A Study of AGN-195263 for the Treatment of Meibomian Gland Dysfunction

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01633788
• Collaborator: (none)
• Enrollment: 232
• Locations: 33
• Arms: 4
• Actual Duration (Months): 29.5
• Patients Per Site: 7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of AGN-195263 compared to vehicle in patients with meibomian gland dysfunction (MGD) in the eyelids.

Condition or Disease	Intervention/Treatment	Phase
Meibomian Gland Dysfunction	Drug: AGN-195263 0.1%; Drug: AGN-195263 0.03%; Drug: AGN-195263 0.01%; Drug: AGN-195263 Vehicle	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 232 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Actual Study Start Date: Aug 22, 2012
• Actual Primary Completion Date: Feb 5, 2015
• Actual Study Completion Date: Feb 5, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AGN-195263 0.1% 1 drop of AGN-195263 0.1% instilled in each eye twice daily.	Drug: AGN-195263 0.1%; 1 drop of AGN-195263 0.1% instilled in each eye twice daily.
Experimental: AGN-195263 0.03% 1 drop of AGN-195263 0.03% instilled in each eye twice daily.	Drug: AGN-195263 0.03%; 1 drop of AGN-195263 0.03% instilled in each eye twice daily.
Experimental: AGN-195263 0.01% 1 drop of AGN-195263 0.01% instilled in each eye twice daily.	Drug: AGN-195263 0.01%; 1 drop of AGN-195263 0.01% instilled in each eye twice daily.
Placebo Comparator: AGN-195263 Vehicle 1 drop of AGN-195263 vehicle (placebo) instilled in each eye twice daily.	Drug: AGN-195263 Vehicle; 1 drop of AGN-195263 vehicle (placebo) instilled in each eye twice daily.

Outcome Measures

Primary Outcome Measures

1. Percentage of Meibum Quality Responders in the Study Eye [Month 6]

   Meibum quality response is defined as a patient who experiences a reduction ≥ 50% in the number of meibomian glands with a Meibum Quality Score (MQS) of 2 or 3 in the study eye. The MQS is based on Mathers' meibum quality secretion grading 4-point scale where: 0 = Clear excreta or clear with small particles (normal viscosity), 1 = Opaque excreta with normal viscosity, 2 = Opaque excreta with increased viscosity (gel-like), and 3 = Secretions retain shape (or secretions do not express but a toothpaste-like substance can be seen at the opening of the orifice).

Secondary Outcome Measures

1. Percentage of Maximum Meibum Quality Score (MMQS) Responders in the Study Eye [Month 6]

   The MQS is assessed based on Mathers' meibum quality secretion grading 4-point scale where: 0 = Clear excreta or clear with small particles (normal viscosity), 1 = Opaque excreta with normal viscosity, 2 = Opaque excreta with increased viscosity (gel-like), and 3 = Secretions retain shape (or secretions do not express but a toothpaste-like substance can be seen at the opening of the orifice). MMQS is calculated for each eye as the maximum of the meibum quality scores of the expressible glands within the 6 central glands of the lower eyelids. A patient is considered to be an MMQS responder at a postrandomization visit if the MMQS in the study eye is 0 or 1 (indicating normal viscosity) at that visit.

2. Percentage of Complete Overall Ocular Discomfort Responders [Month 6]

   Ocular symptoms of blurred vision, burning, dryness, eye pain, light sensitivity, itching, and foreign body sensation are assessed by the patient on a 5-point scale ranging from 0 = none to 4 = very severe. A patient is considered a complete overall ocular discomfort responder if the overall ocular discomfort score is 0 (indicating no overall ocular discomfort) at that visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meibomian gland dysfunction in both eyes

• Best-corrected visual acuity of 20/40 or better in each eye

Exclusion Criteria:

• Known or suspected prostate cancer

• History of breast cancer

• Using LATISSE® or any other eye lash growth-stimulating product at least 30 days prior to the screening visit, or anticipated use during the study

• Contact lens wear in either eye during any portion of the study

• Unable to instill eye drops correctly

• History of corneal refractive surgery in either eye within 1 year

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cornea Consultants of Arizona	Phoenix	Arizona	United States	85032
2	University of Arkansas for Medical	Little Rock	Arkansas	United States	72205
3	Sall Research Medical Center	Artesia	California	United States	90701
4	Orange County Ophthalmology Medical Group, Inc.	Garden Grove	California	United States	92843
5	Lugene Eye Institute	Glendale	California	United States	91205
6	Lakeside Vision Center	Irvine	California	United States	92604
7	Scripps Clinic	La Jolla	California	United States	92037
8	North Valley Eye Medical Group, Inc.	Mission Hills	California	United States	91345
9	Eye Research Foundation	Newport Beach	California	United States	92663
10	North Bay Eye Associates, Inc.	Petaluma	California	United States	94954
11	Centennial Eye Associates	Centennial	Colorado	United States	80112
12	Colorado Eye Associates, PC	Colorado Springs	Colorado	United States	80907
13	Danbury Eye Physicians & Surgeons, PC	Danbury	Connecticut	United States	06810
14	The Eye Associates of Manatee, LLP	Bradenton	Florida	United States	34209
15	Wohl Eye Center	Bloomingdale	Illinois	United States	60108
16	John-Kenyon American Eye Institute	New Albany	Indiana	United States	47150
17	Durrie Vision	Overland Park	Kansas	United States	66061
18	Taustine Eye Center	Louisville	Kentucky	United States	40217
19	Lifelong Vision Foundation	Chesterfield	Missouri	United States	63017
20	Tauber Eye Center	Kansas City	Missouri	United States	64111
21	Ophthalmology Associates	Saint Louis	Missouri	United States	63131
22	Comprehensive Eye Care, Ltd.	Washington	Missouri	United States	63090
23	Northern New Jersey Eye Institute, PA	South Orange	New Jersey	United States	07079
24	Rochester Ophthalmological Group, PC	Rochester	New York	United States	14618
25	Ophthalmic Consultants Long Island	Rockville Centre	New York	United States	11570
26	South Shore Eye Care, LLP	Wantagh	New York	United States	11793
27	Cornerstone Eye Care	High Point	North Carolina	United States	27262
28	Drs. Fine, Hoffman, and Packer, LLC	Eugene	Oregon	United States	97401
29	Vision Center of Texas, PA	Cedar Park	Texas	United States	78613
30	University of Houston, College of Optometry	Houston	Texas	United States	77204
31	Focus Clinical Research	Salt Lake City	Utah	United States	84107
32	Stacy Smith, MD, PC	Salt Lake City	Utah	United States	84117
33	Virginia Eye Consultants	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01633788
• Other Study ID Numbers: 195263-006
• First Posted: Jul 4, 2012
• Last Update Posted: Sep 8, 2017
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Meibomian Gland Dysfunction

Study Results

Participant Flow

Pre-assignment Detail	Patients from one site were excluded from the modified intent-to-treat analysis population due to compliance issues. Patients from this site who received study treatment were included in the safety population and are reflected in the participant flow.

Arm/Group Title	AGN-195263 0.1%	AGN-195263 0.03%	AGN-195263 0.01%	AGN-195263 Vehicle
Arm/Group Description	1 drop of AGN-195263 0.1% instilled in each eye twice daily.	1 drop of AGN-195263 0.03% instilled in each eye twice daily.	1 drop of AGN-195263 0.01% instilled in each eye twice daily.	1 drop of AGN-195263 vehicle (placebo) instilled in each eye twice daily.
Period Title: Overall Study
STARTED	57	58	59	58
COMPLETED	50	50	49	45
NOT COMPLETED	7	8	10	13

Baseline Characteristics

Arm/Group Title	AGN-195263 0.1%	AGN-195263 0.03%	AGN-195263 0.01%	AGN-195263 Vehicle	Total
Arm/Group Description	1 drop of AGN-195263 0.1% instilled in each eye twice daily.	1 drop of AGN-195263 0.03% instilled in each eye twice daily.	1 drop of AGN-195263 0.01% instilled in each eye twice daily.	1 drop of AGN-195263 vehicle (placebo) instilled in each eye twice daily.	Total of all reporting groups
Overall Participants	57	58	59	58	232
Age, Customized (participants) [Number]
40 year to less than 55 years	17 29.8%	17 29.3%	20 33.9%	19 32.8%	73 31.5%
55 years to 65 years	26 45.6%	24 41.4%	19 32.2%	18 31%	87 37.5%
over 65 years	14 24.6%	17 29.3%	20 33.9%	21 36.2%	72 31%
Sex: Female, Male (Count of Participants)
Female	39 68.4%	39 67.2%	39 66.1%	39 67.2%	156 67.2%
Male	18 31.6%	19 32.8%	20 33.9%	19 32.8%	76 32.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Meibum Quality Responders in the Study Eye
Description	Meibum quality response is defined as a patient who experiences a reduction ≥ 50% in the number of meibomian glands with a Meibum Quality Score (MQS) of 2 or 3 in the study eye. The MQS is based on Mathers' meibum quality secretion grading 4-point scale where: 0 = Clear excreta or clear with small particles (normal viscosity), 1 = Opaque excreta with normal viscosity, 2 = Opaque excreta with increased viscosity (gel-like), and 3 = Secretions retain shape (or secretions do not express but a toothpaste-like substance can be seen at the opening of the orifice).
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat: all randomized and treated patients who have values for meibum quality score at randomization, at least one postrandomization visit, and data at the noted time point

Arm/Group Title	AGN-195263 0.1%	AGN-195263 0.03%	AGN-195263 0.01%	AGN-195263 Vehicle
Arm/Group Description	1 drop of AGN-195263 0.1% instilled in each eye twice daily.	1 drop of AGN-195263 0.03% instilled in each eye twice daily.	1 drop of AGN-195263 0.01% instilled in each eye twice daily.	1 drop of AGN-195263 vehicle (placebo) instilled in each eye twice daily.
Measure Participants	54	56	53	49
Number [Percentage of Patients]	46.3	33.9	32.1	42.9

2. Secondary Outcome

Title	Percentage of Maximum Meibum Quality Score (MMQS) Responders in the Study Eye
Description	The MQS is assessed based on Mathers' meibum quality secretion grading 4-point scale where: 0 = Clear excreta or clear with small particles (normal viscosity), 1 = Opaque excreta with normal viscosity, 2 = Opaque excreta with increased viscosity (gel-like), and 3 = Secretions retain shape (or secretions do not express but a toothpaste-like substance can be seen at the opening of the orifice). MMQS is calculated for each eye as the maximum of the meibum quality scores of the expressible glands within the 6 central glands of the lower eyelids. A patient is considered to be an MMQS responder at a postrandomization visit if the MMQS in the study eye is 0 or 1 (indicating normal viscosity) at that visit.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat: all randomized and treated patients who have values for meibum quality score at randomization, at least one postrandomization visit, and data at the noted time point

Arm/Group Title	AGN-195263 0.1%	AGN-195263 0.03%	AGN-195263 0.01%	AGN-195263 Vehicle
Arm/Group Description	1 drop of AGN-195263 0.1% instilled in each eye twice daily.	1 drop of AGN-195263 0.03% instilled in each eye twice daily.	1 drop of AGN-195263 0.01% instilled in each eye twice daily.	1 drop of AGN-195263 vehicle (placebo) instilled in each eye twice daily.
Measure Participants	54	56	53	49
Number [Percentage of Patients]	20.4	23.2	15.1	22.4

3. Secondary Outcome

Title	Percentage of Complete Overall Ocular Discomfort Responders
Description	Ocular symptoms of blurred vision, burning, dryness, eye pain, light sensitivity, itching, and foreign body sensation are assessed by the patient on a 5-point scale ranging from 0 = none to 4 = very severe. A patient is considered a complete overall ocular discomfort responder if the overall ocular discomfort score is 0 (indicating no overall ocular discomfort) at that visit.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat: all randomized and treated patients who have values for meibum quality score at randomization, at least one postrandomization visit, and data at the noted time point

Arm/Group Title	AGN-195263 0.1%	AGN-195263 0.03%	AGN-195263 0.01%	AGN-195263 Vehicle
Arm/Group Description	1 drop of AGN-195263 0.1% instilled in each eye twice daily.	1 drop of AGN-195263 0.03% instilled in each eye twice daily.	1 drop of AGN-195263 0.01% instilled in each eye twice daily.	1 drop of AGN-195263 vehicle (placebo) instilled in each eye twice daily.
Measure Participants	55	56	54	51
Number [Percentage of Patients]	20.0	19.6	14.8	9.8

Adverse Events

Adverse Event Reporting Description	The Safety Population is used to assess adverse events and serious adverse events and consists of all patients who received at least one dose of study treatment.
Arm/Group Title	AGN-195263 0.1%		AGN-195263 0.03%		AGN-195263 0.01%		AGN-195263 Vehicle
Arm/Group Description	1 drop of AGN-195263 0.1% instilled in each eye twice daily.		1 drop of AGN-195263 0.03% instilled in each eye twice daily.		1 drop of AGN-195263 0.01% instilled in each eye twice daily.		1 drop of AGN-195263 vehicle (placebo) instilled in each eye twice daily.
All Cause Mortality
	AGN-195263 0.1%		AGN-195263 0.03%		AGN-195263 0.01%		AGN-195263 Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	AGN-195263 0.1%		AGN-195263 0.03%		AGN-195263 0.01%		AGN-195263 Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/57 (1.8%)		4/58 (6.9%)		3/59 (5.1%)		0/58 (0%)
Cardiac disorders
Atrial fibrillation	0/57 (0%)		1/58 (1.7%)		0/59 (0%)		0/58 (0%)
Angina pectoris	0/57 (0%)		0/58 (0%)		1/59 (1.7%)		0/58 (0%)
General disorders
Gait disturbance	1/57 (1.8%)		0/58 (0%)		0/59 (0%)		0/58 (0%)
Musculoskeletal and connective tissue disorders
Muscle spasms	0/57 (0%)		1/58 (1.7%)		0/59 (0%)		0/58 (0%)
Spinal osteoarthritis	0/57 (0%)		0/58 (0%)		1/59 (1.7%)		0/58 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone cancer	0/57 (0%)		1/58 (1.7%)		0/59 (0%)		0/58 (0%)
Lung carcinoma cell type unspecified stage IV	0/57 (0%)		1/58 (1.7%)		0/59 (0%)		0/58 (0%)
Breast cancer	0/57 (0%)		0/58 (0%)		1/59 (1.7%)		0/58 (0%)
Nervous system disorders
Migraine	0/57 (0%)		1/58 (1.7%)		0/59 (0%)		0/58 (0%)
Other (Not Including Serious) Adverse Events
	AGN-195263 0.1%		AGN-195263 0.03%		AGN-195263 0.01%		AGN-195263 Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/57 (12.3%)		6/58 (10.3%)		3/59 (5.1%)		7/58 (12.1%)
Eye disorders
Eye pruritus	3/57 (5.3%)		2/58 (3.4%)		2/59 (3.4%)		0/58 (0%)
Foreign body sensation in eyes	3/57 (5.3%)		1/58 (1.7%)		0/59 (0%)		0/58 (0%)
Lacrimation increased	3/57 (5.3%)		0/58 (0%)		1/59 (1.7%)		0/58 (0%)
Infections and infestations
Upper respiratory tract infection	1/57 (1.8%)		0/58 (0%)		1/59 (1.7%)		4/58 (6.9%)
Investigations
Prostatic specific antigen increased	1/18 (5.6%)		0/19 (0%)		0/20 (0%)		2/19 (10.5%)
Skin and subcutaneous tissue disorders
Alopecia	0/57 (0%)		4/58 (6.9%)		0/59 (0%)		1/58 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.