Efficacy and Tolerability of an Innovative Formulation of BAK-free Latanoprost

Study Overview
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Brief Summary
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This study evaluates the efficacy and tolerability of a new formulation of latanoprost without Benzalkonium Chloride (BAK-free). Patients with open-angle glaucoma who were using BAK-containing latanoprost ophthalmic solution for ≥6 months, switched to BAK-free latanoprost ophthalmic emulsion.

Detailed Description
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Latanoprost is a prostaglandin F2alfa analogue that increases the uveoscleral outflow of aqueous humor, resulting in a intraocular pressure (IOP) reduction. Benzalkonium chloride (BAK) is usually employed in formulations of prostaglandin analogues due to its dual action of preservative and adjuvant in the formulation. However, this preservative has known toxic effects on the ocular surface, causing ocular dryness and discomfort on long-term use. Benzalkonium Chloride-free (BAK-free)Latanoprost is a new formulation approved for the use in patients with primary open angle glaucoma /ocular hypertension. In this study, patients that were using BAK-containing latanoprost for ≥6 months, switched to a new formulation of BAK-free latanoprost ophthalmic emulsion to evaluate its hypotensive action and quantify the changes in ocular surface parameters.

Official Title
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Multicentric Study to Evaluate the Efficacy and Tolerability of an Innovative Formulation of Benzalkonium Chloride-free Latanoprost in Patients With Primary Open-Angle Glaucoma

Conditions
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Primary Open-angle Glaucoma

Intervention / Treatment
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* Drug: Latanoprost Ophthalmic Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged ≥ 18 years Diagnosed with primary open-angle glaucoma or pseudoexfoliative glaucoma. Receiving containing-BAK latanoprost as monotherapy for at least 6 months Pachymetry between 520 and 580 microns Informed consent given Exclusion Criteria: History of allergic hypersensitivity or poor tolerance to latanoprost or any components of the formula Angle closure glaucoma or secondary glaucoma History of recent previous glaucoma surgery or trabeculoplasty (less than 1 year of surgery) History of cataract surgery during the last 6 months History of uveitis or intraocular inflammation Corneal alteration Pregnant patients, who wish to conceive or who are in the nursing period.

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
Intervention Model: Single Group Assignment
Interventional Model Description: A prospective, open-label, single-arm, multicenter, 12-week study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAK-free latanoprost ophthalmic emulsion<br>Patients with primary open-angle glaucoma who were using BAK-containing latanoprost ophthalmic solution for ≥ 6 months (baseline), switched to a new formulation of latanoprost ophthalmic product | Drug: Latanoprost Ophthalmic Product<br>* Multidose bottle, preserved with potassium sorbate, that can be stored at room temperature up to 30°C during all shelf life, the emulsion does not require shaking before use<br>* Other names: Louten® Emulsion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular pressure | Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine it. IOP is an important aspect in the evaluation of patients at risk from glaucoma. Most tonometers measure pressure in millimeters of mercury (mmHg). | At the baseline (still on treatment with BAK-containing latanoprost) | 
| Intraocular pressure | Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine it. IOP is an important aspect in the evaluation of patients at risk from glaucoma. Most tonometers measure pressure in millimeters of mercury (mmHg). | After 4 weeks of treatment with BAK-free latanoprost | 
| Intraocular pressure | Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine it. IOP is an important aspect in the evaluation of patients at risk from glaucoma. Most tonometers measure pressure in millimeters of mercury (mmHg). | After 8 weeks of treatment with BAK-free latanoprost | 
| Intraocular pressure | Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine it. IOP is an important aspect in the evaluation of patients at risk from glaucoma. Most tonometers measure pressure in millimeters of mercury (mmHg). | After 12 weeks of treatment with BAK-free latanoprost | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Surface Disease Index (OSDI) | The OSDI score is a valid and reliable instrument for measuring dry eye disease severity (normal, mild to moderate, and sever) and effect on vision related function. It is determined using OSDI questionnaire (score). The OSDI score is assessed on a scale of 0 to 100, with higher scores representing greater disability. The index demonstrates sensitivity and specificity in distinguishing between normal patients and patients with dry eye disease. | At the baseline (still on treatment with BAK-containing latanoprost) | 
| Ocular Surface Disease Index (OSDI) | The OSDI score is a valid and reliable instrument for measuring dry eye disease severity (normal, mild to moderate, and sever) and effect on vision related function. It is determined using OSDI questionnaire (score). The OSDI score is assessed on a scale of 0 to 100, with higher scores representing greater disability. The index demonstrates sensitivity and specificity in distinguishing between normal patients and patients with dry eye disease. | After 4 weeks of treatment with BAK-free latanoprost | 
| Ocular Surface Disease Index (OSDI) | The OSDI score is a valid and reliable instrument for measuring dry eye disease severity (normal, mild to moderate, and sever) and effect on vision related function. It is determined using OSDI questionnaire (score). The OSDI score is assessed on a scale of 0 to 100, with higher scores representing greater disability. The index demonstrates sensitivity and specificity in distinguishing between normal patients and patients with dry eye disease. | After 8 weeks of treatment with BAK-free latanoprost | 
| Ocular Surface Disease Index (OSDI) | The OSDI score is a valid and reliable instrument for measuring dry eye disease severity (normal, mild to moderate, and sever) and effect on vision related function. It is determined using OSDI questionnaire (score). The OSDI score is assessed on a scale of 0 to 100, with higher scores representing greater disability. The index demonstrates sensitivity and specificity in distinguishing between normal patients and patients with dry eye disease. | After 12 weeks of treatment with BAK-free latanoprost | 
| Conjunctival hyperemia | Patients on treatment with prostaglandin analogues preserved with BAK suffer from conjunctival hyperemia. It is the most common side effect that leads to discontinuation or non-compliance. It is determined with the slit lamp. It is classified as patients without hyperemia or with mild, moderate, or severe hyperemia. | At the baseline (still on treatment with BAK-containing latanoprost) | 
| Conjunctival hyperemia | Patients on treatment with prostaglandin analogues preserved with BAK suffer from conjunctival hyperemia. It is the most common side effect that leads to discontinuation or non-compliance. It is determined with the slit lamp. It is classified as patients without hyperemia or with mild, moderate, or severe hyperemia. | After 4 weeks of treatment with BAK-free latanoprost | 
| Conjunctival hyperemia | Patients on treatment with prostaglandin analogues preserved with BAK suffer from conjunctival hyperemia. It is the most common side effect that leads to discontinuation or non-compliance. It is determined with the slit lamp. It is classified as patients without hyperemia or with mild, moderate, or severe hyperemia. | After 8 weeks of treatment with BAK-free latanoprost | 
| Conjunctival hyperemia | Patients on treatment with prostaglandin analogues preserved with BAK suffer from conjunctival hyperemia. It is the most common side effect that leads to discontinuation or non-compliance. It is determined with the slit lamp. It is classified as patients without hyperemia or with mild, moderate, or severe hyperemia. | After 12 weeks of treatment with BAK-free latanoprost | 
| Schirmer I test | Schirmer test measures the production of tears. This test consists of placing a small strip of filter paper inside the lower eyelid (inferior fornix). The eyes are closed for 5 minutes. The paper is then removed and the amount of moisture is measured (millimeter). | At the baseline (still on treatment with BAK-containing latanoprost) | 
| Schirmer I test | Schirmer test measures the production of tears. This test consists of placing a small strip of filter paper inside the lower eyelid (inferior fornix). The eyes are closed for 5 minutes. The paper is then removed and the amount of moisture is measured (millimeter). | After 4 weeks of treatment with BAK-free latanoprost | 
| Schirmer I test | Schirmer test measures the production of tears. This test consists of placing a small strip of filter paper inside the lower eyelid (inferior fornix). The eyes are closed for 5 minutes. The paper is then removed and the amount of moisture is measured (millimeter). | After 8 weeks of treatment with BAK-free latanoprost | 
| Schirmer I test | Schirmer test measures the production of tears. This test consists of placing a small strip of filter paper inside the lower eyelid (inferior fornix). The eyes are closed for 5 minutes. The paper is then removed and the amount of moisture is measured (millimeter). | After 12 weeks of treatment with BAK-free latanoprost | 
| Break up time (BUT) | Tear film break-up time (TBUT) is a method for determining the stability of the tear film and checking evaporative dry eye. In testing for TBUT, sodium fluorescein dye is added to the eye and the tear film is observed under the slit lamp while the patient avoids blinking until tiny dry spots develop. The BUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film. | At the baseline (still on treatment with BAK-containing latanoprost) | 
| Break up time (BUT) | Tear film break-up time (TBUT) is a method for determining the stability of the tear film and checking evaporative dry eye. In testing for TBUT, sodium fluorescein dye is added to the eye and the tear film is observed under the slit lamp while the patient avoids blinking until tiny dry spots develop. The BUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film. | After 4 weeks of treatment with BAK-free latanoprost | 
| Break up time (BUT) | Tear film break-up time (TBUT) is a method for determining the stability of the tear film and checking evaporative dry eye. In testing for TBUT, sodium fluorescein dye is added to the eye and the tear film is observed under the slit lamp while the patient avoids blinking until tiny dry spots develop. The BUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film. | After 8 weeks of treatment with BAK-free latanoprost | 
| Break up time (BUT) | Tear film break-up time (TBUT) is a method for determining the stability of the tear film and checking evaporative dry eye. In testing for TBUT, sodium fluorescein dye is added to the eye and the tear film is observed under the slit lamp while the patient avoids blinking until tiny dry spots develop. The BUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film. | After 12 weeks of treatment with BAK-free latanoprost | 
| Corneal epithelial fluorescein staining | This is a test that uses orange dye (fluorescein) and a blue light to detect damage to the cornea. Fluorescein does not stain intact corneal epithelium but does stain corneal stroma, thus demarcating the area of the epithelial loss. Number of patients with corneal epithelial defects classified as inferior punctata keratitis or central corneal keratitis. | At the baseline (still on treatment with BAK-containing latanoprost) | 
| Corneal epithelial fluorescein staining | This is a test that uses orange dye (fluorescein) and a blue light to detect damage to the cornea. Fluorescein does not stain intact corneal epithelium but does stain corneal stroma, thus demarcating the area of the epithelial loss. Number of patients with corneal epithelial defects classified as inferior punctata keratitis or central corneal keratitis. | After 4 weeks of treatment with BAK-free latanoprost | 
| Corneal epithelial fluorescein staining | This is a test that uses orange dye (fluorescein) and a blue light to detect damage to the cornea. Fluorescein does not stain intact corneal epithelium but does stain corneal stroma, thus demarcating the area of the epithelial loss. Number of patients with corneal epithelial defects classified as inferior punctata keratitis or central corneal keratitis. | After 8 weeks of treatment with BAK-free latanoprost | 
| Corneal epithelial fluorescein staining | This is a test that uses orange dye (fluorescein) and a blue light to detect damage to the cornea. Fluorescein does not stain intact corneal epithelium but does stain corneal stroma, thus demarcating the area of the epithelial loss. Number of patients with corneal epithelial defects classified as inferior punctata keratitis or central corneal keratitis. | After 12 weeks of treatment with BAK-free latanoprost | 
| Tear meniscus height | The height of the tear meniscus is related to the tear secretion rate and tear stability, and it is a good indicator of the overall tear volume. It is measured with a slit lamp and classified as normal, increased or decreased (millimeter). | At the baseline (still on treatment with BAK-containing latanoprost) | 
| Tear meniscus height | The height of the tear meniscus is related to the tear secretion rate and tear stability, and it is a good indicator of the overall tear volume. It is measured with a slit lamp and classified as normal, increased or decreased (millimeter). | After 4 weeks of treatment with BAK-free latanoprost | 
| Tear meniscus height | The height of the tear meniscus is related to the tear secretion rate and tear stability, and it is a good indicator of the overall tear volume. It is measured with a slit lamp and classified as normal, increased or decreased (millimeter). | After 8 weeks of treatment with BAK-free latanoprost | 
| Tear meniscus height | The height of the tear meniscus is related to the tear secretion rate and tear stability, and it is a good indicator of the overall tear volume. It is measured with a slit lamp and classified as normal, increased or decreased (millimeter). | After 12 weeks of treatment with BAK-free latanoprost | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OSDI, Benzalkonium Chloride, Latanoprost, BAK-free, Glaucoma, Ocular hypertension, conjunctival hyperemia, BUT, Schirmer I, Corneal staining, Tear meniscus height