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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Open-angle Glaucoma
• Intervention / Treatment: Drug: Latanoprost Ophthalmic Product

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1407
    • Laboratoarios Poen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAK-free latanoprost ophthalmic emulsion; 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; 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; Other Names: Louten® Emulsion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Laboratorios Poen
• Investigators: Principal Investigator: Alejo Peyret, PhD, Hospital Durand, Argentina; Study Chair: Javier Casiraghi, PhD, Hospital de Clinicas "Jose De San Martin"; Study Director: Daniel Grigera, PhD, Hospital Santa Lúcia

Publications and helpful links

General Publications

• Walimbe T, Chelerkar V, Bhagat P, Joshi A, Raut A. Effect of benzalkonium chloride-free latanoprost ophthalmic solution on ocular surface in patients with glaucoma. Clin Ophthalmol. 2016 May 9;10:821-7. doi: 10.2147/OPTH.S102976. eCollection 2016.
• Munoz Negrete FJ, Lemij HG, Erb C. Switching to preservative-free latanoprost: impact on tolerability and patient satisfaction. Clin Ophthalmol. 2017 Mar 21;11:557-566. doi: 10.2147/OPTH.S126042. eCollection 2017. Erratum In: Clin Ophthalmol. 2017 May 11;11:887.
• Cucherat M, Stalmans I, Rouland JF. Relative efficacy and safety of preservative-free latanoprost (T2345) for the treatment of open-angle glaucoma and ocular hypertension: an adjusted Indirect comparison meta-analysis of randomized clinical trials. J Glaucoma. 2014 Jan;23(1):e69-75. doi: 10.1097/IJG.0b013e3182a075e6.
• Denis P; Monoprost French Study Group. [Unpreserved latanoprost in the treatment of open-angle glaucoma and ocular hypertension. A multicenter, randomized, controlled study]. J Fr Ophtalmol. 2016 Sep;39(7):622-30. doi: 10.1016/j.jfo.2016.05.006. Epub 2016 Aug 25. French.
• Sanford M. Preservative-free latanoprost eye drops in patients with primary open-angle glaucoma/ocular hypertension. Clin Drug Investig. 2014 Jul;34(7):521-8. doi: 10.1007/s40261-014-0203-4.

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2017
• Primary Completion (Actual): October 6, 2017
• Study Completion (Actual): October 6, 2017

Study Registration Dates

• First Submitted: October 25, 2017
• First Submitted That Met QC Criteria: October 31, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 8, 2017
• Last Update Submitted That Met QC Criteria: November 6, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Ocular hypertension; Glaucoma; Latanoprost; OSDI; Corneal staining; Benzalkonium Chloride; BAK-free; conjunctival hyperemia; BUT; Schirmer I; Tear meniscus height
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Glaucoma, Open-Angle; Pharmaceutical Solutions; Ophthalmic Solutions; Latanoprost
• Other Study ID Numbers: SOLEMU03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No