Topical Ophthalmic AGN-195263 for the Treatment of Evaporative Dry Eye

The objectives of this study are twofold •To evaluate the safety and efficacy of 0.1% AGN-195263 administered twice daily compared to its vehicle in patients with evaporative dry eye (EDE) •To evaluate the systemic pharmacokinetics of 0.1% AGN-195263 administered twice daily in patients with EDE

Study Overview

• Status: Terminated
• Conditions: Dry Eye Syndromes
• Intervention / Treatment: Drug: AGN-195263; Drug: Vehicle

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Ostrava, Czechia, 708 52
    • Fakultni Nemocnice Ostrava
  • Pardubice, Czechia, 530 02
    • Ocni klinika Oftex
  • Praha 10, Czechia, 100 34
    • FN Kralovske Vinohrady, Ocni Klinika
  • Velká Bíteš, Czechia, 595 01
    • Ocni ambulance
• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux, Service d'Ophtalmologie
  • Brest Cedex, France, 29609
    • CHU Hopital Morvan (Bat 4) Service Daviel Ophtalmologie
  • Limoges Cedex, France, 87042
    • CHU Limoges - Hôpital Dupuytren
• Germany
  • Dusseldorf, Germany, 40225
    • Augenklinik Universitatsklinikum
  • Freiburg, Germany, 79106
    • University Eye Hospital
  • Koln, Germany, 50937
    • University Hospital of Cologne, Dept of Ophthalmology
  • Mainz, Germany, 55131
    • Gutenberg University Medical School, Dept of Ophthalmology
  • Munich, Germany, 80366
    • Ludwig-Maximilians-University, Dept of Ophthalmology
  • Munster, Germany, 48145
    • St. Franziskus Hospital Augenabteilung
• Hungary
  • Budapest, Hungary, H-1085
    • Dept. of Ophthalmology Semmelweis University
  • Debrecen, Hungary, H-4032
    • University of Debrecen, Dept of Opthalmology, (DE OEC Szemklinika)
  • Szeged, Hungary, H-6720
    • University of Szeged Szent-Györgyi Albert Clinical Center, Faculty of Medicine, Dept of Ophthalmology
• Italy
  • Genova, Italy, 16035
    • Rapallo Hospital, Opthalmology Department
  • Messina, Italy, 98122
    • Istituto di Oftalmologia
  • Milano, Italy, 20123
    • Ospedale San Giuseppe, Universita di Milano
  • Milano, Italy, 20132
    • Istituto Di Ricovero E Cura A Carattere Scientifico (IRCCS) - Ospedale San Raffaele (HSR) (Istituto Scientifico Universitario San Raffaele)
  • Pisa, Italy, 56126
    • University of Pisa, Neurosciences - Section of Ophthalmology
• Philippines
  • Makati City, Philippines, 1200
    • Asian Eye Institute
  • Makati City, Philippines, 1209
    • Peregrine Eye and Laser Institute
  • Pasig City, Philippines, 1605
    • The Medical City
• Poland
  • Bydgoszcz, Poland, 85-631
    • Prywatna Klinika Okulistyczna OFTALMIKA
  • Bytom, Poland, 41-902
    • Szpital Specjalistyczny Nr 1 w Bytomiu
  • Gdansk, Poland, 80-809
    • Optimum Profesorskie Centrum Okulistyki
  • Katowice, Poland, 43-300
    • Specjalistyczna Praktyka Lekarska prof. Edward Wylegala
  • Wroclaw, Poland, 50-556
    • Uniwersyteck Szpital Kliniczny im. Jana Mikulicza-Radeckiego
• Spain
  • Barcelona, Spain, 08035
    • Institto de Microcirugia Ocular C/Josep Maria Llado
  • Barcelona, Spain, 8028
    • Clinico de Barcelona Casa de la Maternidad
  • Huelva, Spain, 21004
    • Clínica Oftalmológica
  • Oviedo, Principado De Asturias, Spain, 33012
    • Instituto Oftalmologico Fernandez-Vega
  • Sevilla, Spain, 41003
    • Cartuja Vision
  • Valladolid, Spain, 47005
    • University of Valladolid, Facultad Medicina
• Taiwan
  • Hualien, Taiwan, 970
    • Buddhist Tzu Chi General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11447
    • Tri-Service General Hospital
• Turkey
  • Izmir, Turkey, 35040
    • Ege Üniv. Tıp Fakültesi
  • Kayseri, Turkey, 38039
    • Erciyes Üniversitesi Tıp Fakültesi
• United Kingdom
  • Newcastle-upon-Tyne, United Kingdom, NE1 4LP
    • Newcastle University School of Medicine, Dept of Ophthamology
• United States
  • California
    • Artesia, California, United States, 90701
      • Sall Research Medical Center
    • Glendale, California, United States, 91204
      • Lugene Eye Institute
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Lifelong Vision Foundation
  • Oregon
    • Portland, Oregon, United States, 97210
      • Devers Eye Institute
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • Scott and Christie Associates
    • Philadelphia, Pennsylvania, United States, 19107
      • Wills Eye Hospital
  • Texas
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center

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:

• Male, 18 years of age or older, at the screening (day -51) visit OR
• Females, who are naturally postmenopausal (permanent cessation of menstrual periods for at least 12 consecutive months) or are permanently sterilized (ie, eg, tubal occlusion,hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy) at the screening (day -51) visit

• In at least 1 eye, all of the following objective measures of evaporative dry eye (EDE) must be present at the standardization (day -21) and baseline (day 1) visits. The same eye must qualify at both visits

  • Tear film break-up time (TBUT) ≥ 2 seconds and ≤ 7 seconds
  • Corneal sodium fluorescein staining score ≥ 1 and ≤ 4 (Oxford scheme)
  • Anesthetized Schirmer's tear test score ≥ 10 mm after 5 minutes

• At the standardization (day -21) and baseline (day 1) visits, patients must have:

  • Ocular Surface Disease Index© (OSDI) score > 12 (0 to 100 scale)
  • Overall ocular discomfort score ≥ 1 and < 4 (0 to 4 scale; 0 = none, 4 = very severe)
  • Ocular burning score ≥ 1 and < 4 (0 to 4 scale; 0 = none, 4 = very severe)
  • Blurred vision score ≥ 1 and < 4 (0 to 4 scale; 0 = none, 4 = very severe)
• In at least 1 eye, a lower lid margin meibum quality global assessment score ≥ 1 at the standardization (day -21) and baseline (day 1) visits. The same eye must qualify at both visits
• In at least 1 eye, the number of lower lid margin expressible meibomian glands must be ≥ 3 at the standardization (day -21) and baseline (day 1) visits. The same eye must qualify at both visits
• Use of an artificial tear product, lid hygiene (ie, warm compress, lid massage, lid scrub), omega-3 supplementation (topical ocular or systemic), or antibiotics (ie, systemic or topical macrolides, tetracyclines, tetracycline derivatives [including doxycycline and minocycline]) for the treatment of dry eye disease, or meibomian gland disease within 1 year of the standardization (day -21) visit

Exclusion Criteria:

• Male patients with a history of, known, or suspected prostate cancer
• Male patients with a prostate-specific antigen (PSA) level ≥ 4 μg/L
• Female patients with a history of known or suspected breast, cervical, ovarian, or uterine cancer
• Female patient who is of child-bearing potential
• At standardization (day -21) and / or baseline (day 1) visits, a lower lid margin meibum quality global assessment score of non-expressible (NE) in either eye
• Patients who are currently using estrogen and/or progesterone containing products (including herbal and nutritional supplements) and not on a stable dose (at least 90 days prior to the standardization visit (day -21) and/or anticipate initiating use and/or changing use during the study
• Patients who are currently using or have used any androgen or anti-androgen treatment (including herbal and nutritional supplements), within 90 days of the standardization (day -21) visit or anticipated use during the study
• Patients who are currently using or have used any hair growth product within 90 days of the standardization (day -21) visit or anticipated use during the study
• Patients who are currently using or have used topical corticosteroids in the eyes or on the eyelids within 60 days prior to the standardization visit (day -21), or any such use anticipated prior to the month 6 visit
• Patients who are currently using or have used oral or topical macrolides, tetracyclines, tetracycline derivative drugs (including doxycycline and minocycline), retinoids (eg, isotretinoin), calcineurin inhibitors (ie, RESTASIS®, Ikervis®), oral (systemic) corticosteroids, or lifitegrast (Xiidra™) or any other therapeutic dry eye treatment within 60 days of the standardization visit (day -21), or anticipated use before the month 6 visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vehicle	Drug: Vehicle; 1 drop of AGN-195263 vehicle(placebo) will be instilled in each eye twice daily.
Experimental: AGN-195263	Drug: AGN-195263; 1 drop of AGN-195263 will be instilled in each eye twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Ocular Discomfort Score (0 to 4 Scale; 0=None, 4=Very Severe)	The overall ocular discomfort will be assessed on a questionnaire using a 0 to 4 scale on which 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe.	6 month visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Tearfilm Break Up Time (TBUT)	For TBUT, the mean of 3 measurements of time in seconds will be computed at each visit for each eye. The mean value of the study eye will be used for the analysis.	Baseline (day 1) to 6 month visit

Collaborators and Investigators

• Sponsor: Allergan
• Investigators: Study Director: Khristopher Hansen, Allergan

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2016
• Primary Completion (Actual): June 13, 2017
• Study Completion (Actual): June 13, 2017

Study Registration Dates

• First Submitted: November 15, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): November 30, 2018
• Last Update Submitted That Met QC Criteria: November 29, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: EDE; evaporative dry eye
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca
• Other Study ID Numbers: 195263-010