Evaluation of the Corneal Residence Time of Chitosan-N-acetylcysteine Eye Drops in Patients With Dry Eye Syndrome After Single and Multiple Instillation

Sponsor

Gerhard Garhofer (Other)

Overall Status

Completed

CT.gov ID

NCT01753752

Collaborator

Croma-Pharma GmbH (Industry)

Enrollment

Location

Arms

5.9

Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In the elderly population, dry eye syndrome is a highly prevalent ocular disease. One mainstay of therapy for patients suffering from dry eye syndrome is the use of topically administered lubricants. One of the main disadvantages of the formulations currently available for the treatment of DES is the short residency time on the ocular surface, which increases the need for a frequent instillation of the lubricant.

Recently, Croma Pharma has introduced chitosan-N-acetylcysteine eye drops, designed for treatment of symptoms related to DES. Based on theoretical considerations and animal experiments, the new chitosan derivative may show an increased adhesion to mucins of the ocular surface and may therefore considerably increase the residence on the ocular surface. This, in turn, would limit the need for frequent treatment and decrease the burden for the patients.

It has been shown in recent Phase I studies that chitosan-N-acetylcysteine eye drops are safe and well tolerated after single and repeated instillation. The current study seeks to investigate the ocular residency time after a single dose and after 5 day b.i.d. treatment. For this purpose 2 cohorts are planned: In Cohort I, chitosan-N-acetylcysteine eye drops will be instilled once in one randomly chosen eye, whereas the fellow eye will receive placebo. Measurements of tear film thickness will be performed with optical coherence tomography (OCT) before instillation and 10 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 10 hours, 12 hours and 24 hours after instillation. In addition, ocular scattering of the tear film will be assessed with an Optical Quality Analysis System (OQAS) at the same timepoints. Determination of break up time (BUT) will be performed before and after instillation of the eye drops.

In Cohort II, chitosan-N-acetylcysteine eye drops will be instilled once daily in one eye and b.i.d. in the fellow eye on five consecutive days. Measurements of tear film thickness with OCT and OQAS will be performed every study day before the morning instillation and the day after the last instillation. Additionally, patients will be asked to answer the ocular surface disease index (OSDI©) on day 1 and day 6. BUT will be determined before and after instillation of the eye drops.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndrome	Drug: Chitosan- N- Acetylcysteine eye drops Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Study Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chitosan-N-acetylcystein Instillation into the study eye	Drug: Chitosan- N- Acetylcysteine eye drops
Placebo Comparator: Placebo Instillation into the fellow eye	Drug: Placebo

Arm

Intervention/Treatment

Experimental: Chitosan-N-acetylcystein

Instillation into the study eye

Drug: Chitosan- N- Acetylcysteine eye drops

Placebo Comparator: Placebo

Instillation into the fellow eye

Drug: Placebo

Outcome Measures

Primary Outcome Measures

Tear Film thickness as measured with OCT - Cohort I [Before, 10 minutes (± 3 minutes), 1 hour (± 10 minutes), 2 hours (± 10minutes), 4 hours (± 10 minutes), 8 hours (± 20 minutes) 10 hours (± 20 minutes) and 12 hours (± 20 minutes) after instillation]
Tear Film thickness as measured with OCT - Cohort II [change from baseline to after 6 days]
Tear film thickness will be assessed on 6 consecutive study days

Secondary Outcome Measures

OSI (Objective Scattering Index) - Cohort I [Before, 10 minutes (± 3 minutes), 1 hour (± 10 minutes), 2 hours (± 10minutes), 4 hours (± 10 minutes), 8 hours (± 20 minutes) 10 hours (± 20 minutes) and 12 hours (± 20 minutes) after instillation]
OSI (Objective Scattering Index) - Cohort II [change from baseline to after 6 days]
OSI will be assessed on 6 consecutive study days

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women aged over 18 years
History of dry eye syndrome for at least 3 months
At least two of the following three criteria must apply: - Tear Break Up Time (BUT) < 10 seconds and/or - Schirmer I test < 7 mm and/or - at least 2 symptoms of dry eye syndrome (foreign body sensation, burning, photophobia, blurred vision, pain, itching)
Normal ophthalmic findings except dry eye syndrome, ametropia < 6 Dpt.
No administration of topical lubricants 24 hours before the screening examination

Exclusion Criteria:

Participation in a clinical trial in the 3 weeks preceding the screening visit
Symptoms of a clinically relevant illness other than dry eye in the 3 weeks before the first study day
Presence or history of a severe medical condition as judged by the clinical investigator
Intake of parasympathomimetic or anti-psychotic drugs
Diagnosis of severe dry eye by Schirmer I test < 2mm
Difference in BUT between the two eyes of more than 4 seconds
Wearing of contact lenses
Glaucoma
Treatment with corticosteroids in the 4 weeks preceding the study
Topical treatment with any ophthalmic drug except topical lubricants in the 4 weeks preceding the study
Ocular infection or clinically significant inflammation
Ocular surgery in the 3 months preceding the study
Sjögren's syndrome
Stevens-Johnson syndrome
History of allergic conjunctivitis
Ametropia ≥ 6 Dpt
Pregnancy, planned pregnancy or lactating