MSc Pharm
Organizational Affiliation
Redwood Pharma AB
Official's Role
Study Director
Facility Information:
Facility Name
Medical University of Vienna - Department of Clinical Pharmacology
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Universitätsmedizin Greifswald, Klinik und Poliklinik für Augenheilkunde
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
Universitätsmedizin Mainz Augenklinik und Poliklinik Klinisches
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Klinikum rechts der Isar der Technischen Universität München, Anstalt des öffentlichen Rechts Klinik und Poliklinik für Augenheilkunde
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Óbudai Egészség Centrum
City
Budapest
ZIP/Postal Code
1036
Country
Hungary
Facility Name
Swan Med Hungary Kft.
City
Létavértes
ZIP/Postal Code
4281
Country
Hungary
Facility Name
MacroKlinika
City
Miskolc
ZIP/Postal Code
3526
Country
Hungary
Facility Name
Mentaház Magánorvosi Központ
City
Székesfehérvár
ZIP/Postal Code
8000
Country
Hungary

12. IPD Sharing Statement

Citations:
PubMed Identifier
33710587
Citation
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.
Results Reference
derived

Learn more about this trial

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

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