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

This study has been completed.
Sponsor:
Collaborator:
Croma-Pharma GmbH
Information provided by (Responsible Party):
Gerhard Garhofer, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01753752
First received: December 7, 2012
Last updated: April 4, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Dry Eye Syndrome
Drug: Chitosan- N- Acetylcysteine eye drops
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Tear Film thickness as measured with OCT - Cohort I [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Tear Film thickness as measured with OCT - Cohort II [ Time Frame: change from baseline to after 6 days ] [ Designated as safety issue: No ]
    Tear film thickness will be assessed on 6 consecutive study days


Secondary Outcome Measures:
  • OSI (Objective Scattering Index) - Cohort I [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • OSI (Objective Scattering Index) - Cohort II [ Time Frame: change from baseline to after 6 days ] [ Designated as safety issue: No ]
    OSI will be assessed on 6 consecutive study days


Enrollment: 32
Study Start Date: September 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01753752

Locations
Austria
Medical University of Vienna, Department of Clinical Pharmacology
Vienna, Austria, 1090
Sponsors and Collaborators
Gerhard Garhofer
Croma-Pharma GmbH
  More Information

No publications provided

Responsible Party: Gerhard Garhofer, Assoc. Prof. Priv.-Doz. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01753752     History of Changes
Other Study ID Numbers: OPHT291211
Study First Received: December 7, 2012
Last Updated: April 4, 2013
Health Authority: Austria: Agency for Health and Food Safety

Additional relevant MeSH terms:
Dry Eye Syndromes
Keratoconjunctivitis Sicca
Lacrimal Apparatus Diseases
Eye Diseases
Keratoconjunctivitis
Conjunctivitis
Conjunctival Diseases
Keratitis
Corneal Diseases
Acetylcysteine
N-monoacetylcystine
Tetrahydrozoline
Ophthalmic Solutions
Chitosan
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes
Pharmaceutical Solutions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 14, 2014