Safety and Efficacy of Two Different Concentrations (0.5% and 1%) of Progesterone Topical Gel Compared to Placebo in Patients Diagnosed With Moderate to Severe Dry Eye Syndrome

Study Overview
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Brief Summary
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Multicenter, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group, Phase 2 clinical trial. The study objective is to evaluate the safety and efficacy of two different concentrations (0.5% and 1%) of progesterone topical gel compared to placebo, when administered twice a day for 3 months (12 weeks) in patients diagnosed with moderate to severe dry eye syndrome.

Official Title
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A Multicenter, Randomized, Double-Masked, Placebo-Controlled Phase II Study to Evaluate the Safety and Efficacy of Pro-ocular™ 0.5% and 1% in Patients With Dry Eye Syndrome

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Drug: Pro-ocular gel
* Drug: Placebo gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients (male or female) ≥ 18 years of age. Able and willing to provide voluntary written Informed Consent prior to any study related procedure. Patients must be diagnosed with any type of dry eye at least 3 months before screening (Visit 0). Have all the following in the same eye at Visit 0: Fluorescein staining (Cornea) on NEI (National Eye Institute) grading scale > 3 Average Tear Film Break up Time ≤ 5 seconds Schirmer Test (without anesthesia) ≥ 1 and < 10mm Be able and willing to follow instructions, including participation in all study assessments and visits, according to the opinion of the investigator. Exclusion Criteria: Comorbidity with other severe or chronic conditions that in the judgment of the investigator will interfere with study assessment, such as such as glaucoma, active neuronal trigeminal disease, neuralgia. Best corrected visual acuity (BCVA) baseline <20/200. Condition or history other than ocular that, in the opinion of the investigator, may interfere significantly with the patient's participation in the study, such as dementia, psychosis, Parkinson's disease (interference). Patient using a contact ocular lens within 7 days prior to administration of the first dose and not willing to cease using them during all study duration. Female patients who are pregnant, nursing an infant, or planning a pregnancy or lactating at Screening Visit. Females who are of childbearing potential and not taking adequate contraceptive precautions are excluded from the trial. Females of childbearing potential taking acceptable non-hormonal contraceptive precautions can be included (See Note A). Males with partners who are pregnant or lactating or of childbearing potential and are unwilling to use condoms for the duration of the study. A known adverse reaction and/or sensitivity to the study drug or its components. Use of topical ocular cyclosporine, corticosteroids or any other topical anti-inflammatory treatments within 15 days prior to Visit 0 and during all study duration. Routine use (more than twice a week) of a chlorinated swimming pool during the study period Unwilling or unable to cease using during the study period the forbidden medications: Any topical ocular ointments or gels Topical and systemic glaucoma therapies Systemic drugs with anticholinergic activity: anticonvulsants, antihistamines, antipsychotics, antidepressants, antimuscarinics, anti-Parkinson agents, cardiovascular agents (disopyramide), gastrointestinal agents, muscle relaxants, respiratory medications (pseudoephedrine, theophylline) Lipidic artificial tears and artificial tears with preservative. Unwilling to cease the use of sunscreen on the forehead or eye area during the study period. Habitual cigarette smokers (tobacco, vapor cigarettes, marijuana), smoking more than 4 cigarettes per day. Participation in another clinical study at the same time as the present and within 30 days prior to Visit 0.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Allocation Ratio = 1:1:1
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pro-ocular™ 1% Progesterone EP topical gel<br>Multidose formulation despensing unit doses of 0.07 g of topical gel containing 0.7 mg of progesterone | Drug: Pro-ocular gel<br>* Topical gel in multidose formulation to be applied laterally to the forehead twice a day, morning and night for 3 months<br>|
| Experimental: Pro-ocular™ 0.5% Progesterone EP topical gel<br>Multidose formulation despensing unit doses of 0.07 g of topical gel containing 0.35 mg of progesterone | Drug: Pro-ocular gel<br>* Topical gel in multidose formulation to be applied laterally to the forehead twice a day, morning and night for 3 months<br>|
| Placebo Comparator: Placebo topical gel<br>Multidose formulation identical in appearance to Experimental Products despensing unit doses of 0.07 g of topical gel containing 0 mg of progesterone | Drug: Placebo gel<br>* Topical gel in multidose formulation to be applied laterally to the forehead twice a day, morning and night for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal Fluorescein Staining | Mean change from baseline (Visit 1 pre-dose) in corneal fluorescein staining assessed by NEI scale at Week 12 (Day 84) (with Last Observation Carried Forward (LOCF) imputation) | Week 12 (Day 84) (with Last Observation Carried Forward (LOCF) imputation) | 
| SANDE questionnaire | Mean change from baseline (Visit 1 pre-dose) in sum of frequency and intensity of dryness/irritation patient feeling assessed by SANDE questionnaire at Week 12 (Day 84) (with LOCF imputation) | Week 12 (Day 84) (with Last Observation Carried Forward (LOCF) imputation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal fluorescein staining | Mean change from baseline (Visit 1 pre-dose) in corneal fluorescein staining assessed by NEI scale at Week 12 (Day 84). | Week 12 (Day 84) | 
| SANDE questionnaire | Mean change from baseline (Visit 1 pre-dose) in sum of frequency and intensity of dryness/irritation patient feeling assessed by SANDE questionnaire at Week 12 (Day 84). | Week 12 (Day 84) | 
| Conjunctival fluorescein staining | Mean change from baseline (Visit 1 pre-dose) in conjunctival fluorescein staining assessed by NEI scale at Week 12 (Day 84) (with LOCF imputation). | Week 12 (Day 84) (with Last Observation Carried Forward (LOCF) imputation) | 
| Conjunctival fluorescein staining | Mean change from baseline (Visit 1 pre-dose) in conjunctival fluorescein staining assessed by NEI scale at Week 12 (Day 84). | Week 12 (Day 84) | 
| Corneal fluorescein staining | Mean change from baseline (Visit 1 pre-dose) in corneal fluorescein staining assessed by NEI scale at Week 2, 4, 8 (Day 14, 28, 56) as intermediate study visits. | Week 2, 4, 8 (Day 14, 28, 56) | 
| SANDE questionnaire | Mean change from baseline (Visit 1 pre-dose) in sum of frequency and intensity of dryness/irritation patient feeling assessed by SANDE questionnaire at Week 2, 4, 8, 16 (Day 14, 28, 56,114) as intermediate study visits. | Week 2, 4, 8, 16 (Day 14, 28, 56,114) | 
| Conjunctival fluorescein staining | Mean change from baseline (Visit 1 pre-dose) in conjunctival fluorescein staining assessed by NEI scale at Week 2, 4, 8 (Day 14, 28, 56) as intermediate study visits. | Week 2, 4, 8 (Day 14, 28, 56) | 
| Non-Invasive Keratograph Tear Film Break Up (NIKBUT) Time (NIKBUT) | Mean change from baseline (Visit 1 pre-dose) in Non-Invasive Keratograph Tear Film Break Up Time (NIKBUT) at each applicable post-baseline visit [Week 2, 4, 8, 12 (Day 14, 28, 56, 84)]. | Week 2, 4, 8, 12 (Day 14, 28, 56, 84) | 
| Fluorescein Tear Film Break Up Time (TBUT) | Mean change from baseline (Visit 1 pre-dose) in Fluorescein Tear Film Break Up Time (TBUT) at Week 12 (Day 84). | Week 12 (Day 84) | 
| Tear meniscus height (TMH) | Mean change from baseline (Visit 1 pre-dose) in Tear meniscus height (TMH) at each applicable post-baseline visit [Week 2, 4, 8, 12 (Day 14, 28, 56, 84)]. | Week 2, 4, 8, 12 (Day 14, 28, 56, 84)] | 
| Schirmer test | Mean change from baseline (Visit 0 Screening) in Schirmer test at Week 4 (Day 28) and at Week 12 (Day 84). | Week 4 (Day 28) and Week 12 (Day 84) | 
| Dry Eye-Related Quality-of-Life (DEQS) questionnaire | Impact of dry eye on quality of life by using Dry Eye-Related Quality-of-Life (DEQS) questionnaire. | Each applicable post baseline visit | 
| Visual Analogue Scale | Absolute score of each symptom item in Visual Analogue Scale to each post baseline visit. | Each applicable post baseline visit | 
| Visual Analogue Scale | Mean change from baseline (Visit 1 pre-dose) in Visual Analogue Scale 7 symptoms items to each applicable post-baseline visit [Week 2, 4, 8, 12 (Day 14, 28, 56, 84)]. | Week 2, 4, 8, 12 (Day 14, 28, 56, 84) | 
| Corneal Sensitivity | Mean change from baseline (Visit 1 pre-dose) in Corneal Sensitivity to each applicable postbaseline visit [Week 4, 12 (Day 28, 84)]. | Week 4, 12 (Day 28, 84) | 
| Slit Lamp Examination | Mean change from baseline (Visit 0 Screening) in Slit Lamp Examination to each applicable post-baseline visit [Week 2, 4, 8, 12 (Day 14, 28, 56, 84)]. | Week 2, 4, 8, 12 (Day 14, 28, 56, 84) |