<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03821415</url>
  </required_header>
  <id_info>
    <org_study_id>RP101-200</org_study_id>
    <nct_id>NCT03821415</nct_id>
  </id_info>
  <brief_title>Effects of RP101 in Post-menopausal Women With Dry Eye Syndrome</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Redwood Pharma AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cross Research S.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Redwood Pharma AB</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to establish whether RP101 can reduce symptoms of dry eye&#xD;
      syndrome in post-menopausal women.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Redwood Pharma is developing the novel ophthalmic product RP101 containing the known active&#xD;
      substance 17β-oestradiol-3-phosphate and based upon the drug delivery platform IntelliGel&#xD;
      which controls the active substance release. The novel formulation is planned to meet the&#xD;
      still unmet medical need of an efficacious treatment against chronic dry eye in&#xD;
      postmenopausal women.&#xD;
&#xD;
      The efficacy of the novel formulation RP101 will be investigated for the first time in the&#xD;
      present multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II&#xD;
      study in women post-menopausal for at least 3 years presenting with symptoms specific for dry&#xD;
      eye syndrome of moderate to severe intensity.&#xD;
&#xD;
      The planned study will be conducted in Austria, Germany and Hungary. The primary objective of&#xD;
      the study is to establish the effective dose/dose regimen of RP101 in these patients applying&#xD;
      RP101 ophthalmic sterile solution or matching placebo (vehicle) once (q.d.) or twice a day&#xD;
      (b.i.d.) for 3 months. One hundred (100) patients will be enrolled in this study. The&#xD;
      subjects will be randomly assigned (1:1:1:1) to a treatment group and will receive one of the&#xD;
      treatments for 90 consecutive days.&#xD;
&#xD;
      Evaluation of the clinical efficacy during and at the end of the treatment will be done on&#xD;
      the basis of the Schirmer's test type II (with anaesthesia).&#xD;
&#xD;
      The secondary objectives of the study are:&#xD;
&#xD;
        -  to evaluate the safety and tolerability of the treatment&#xD;
&#xD;
        -  to evaluate the pharmacokinetics (PK) of serum 17β-oestradiol after the 1st and the last&#xD;
           dose (only PK substudy).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 18, 2019</start_date>
  <completion_date type="Actual">November 18, 2019</completion_date>
  <primary_completion_date type="Actual">November 18, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Schirmer's test type II (with anaesthesia)</measure>
    <time_frame>From Screening up to 90 days</time_frame>
    <description>Schirmer's test uses sterile strips inserted into the eye to measure the basal aqueous tear secretion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual analogue scale (VAS) for ocular tolerability (foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, redness, tearing, eyelid swelling and photophobia)</measure>
    <time_frame>From Screening up to 90 days</time_frame>
    <description>It will be assigned by the patients using a 100 mm VAS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptom assessment in Dry Eye (SANDE)</measure>
    <time_frame>From Screening up to 90 days</time_frame>
    <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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual acuity assessment using an Early Treatment Diabetic Retinopathy Study [ETDRS] chart</measure>
    <time_frame>From Screening up to 90 days</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Slit lamp examination (SLE)</measure>
    <time_frame>From Screening up to 90 days</time_frame>
    <description>The SLE will be performed before the instillation of any dilating or anaesthetic eye drops or the fluorescein agent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFBUT</measure>
    <time_frame>From Screening up to 90 days</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fundus ophthalmoscopy</measure>
    <time_frame>From Screening up to 90 days</time_frame>
    <description>The fundus examination will include ophthalmoscopic assessments of vitreous, macula, retina and optic nerve head for both eyes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corneal fluorescein staining</measure>
    <time_frame>From Screening up to 90 days</time_frame>
    <description>The corneal fluorescein staining evaluates cornea and conjunctiva epithelium damage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-emergent Adverse Event (TEAEs)</measure>
    <time_frame>From Screening up to 104 days</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>17-β-oestradiol serum concentrations</measure>
    <time_frame>Day 1 and Day 90</time_frame>
    <description>Using a fully validated analytical method.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">104</enrollment>
  <condition>Dry Eye Syndromes</condition>
  <arm_group>
    <arm_group_label>1 - RP101 0.05%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2 - RP101 0.1% / Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3 - RP101 0.1%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4 - Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>RP101 matching placebo, ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RP101</intervention_name>
    <description>17β-oestradiol-3-phosphate ophthalmic sterile solution</description>
    <arm_group_label>1 - RP101 0.05%</arm_group_label>
    <arm_group_label>2 - RP101 0.1% / Placebo</arm_group_label>
    <arm_group_label>3 - RP101 0.1%</arm_group_label>
    <arm_group_label>4 - Placebo</arm_group_label>
    <other_name>17β-oestradiol-3-phosphate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent: signed written informed consent before inclusion in the study&#xD;
&#xD;
          -  Sex and menopause: postmenopausal women; postmenopausal condition defined as final&#xD;
             menstrual period at least 3 years before the screening&#xD;
&#xD;
          -  Dry eye syndrome: patients with moderate to severe dry eye syndrome&#xD;
&#xD;
          -  Tear film breakup time: TFBUT ≤ 10 sec in the worse eye (study eye)&#xD;
&#xD;
          -  Visual acuity: corrected visual acuity ≥ 20/200 in each eye&#xD;
&#xD;
          -  Symptoms: at least 2 of the typical dry eye syndrome symptoms since at least 3 months&#xD;
             before the screening: foreign body sensation, burning/stinging, redness, tearing,&#xD;
             pain, itching, blurred vision, photophobia, eyelid swelling, moisture and mucous&#xD;
             discharge&#xD;
&#xD;
          -  Full comprehension: ability to comprehend the full nature and purpose of the study,&#xD;
             including possible risks and side effects; ability to co-operate with the investigator&#xD;
             and to comply with the requirements of the entire study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Meibomian gland dysfunction: severe Meibomian gland dysfunction defined as lid&#xD;
             deformity, marked lid margin hyperaemia or severe Meibomian gland loss&#xD;
&#xD;
          -  Ophthalmic treatment: current use of topical ophthalmic medications other than ocular&#xD;
             lubricants or artificial tears within 30 days before the screening&#xD;
&#xD;
          -  Ocular infection and inflammation: presence of any bacterial or viral or fungal&#xD;
             infection in either eye or active inflammation not related to dry eye disease (i.e.&#xD;
             follicular conjunctivitis, iris or preauricular adenopathy) in either eye&#xD;
&#xD;
          -  Ophthalmic diseases: severe forms of ophthalmic surface diseases e.g. ocular&#xD;
             pemphigoid, Sjögren's disease, exposure keratitis&#xD;
&#xD;
          -  Ophthalmic surgery: history of ophthalmic surgery or trauma in the last 6 months;&#xD;
             history of laser-assisted in situ keratomileusis (LASIK) in the previous 12 months&#xD;
&#xD;
          -  Diseases: uncontrolled systemic diseases including cardiovascular, pulmonary and/or&#xD;
             renal diseases, diabetes, hypertension; history of ovarian, breast or uterine cancer&#xD;
             or unexplained vaginal bleeding&#xD;
&#xD;
          -  Investigative drug studies: participation in the evaluation of any investigational&#xD;
             product or medical device for 30 days before this study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ulf Björklund, MSc Pharm</last_name>
    <role>Study Director</role>
    <affiliation>Redwood Pharma AB</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Vienna - Department of Clinical Pharmacology</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Greifswald, Klinik und Poliklinik für Augenheilkunde</name>
      <address>
        <city>Greifswald</city>
        <zip>17475</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Mainz Augenklinik und Poliklinik Klinisches</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum rechts der Isar der Technischen Universität München, Anstalt des öffentlichen Rechts Klinik und Poliklinik für Augenheilkunde</name>
      <address>
        <city>München</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Óbudai Egészség Centrum</name>
      <address>
        <city>Budapest</city>
        <zip>1036</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swan Med Hungary Kft.</name>
      <address>
        <city>Létavértes</city>
        <zip>4281</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MacroKlinika</name>
      <address>
        <city>Miskolc</city>
        <zip>3526</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mentaház Magánorvosi Központ</name>
      <address>
        <city>Székesfehérvár</city>
        <zip>8000</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Germany</country>
    <country>Hungary</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>December 19, 2019</last_update_submitted>
  <last_update_submitted_qc>December 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Keratoconjunctivitis sicca</keyword>
  <keyword>Dry Eye Disease</keyword>
  <keyword>Slow-release</keyword>
  <keyword>Ophthalmology</keyword>
  <keyword>Topical Eye Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estradiol</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03821415
org study id: RP101-200
nct id: NCT03821415
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main purpose of this study is to establish whether RP101 can reduce symptoms of dry eye
      syndrome in post-menopausal women.
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).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Schirmer's test type II (with anaesthesia)
time frame: From Screening up to 90 days
description: Schirmer's test uses sterile strips inserted into the eye to measure the basal aqueous tear secretion.
measure: 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
description: It will be assigned by the patients using a 100 mm VAS.
measure: Symptom assessment in Dry Eye (SANDE)
time frame: From Screening up to 90 days
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).
measure: Visual acuity assessment using an Early Treatment Diabetic Retinopathy Study [ETDRS] chart
time frame: From Screening up to 90 days
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.
measure: Slit lamp examination (SLE)
time frame: From Screening up to 90 days
description: The SLE will be performed before the instillation of any dilating or anaesthetic eye drops or the fluorescein agent.
measure: TFBUT
time frame: From Screening up to 90 days
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.
measure: Fundus ophthalmoscopy
time frame: From Screening up to 90 days
description: The fundus examination will include ophthalmoscopic assessments of vitreous, macula, retina and optic nerve head for both eyes.
measure: Corneal fluorescein staining
time frame: From Screening up to 90 days
description: The corneal fluorescein staining evaluates cornea and conjunctiva epithelium damage.
measure: Treatment-emergent Adverse Event (TEAEs)
time frame: From Screening up to 104 days
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.
measure: 17-β-oestradiol serum concentrations
time frame: Day 1 and Day 90
description: Using a fully validated analytical method.
arm group label: 1 - RP101 0.05%
arm group type: Experimental
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 group label: 2 - RP101 0.1% / Placebo
arm group type: Experimental
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 group label: 3 - RP101 0.1%
arm group type: Experimental
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 group label: 4 - Placebo
arm group type: Placebo Comparator
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: RP101
description: 17β-oestradiol-3-phosphate ophthalmic sterile solution
arm group label: 1 - RP101 0.05%
arm group label: 2 - RP101 0.1% / Placebo
arm group label: 3 - RP101 0.1%
arm group label: 4 - Placebo
other name: 17β-oestradiol-3-phosphate
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Ulf Björklund, MSc Pharm
role: Study Director
affiliation: Redwood Pharma AB
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Germany
country: Hungary
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Syndrome
mesh term: Estradiol