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

• Sponsor: Allergan (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02815293
• Collaborator: (none)
• Enrollment: 36
• Locations: 29
• Arms: 2
• Actual Duration (Months): 8.7
• Patients Per Site: 1.2
• 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: 36 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: Sep 30, 2016
• Actual Primary Completion Date: Jun 21, 2017
• Actual Study Completion Date: Jun 21, 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 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 or lid hygiene (ie, warm compress, lid massage, lid scrub) for the treatment of dry eye disease, EDE 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 or have used hormone replacement therapy or estrogen and /or progesterone based products (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 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 corticosteroids administered via any route within 30 days prior to the standardization (day -21) visit, or any anticipated use via any route of administration prior to the month 6 visit

• Patients who are currently using or have used oral or topical macrolides, tetracycline, tetracycline derivative drugs (including doxycycline and minocycline), retinoids (eg, isotretinoin), or calcineurin inhibitors (ie, RESTASIS®, Ikervis®) within 60 days of the standardization (day -21) visit, or anticipated use prior to the month 6 visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Eye Center	Chandler	Arizona	United States	85225
2	Clearsight	Fullerton	California	United States	92835
3	Orange County Ophthalmology Medical Group	Garden Grove	California	United States	92843
4	Montebello Medical Center, Inc.	Montebello	California	United States	90640
5	Eye Research Foundation	Newport Beach	California	United States	92663
6	North Bay Eye Associates	Petaluma	California	United States	94954
7	Martel Eye Medical Group	Rancho Cordova	California	United States	95670
8	Centennial Eye and Cosmetic Associates	Centennial	Colorado	United States	80016
9	Specialty Eye Care	Parker	Colorado	United States	80134
10	Argus Research at Cape Coral Eye Center	Cape Coral	Florida	United States	33904
11	Sarasota Retina Institute	Sarasota	Florida	United States	34239
12	Eye Care Centers Management, Inc. dba Clayton Eye Center	Morrow	Georgia	United States	30260
13	Taustine Eye Center	Louisville	Kentucky	United States	40217
14	Eye Doctors of Washington	Chevy Chase	Maryland	United States	20815
15	Ophthalmology Consultants, Ltd	Saint Louis	Missouri	United States	63131
16	Mercy Medical Research Institute	Springfield	Missouri	United States	65804
17	Comprehensive Eye Care	Washington	Missouri	United States	63090
18	Cornerstone Eye Care, LLC	High Point	North Carolina	United States	27262
19	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
20	Carolina Macula and Retina	Mount Pleasant	South Carolina	United States	29464
21	Nashville Vision Associates, LLC	Nashville	Tennessee	United States	37205
22	Robert Cizik Eye Clinic	Houston	Texas	United States	77030
23	Houston Eye Associates	Kingwood	Texas	United States	77339
24	Brazosport Eye Institute	Lake Jackson	Texas	United States	77566
25	The Eye Clinic of Texas, an affiliate of Houston Eye Associates	League City	Texas	United States	77573
26	DCT- Shah Research, LLC dba Discovery Clinical Trials	Mission	Texas	United States	78572
27	R and R Eye Research, LLC	San Antonio	Texas	United States	78229
28	Stacy R. Smith, M.D., P.C.	Salt Lake City	Utah	United States	84117
29	The Eye Centers of Racine and Kenosha	Racine	Wisconsin	United States	53405

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, 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: NCT02815293
• Other Study ID Numbers: 195263-009
• First Posted: Jun 28, 2016
• Last Update Posted: Feb 19, 2019
• Last Verified: Feb 1, 2019

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

Study Results

Participant Flow

Recruitment Details	Of the 36 participants who enrolled in the study, 18 were randomized and received intervention to comprise the safety and Intent to Treat (ITT) populations
Pre-assignment Detail	This study was terminated

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 AGN-195263 vehicle (placebo) instilled in each eye twice daily.	Run-In period before randomization
Period Title: Overall Study
STARTED	10	8	18
COMPLETED	0	0	0
NOT COMPLETED	10	8	18

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 AGN-195263 vehicle (placebo) instilled in each eye twice daily.	Run-In period before randomization	Total of all reporting groups
Overall Participants	10	8	18	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 60%	3 37.5%	9 50%	18 50%
>=65 years	4 40%	5 62.5%	9 50%	18 50%
Sex: Female, Male (Count of Participants)
Female	7 70%	3 37.5%	12 66.7%	22 61.1%
Male	3 30%	5 62.5%	6 33.3%	14 38.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 12.5%	2 11.1%	3 8.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 20%	1 12.5%	6 33.3%	9 25%
White	8 80%	6 75%	10 55.6%	24 66.7%
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 (weight (kg) / height (m)^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weight (kg) / height (m)^2]	27.43 (4.4580376849013)	27.3375 (4.8256961932969)	29.6 (7.4233864689013)	28.1225 (1.3197836926109)
Weight (Kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg]	73.32 (11.022504252664)	74.3 (16.250384610833)	82.68 (19.69071093745)	76.76 (3.5637743007958)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	163.78 (8.5922988774833)	165.0875 (17.14697039567)	167.63 (9.8016438530597)	165.499 (3.7800461794887)

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 for the intent-to-treat (ITT) population who are defined as all randomized patients. Ultimately, these analyses were not fully performed due to the early termination of the study and only six patients reaching the 6 month visit.

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 AGN-195263 vehicle (placebo) instilled in each eye twice daily.
Measure Participants	3	3
Mean (Standard Deviation) [Score on a scale]	1.66 (0.513)	1.75 (0.204)

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 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 fully performed due to the early termination of the study and only six patients reaching the 6 month visit.

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 AGN-195263 vehicle (placebo) instilled in each eye twice daily.
Measure Participants	3	3
Mean (Standard Deviation) [Seconds]	3.18 (0.284)	3.16 (0.286)

Adverse Events

Time Frame	Up to 223 days
Adverse Event Reporting Description	Adverse Events reported 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 AGN-195263 vehicle (placebo) instilled in each eye twice daily.
All Cause Mortality
	AGN-195263		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)
Serious Adverse Events
	AGN-195263		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/8 (12.5%)
Injury, poisoning and procedural complications
Laceration	0/10 (0%)		1/8 (12.5%)
Other (Not Including Serious) Adverse Events
	AGN-195263		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		2/8 (25%)
Eye disorders
Conjunctival haemorrhage	0/10 (0%)		1/8 (12.5%)
Eye irritation	0/10 (0%)		1/8 (12.5%)

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.