Dry Eye SyndromesPhase 2NCT03821415
Effects of RP101 in Post-menopausal Women With Dry Eye Syndrome
A Phase 2 study testing RP101 in people with Dry Eye Syndromes, run by Redwood Pharma AB at 8 sites in 3 countries.
Trial summary
The main purpose of this study is to establish whether RP101 can reduce symptoms of dry eye syndrome in post-menopausal women. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Dry Eye Syndromes
- What is being tested?
- RP101
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 8 sitesin 3 countries
- Study dates
- 18 Jan 2019to 18 Nov 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
Hungary4 sites
Óbudai Egészség Centrum
Budapest, 1036
Swan Med Hungary Kft.
Létavértes, 4281
MacroKlinika
Miskolc, 3526
Mentaház Magánorvosi Központ
Székesfehérvár, 8000
Germany3 sites
Universitätsmedizin Greifswald, Klinik und Poliklinik für Augenheilkunde
Greifswald, 17475
Universitätsmedizin Mainz Augenklinik und Poliklinik Klinisches
Mainz, 55131
Klinikum rechts der Isar der Technischen Universität München, Anstalt des öffentlichen Rechts Klinik und Poliklinik für Augenheilkunde
München, 81675
Austria1 site
Medical University of Vienna - Department of Clinical Pharmacology
Vienna, 1090
About this study
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
The main purpose of this study is to establish whether RP101 can reduce symptoms of dry eye syndrome in post-menopausal women.
Read the 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).
- Conditions
- Dry Eye Syndromes
- Being tested
- RP101
- Keywords
- Keratoconjunctivitis sicca, Dry Eye Disease, Slow-release, Ophthalmology, Topical Eye Disease
- Medical subject headings
- Dry Eye Syndromes, Keratoconjunctivitis Sicca
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP101Drug
Also called 17β-oestradiol-3-phosphate
17β-oestradiol-3-phosphate ophthalmic sterile solution
| Study group | Role | What they receive |
|---|---|---|
| 1 - RP101 0.05% | Experimental | 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 Receives: Drug: RP101 |
| 2 - RP101 0.1% / Placebo | Experimental | 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 Receives: Drug: RP101 |
| 3 - RP101 0.1% | Experimental | 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 Receives: Drug: RP101 |
| 4 - Placebo | Placebo comparator | RP101 matching placebo, ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days Receives: Drug: RP101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Schirmer's test type II (with anaesthesia)
Schirmer's test uses sterile strips inserted into the eye to measure the basal aqueous tear secretion.
Measured: From Screening up to 90 days
Secondary outcomes (9)
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Screening up to 90 days
Corneal fluorescein staining
The corneal fluorescein staining evaluates cornea and conjunctiva epithelium damage.
Measured: 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.
Measured: From Screening up to 104 days
17-β-oestradiol serum concentrations
Using a fully validated analytical method.
Measured: Day 1 and Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2019
- Study start18 Jan 2019
- Primary completion18 Nov 2019
- Study completion18 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dry Eye SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Redwood Pharma AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A.
- Responsible party
- Sponsor
- Investigators
- Ulf Björklund, MSc Pharm, Study director, Redwood Pharma AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03821415
- Sponsor's protocol ID
- RP101-200
- Status last verified
- Dec 2019
- First submitted
- 16 Jan 2019
- Last updated
- 20 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 33710587
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03821415
- Acronym / sponsor ID
- RP101-200
- Conditions
- Dry Eye Syndromes
- Keywords
- Keratoconjunctivitis sicca, Dry Eye Disease, Slow-release, Ophthalmology, Topical Eye Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Redwood Pharma ABIndustry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A.
- Study start
- 18 Jan 2019 (actual)
- Primary completion
- 18 Nov 2019 (actual)
- Study completion
- 18 Nov 2019 (actual)
- First posted
- 29 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study
| Arm | Type | Receives |
|---|---|---|
| 1 - RP101 0.05% | Experimental | Drug: RP101RP101 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 |
| 2 - RP101 0.1% / Placebo | Experimental | Drug: RP101RP101 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 |
| 3 - RP101 0.1% | Experimental | Drug: RP101RP101 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 |
| 4 - Placebo | Placebo comparator | Drug: RP101RP101 matching placebo, ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RP101Also: 17β-oestradiol-3-phosphate17β-oestradiol-3-phosphate ophthalmic sterile solution | Drug | 1 - RP101 0.05%, 2 - RP101 0.1% / Placebo, 3 - RP101 0.1%, 4 - Placebo |
Primary outcome
Schirmer's test type II (with anaesthesia)
Time frame: From Screening up to 90 days
Schirmer's test uses sterile strips inserted into the eye to measure the basal aqueous tear secretion.
9 secondary outcomes
Visual analogue scale (VAS) for ocular tolerability (foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, redness, tearing, eyelid swelling and photophobia)
Time frame: From Screening up to 90 days
Symptom assessment in Dry Eye (SANDE)
Time frame: From Screening up to 90 days
Visual acuity assessment using an Early Treatment Diabetic Retinopathy Study [ETDRS] chart
Time frame: From Screening up to 90 days
Slit lamp examination (SLE)
Time frame: From Screening up to 90 days
TFBUT
Time frame: From Screening up to 90 days
Fundus ophthalmoscopy
Time frame: From Screening up to 90 days
Corneal fluorescein staining
Time frame: From Screening up to 90 days
Treatment-emergent Adverse Event (TEAEs)
Time frame: From Screening up to 104 days
17-β-oestradiol serum concentrations
Time frame: Day 1 and Day 90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2019.
- Derived from this study: PubMed 33710587Schmidl 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ulf Björklund, MSc Pharm study director
Redwood Pharma AB
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RP101 in people with Dry Eye Syndromes, run by Redwood Pharma AB at 8 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Hungary, Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Schirmer's test type II (with anaesthesia) (time frame: From Screening up to 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03821415, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2019.