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

• Sponsor: Allergan (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02965846
• Collaborator: (none)
• Enrollment: 43
• Locations: 49
• Arms: 2
• Actual Duration (Months): 6
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes	Drug: AGN-195263; Drug: Vehicle	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Topical Ophthalmic AGN-195263 for the Treatment of Evaporative Dry Eye
• Actual Study Start Date: Dec 13, 2016
• Actual Primary Completion Date: Jun 13, 2017
• Actual Study Completion Date: Jun 13, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Overall Ocular Discomfort Score (0 to 4 Scale; 0=None, 4=Very Severe) [6 month visit]

   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.

Secondary Outcome Measures

1. Change From Baseline in Tearfilm Break Up Time (TBUT) [Baseline (day 1) to 6 month visit]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Khristopher Hansen, Allergan

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 26, 2016

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02965846
• Other Study ID Numbers: 195263-010
• First Posted: Nov 17, 2016
• Last Update Posted: Nov 30, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by Allergan: EDE; evaporative dry eye
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca

Study Results

Participant Flow

Pre-assignment Detail	Of the 43 participants who enrolled in the study, 10 were randomized and received intervention to compromise the safety and Intent to Treat (ITT) populations

Arm/Group Title	AGN-195263	Vehicle	Enrolled But Not Randomized
Arm/Group Description	One drop of 0.1% AGN-195263 instilled in each eye twice daily	One drop of Vehicle (placebo) instilled in each eye twice daily	Run-In period before randomization
Period Title: Overall Study
STARTED	5	5	33
COMPLETED	0	0	0
NOT COMPLETED	5	5	33

Baseline Characteristics

Arm/Group Title	AGN-195263	Vehicle	Enrolled But Not Randomized	Total
Arm/Group Description	One drop of 0.1% AGN-195263 instilled in each eye twice daily	One drop of Vehicle (placebo) instilled in each eye twice daily	Run-In period before randomization	Total of all reporting groups
Overall Participants	5	5	33	43
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	4 80%	27 81.8%	36 83.7%
>=65 years	0 0%	1 20%	6 18.2%	7 16.3%
Sex: Female, Male (Count of Participants)
Female	2 40%	1 20%	23 69.7%	26 60.5%
Male	3 60%	4 80%	10 30.3%	17 39.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	6 18.2%	6 14%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 3%	1 2.3%
Black or African American	3 60%	4 80%	10 30.3%	17 39.5%
White	2 40%	1 20%	16 48.5%	19 44.2%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	34.34 (10.649807509998)	34.86 (9.1331484166195)	32.788 (9.4405643899081)	33.996 (.65464394984732)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	101.44 (23.543542639119)	102.56 (20.180247768548)	87.868 (25.016006395906)	97.2893 (2.0238704230461)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	173.44 (5.6683683719391)	172.9 (5.8343808583259)	163.74 (9.2099077085495)	170.026 (1.6317762147419)

Outcome Measures

1. Primary Outcome

Title	Overall Ocular Discomfort Score (0 to 4 Scale; 0=None, 4=Very Severe)
Description	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.
Time Frame	6 month visit

Outcome Measure Data

Analysis Population Description

Efficacy analyses including the overall ocular discomfort score were planned. Ultimately, these analyses were not performed due to the fact that the study was terminated before the primary/secondary efficacy visit could be reached.

Arm/Group Title	AGN-195263	Vehicle
Arm/Group Description	One drop of 0.1% AGN-195263 instilled in each eye twice daily	One drop of Vehicle (placebo) instilled in each eye twice daily
Measure Participants	0	0

2. Secondary Outcome

Title	Change From Baseline in Tearfilm Break Up Time (TBUT)
Description	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.
Time Frame	Baseline (day 1) to 6 month visit

Outcome Measure Data

Analysis Population Description

Efficacy analyses including the change from baseline in Tearfilm Break Up Time (TBUT) were planned. Ultimately, these analyses were not performed due to the fact that the study was terminated before the primary/secondary efficacy visit could be reached.

Arm/Group Title	AGN-195263	Vehicle
Arm/Group Description	One drop of 0.1% AGN-195263 instilled in each eye twice daily	One drop of Vehicle (placebo) instilled in each eye twice daily
Measure Participants	0	0

Adverse Events

Time Frame	Up to 157 days
Adverse Event Reporting Description	Adverse Events were collected for randomized patients only.
Arm/Group Title	AGN-195263		Vehicle
Arm/Group Description	One drop of 0.1% AGN-195263 instilled in each eye twice daily		One drop of Vehicle (placebo) instilled in each eye twice daily
All Cause Mortality
	AGN-195263		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Serious Adverse Events
	AGN-195263		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	AGN-195263		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		1/5 (20%)
Eye disorders
Vision Blurred	0/5 (0%)	0	1/5 (20%)	1

Limitations/Caveats

Due to study termination, the study was underpowered

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

As this study was terminated, no data will be published.