STRIDE 1: Safety and Efficacy of KPI-121 in Subjects With Dry Eye Disease

• Sponsor: Kala Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02813265
• Collaborator: (none)
• Enrollment: 918
• Locations: 60
• Arms: 2
• Actual Duration (Months): 16
• Patients Per Site: 15.3
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The primary purpose of this study is to determine the efficacy and safety of KPI-121 0.25% ophthalmic suspension compared to vehicle (placebo) in subjects who have a documented clinical diagnosis of dry eye disease. The product will be studied over 14 days, with 1-2 drops instilled in each eye four times daily (QID).

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes; Keratoconjunctivitis Sicca	Drug: KPI-121 0.25% Ophthalmic Suspension; Drug: Vehicle of KPI-121 0.25% Ophthalmic Suspension	Phase 3

Detailed Description

This is a Phase 3, multi-center, double-masked, randomized, vehicle-controlled, parallel-group study designed to evaluate the safety and efficacy of KPI-121 0.25% ophthalmic suspension versus vehicle in subjects with dry eye disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 918 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Double-Masked, Randomized, Controlled Study of KPI-121 0.25% Ophthalmic Suspension Compared to Vehicle in Subjects With Dry Eye Disease
• Actual Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: KPI-121 0.25% Ophthalmic Suspension	Drug: KPI-121 0.25% Ophthalmic Suspension; Other Names: Loteprednol etabonate
Placebo Comparator: Vehicle of KPI-121 0.25% Ophthalmic Suspension	Drug: Vehicle of KPI-121 0.25% Ophthalmic Suspension; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15) [Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)]

   Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.

2. Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) [Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)]

   Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.

3. Change From Baseline/Visit 2 (Day 1) in Corneal Fluorescein Staining Score at Visit 4 (Day 15) [Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)]

   Comparison of mean corneal fluorescein staining between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe.

4. Change From Baseline/Visit 2 (Day 1) Ocular Discomfort Severity at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort [Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)]

   Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse, in a sub-group of participants with more severe ocular discomfort at baseline.

Secondary Outcome Measures

1. Change in Conjunctival Hyperemia Scores at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort at Baseline (Day 1) [Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)]

   Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.

2. Proportion of Subjects With ≥1 Improvement in Conjunctival Hyperemia at Visit 4 (Day 15) [Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)]

   Proportion of subjects with ≥1 improvement from baseline in conjunctival hyperemia scores. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.

3. Change From Baseline/Visit 2 (Day 1) Conjunctival Hyperemia Scores at Visit 4 (Day 15) for the Mean of All Regions (Nasal, Temporal, Frontal) [Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)]

   Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.

4. Change in Ocular Discomfort Severity Scores Prior to Visit 3 (Day 8) Minus the Mean of the Scores to Baseline/Visit 2 (Day 1) [Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)]

   Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.

5. Change in Ocular Discomfort Severity Scores Prior to Visit 3 (Day 8) Minus Baseline/Visit 2 (Day 1) in the Subgroup of Participants With More Severe Ocular Discomfort. [Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)]

   Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.

6. Change in Ocular Discomfort Severity Scores on Day 4 (Diary) Minus Baseline/Visit 2 (Day 1) [Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)]

   Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.

7. Change in Ocular Discomfort Severity Scores on Day 4 Day 4 (Diary) Minus Baseline/Visit 2 (Day 1) in the Subgroup of Participants With More Severe Ocular Discomfort [Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)]

   Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse, in a sub-group of participants with more severe ocular discomfort at baseline.

8. Change From Baseline/Visit 2 (Day 1) in Conjunctival Hyperemia Scores With a Day 1 Conjunctival Hyperemia Score of ≥ 2 in the Subgroup of Participants With More Severe Ocular Discomfort [Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)]

   Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale in a sub-group of participants with more severe ocular discomfort at baseline.. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.

9. Subjects With a Grade of 0 in Conjunctival Hyperemia Score at Visit 4 (Day 15) [Visit 4 (Day 15)]

   Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have a documented clinical diagnosis of dry eye disease in both eyes

Exclusion Criteria:

• Known hypersensitivity or contraindication to the investigational product(s) or components

• History of glaucoma, Intraocular Pressure (IOP) >21 mmHg at the screening or randomization visits, or being treated for glaucoma in either eye.

• Diagnosis of: ongoing ocular infection; severe/serious ocular condition that in judgment of Investigator could confound study assessments or limit compliance; or have been exposed to an investigational drug within 30 days prior to screening.

• In the opinion of the Investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cornea and Cataract Consultants of Arizona	Phoenix	Arizona	United States	85032
2	Schwartz Laser Eye Center	Scottsdale	Arizona	United States	85260
3	Eyecare Arkansas, P.A.	Little Rock	Arkansas	United States	72205
4	Little Rock Eye Clinic, LLP	Little Rock	Arkansas	United States	72205
5	Sall Research Medical Center	Artesia	California	United States	90701
6	Orange County Ophthalmology Medical Group	Garden Grove	California	United States	92843
7	United Medical Research Institute	Inglewood	California	United States	90301
8	North Valley Eye Medical Group	Mission Hills	California	United States	91345
9	Montebello Medical Center, Inc.	Montebello	California	United States	90640
10	LoBue Laser and Eye Medical Center	Murrieta	California	United States	92562
11	Eye Research Foundation	Newport Beach	California	United States	92663
12	Pendleton Eye Center	Oceanside	California	United States	92056
13	North Bay Eye Associates, Inc.	Petaluma	California	United States	94954
14	Martel Eye Medical Group	Rancho Cordova	California	United States	95670
15	Sacramento Eye Consultants	Sacramento	California	United States	95815
16	Eye Center of Northern Colorado, PC	Fort Collins	Colorado	United States	80525
17	Corneal Consultants of Colorado	Littleton	Colorado	United States	80209
18	The Eye Center of Southern CT, P.C.	Hamden	Connecticut	United States	06518
19	Florida Eye Microsurgical Institute, Inc.	Boynton Beach	Florida	United States	33426
20	Eye Associates of Fort Myers	Fort Myers	Florida	United States	33901
21	Shettle Eye Research, Inc.	Largo	Florida	United States	33773
22	Atlantic Eye Center	Palm Coast	Florida	United States	32137
23	The Eye Center of North Florida	Panama City	Florida	United States	32405
24	Dixon Eye Care	Albany	Georgia	United States	31701
25	Jacksoneye, S. C.	Lake Villa	Illinois	United States	60046
26	Midwest Cornea Associates, LLC	Indianapolis	Indiana	United States	46290
27	Stiles EyeCare Excellence and Glaucoma Institute	Overland Park	Kansas	United States	66213
28	Clinical Eye Research of Boston	Winchester	Massachusetts	United States	01890
29	Chu Vision Institute	Bloomington	Minnesota	United States	55420
30	Lifelong Vision Foundation at Pepose Vision Institute	Chesterfield	Missouri	United States	63017
31	Ophthalmology Associates	Saint Louis	Missouri	United States	63131
32	Ophthalmology Consultants, Ltd.	Saint Louis	Missouri	United States	63131
33	Wellish Vision Institute	Las Vegas	Nevada	United States	89119
34	Matossian Eye Associates	Pennington	New Jersey	United States	08534
35	Rochester Ophthalmological Group, PC	Rochester	New York	United States	14618
36	Cornea Consultants of Albany	Slingerlands	New York	United States	12159
37	South Shore Eye Center, LLP	Wantagh	New York	United States	11793
38	Mundorf Eye Center	Charlotte	North Carolina	United States	28204
39	Firozvi Research, LLC / North Carolina Eye, Ear, Nose & Throat	Durham	North Carolina	United States	27704
40	Eyecare Center	Raleigh	North Carolina	United States	27603
41	Bergstrom Eye Research	Fargo	North Dakota	United States	58103
42	Abrams Eye Center	Cleveland	Ohio	United States	44115
43	Opthalamic Surgeons & Consultants of Ohio	Columbus	Ohio	United States	43215
44	Apex Eye	Mason	Ohio	United States	45040
45	Roseburg Research Associates, LLC	Roseburg	Oregon	United States	97471
46	Scott & Christie and Associates, PC	Cranberry Township	Pennsylvania	United States	16066
47	Conestoga Eye	Lancaster	Pennsylvania	United States	17601
48	UPMC Eye Center	Pittsburgh	Pennsylvania	United States	15213
49	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701
50	Total Eye Care, PA	Memphis	Tennessee	United States	38119
51	Hill Country Eye Center	Cedar Park	Texas	United States	78613
52	Houston Eye Associates	Houston	Texas	United States	77025
53	The Eye Clinic of Texas, Affiliate of Houston Eye Associates	League City	Texas	United States	77573
54	Lake Travis Eye and Laser Center	Leander	Texas	United States	78641
55	Eye Clinics of South Texas	San Antonio	Texas	United States	78209
56	R and R Eye Research, LLC	San Antonio	Texas	United States	78229
57	Keystone Research - Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240
58	Tanner Clinic	Layton	Utah	United States	84041
59	See Clearly Vision	McLean	Virginia	United States	22102
60	Virginia Eye Consultants	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Kala Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 6, 2017

More Information

Publications

None provided.

• Responsible Party: Kala Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02813265
• Other Study ID Numbers: KPI-121-C-006
• First Posted: Jun 24, 2016
• Last Update Posted: Feb 3, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Kala Pharmaceuticals, Inc.: Ocular Discomfort; Pain; Corticosteroid; Hyperemia; Dry Eye
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Keratoconjunctivitis; Loteprednol Etabonate

Study Results

Participant Flow

Pre-assignment Detail	918 subjects were randomized, 3 of which were not included in any analysis population as they had participated in more than one study. The data for the second-participation for these 3 individuals were not included in any analysis population as agreed upon with the FDA.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Period Title: Overall Study
STARTED	459	456
COMPLETED	455	453
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension	Total
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension	Total of all reporting groups
Overall Participants	459	456	915
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.1 (15.41)	58.3 (14.66)	58.2 (15.03)
Sex: Female, Male (Count of Participants)
Female	367 80%	359 78.7%	726 79.3%
Male	92 20%	97 21.3%	189 20.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.4%	0 0%	2 0.2%
Asian	18 3.9%	18 3.9%	36 3.9%
Native Hawaiian or Other Pacific Islander	1 0.2%	1 0.2%	2 0.2%
Black or African American	69 15%	71 15.6%	140 15.3%
White	362 78.9%	361 79.2%	723 79%
More than one race	1 0.2%	1 0.2%	2 0.2%
Unknown or Not Reported	6 1.3%	4 0.9%	10 1.1%
Region of Enrollment (participants) [Number]
United States	459 100%	456 100%	915 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15)
Description	Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	452	451
Mean (Standard Deviation) [score on a scale]	-0.4049 (0.65062)	-0.1574 (0.60704)

2. Primary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15)
Description	Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	455	452
Mean (Standard Deviation) [score on a scale]	-14.53 (20.636)	-9.16 (17.924)

3. Primary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Corneal Fluorescein Staining Score at Visit 4 (Day 15)
Description	Comparison of mean corneal fluorescein staining between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	455	452
Mean (Standard Deviation) [score on a scale]	-0.5 (0.84)	-0.4 (0.79)

4. Primary Outcome

Title	Change From Baseline/Visit 2 (Day 1) Ocular Discomfort Severity at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort
Description	Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse, in a sub-group of participants with more severe ocular discomfort at baseline.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

Sub-group of Intent to Treat population with more severe ocular discomfort minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	233	238
Mean (Standard Deviation) [score on a scale]	-16.67 (21.937)	-10.76 (18.037)

5. Secondary Outcome

Title	Change in Conjunctival Hyperemia Scores at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort at Baseline (Day 1)
Description	Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

Sub-group of Intent to Treat population with more severe ocular discomfort minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	256	264
Mean (Standard Deviation) [score on a scale]	-0.4648 (0.66770)	-0.2045 (0.62567)

6. Secondary Outcome

Title	Proportion of Subjects With ≥1 Improvement in Conjunctival Hyperemia at Visit 4 (Day 15)
Description	Proportion of subjects with ≥1 improvement from baseline in conjunctival hyperemia scores. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	452	451
Count of Participants [Participants]	189 41.2%	98 21.5%

7. Secondary Outcome

Title	Change From Baseline/Visit 2 (Day 1) Conjunctival Hyperemia Scores at Visit 4 (Day 15) for the Mean of All Regions (Nasal, Temporal, Frontal)
Description	Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	453	450
Mean (Standard Deviation) [score on a scale]	-0.2980 (0.59018)	-0.0421 (0.51921)

8. Secondary Outcome

Title	Change in Ocular Discomfort Severity Scores Prior to Visit 3 (Day 8) Minus the Mean of the Scores to Baseline/Visit 2 (Day 1)
Description	Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)

Outcome Measure Data

Analysis Population Description

Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	457	455
Mean (Standard Deviation) [score on a scale]	-8.12 (16.880)	-4.81 (14.851)

9. Secondary Outcome

Title	Change in Ocular Discomfort Severity Scores Prior to Visit 3 (Day 8) Minus Baseline/Visit 2 (Day 1) in the Subgroup of Participants With More Severe Ocular Discomfort.
Description	Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)

Outcome Measure Data

Analysis Population Description

Sub-group of Intent to Treat population with more severe ocular discomfort minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	258	263
Mean (Standard Deviation) [score on a scale]	-9.90 (17.835)	-6.38 (15.289)

10. Secondary Outcome

Title	Change in Ocular Discomfort Severity Scores on Day 4 (Diary) Minus Baseline/Visit 2 (Day 1)
Description	Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)

Outcome Measure Data

Analysis Population Description

Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	455	452
Mean (Standard Deviation) [score on a scale]	-6.60 (16.710)	-3.20 (15.125)

11. Secondary Outcome

Title	Change in Ocular Discomfort Severity Scores on Day 4 Day 4 (Diary) Minus Baseline/Visit 2 (Day 1) in the Subgroup of Participants With More Severe Ocular Discomfort
Description	Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse, in a sub-group of participants with more severe ocular discomfort at baseline.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)

Outcome Measure Data

Analysis Population Description

Sub-group of Intent to Treat population with more severe ocular discomfort minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	256	261
Mean (Standard Deviation) [score on a scale]	-8.48 (17.412)	-5.20 (14.903)

12. Secondary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Conjunctival Hyperemia Scores With a Day 1 Conjunctival Hyperemia Score of ≥ 2 in the Subgroup of Participants With More Severe Ocular Discomfort
Description	Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale in a sub-group of participants with more severe ocular discomfort at baseline.. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.
Time Frame	Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

Sub-group of Intent to Treat population with more severe ocular discomfort minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	379	379
Mean (Standard Deviation) [score on a scale]	-0.47 (0.631)	-0.22 (0.577)

13. Secondary Outcome

Title	Subjects With a Grade of 0 in Conjunctival Hyperemia Score at Visit 4 (Day 15)
Description	Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe
Time Frame	Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Measure Participants	453	451
Count of Participants [Participants]	27 5.9%	16 3.5%

Adverse Events

Time Frame	Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension		Vehicle of KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	Participants randomized to KPI-121 0.25% Ophthalmic Suspension		Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
All Cause Mortality
	KPI-121 0.25% Ophthalmic Suspension		Vehicle of KPI-121 0.25% Ophthalmic Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/459 (0%)		0/456 (0%)
Serious Adverse Events
	KPI-121 0.25% Ophthalmic Suspension		Vehicle of KPI-121 0.25% Ophthalmic Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/459 (0%)		0/456 (0%)
Other (Not Including Serious) Adverse Events
	KPI-121 0.25% Ophthalmic Suspension		Vehicle of KPI-121 0.25% Ophthalmic Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/459 (14.4%)		62/456 (13.6%)
Eye disorders
Eye Irritation	5/459 (1.1%)		7/456 (1.5%)
Blepharitis	3/459 (0.7%)		0/456 (0%)
Lacrimination increased	3/459 (0.7%)		2/456 (0.4%)
Conjunctival hyperemia	2/459 (0.4%)		4/456 (0.9%)
Eye Pain	2/459 (0.4%)		1/456 (0.2%)
Foreign Body Sensation	2/459 (0.4%)		4/456 (0.9%)
Conjunctival vascular disorder	1/459 (0.2%)		0/456 (0%)
Eye discharge	1/459 (0.2%)		0/456 (0%)
Eye Pruritus	1/459 (0.2%)		4/456 (0.9%)
Eyelid margin crusting	1/459 (0.2%)		2/456 (0.4%)
Eyelid ptosis	1/459 (0.2%)		0/456 (0%)
Trichiasis	1/459 (0.2%)		0/456 (0%)
Vision Blurred	1/459 (0.2%)		2/456 (0.4%)
Vitreous detachment	1/459 (0.2%)		0/456 (0%)
Blepharospasm	0/459 (0%)		1/456 (0.2%)
Keratitis	0/459 (0%)		1/456 (0.2%)
Ocular hyperaemia	0/459 (0%)		1/456 (0.2%)
Photophobia	0/459 (0%)		1/456 (0.2%)
Punctate keratitis	0/459 (0%)		1/456 (0.2%)
Gastrointestinal disorders
hypoaesthesia oral	1/459 (0.2%)		0/456 (0%)
Toothache	1/459 (0.2%)		0/456 (0%)
Gingival bleeding	0/459 (0%)		1/456 (0.2%)
General disorders
Installation site pain	28/459 (6.1%)		28/456 (6.1%)
Instillation site foreign body sensation	2/459 (0.4%)		0/456 (0%)
Instillation site lacrimation	1/459 (0.2%)		0/456 (0%)
Instillation site pruritus	1/459 (0.2%)		3/456 (0.7%)
Installation site discomfort	0/459 (0%)		1/456 (0.2%)
Installation site reaction	0/459 (0%)		1/456 (0.2%)
Immune system disorders
Hypersensitivity	1/459 (0.2%)		0/456 (0%)
Infections and infestations
Pneumonia	1/459 (0.2%)		0/456 (0%)
Sinusitis	1/459 (0.2%)		0/456 (0%)
Upper respiratory tract infection	1/459 (0.2%)		2/456 (0.4%)
Bronchitis	0/459 (0%)		1/456 (0.2%)
Conjunctivitis	0/459 (0%)		1/456 (0.2%)
Herpes zoster	0/459 (0%)		1/456 (0.2%)
Nasopharyngitis	0/459 (0%)		3/456 (0.7%)
Urinary tract infection	0/459 (0%)		1/456 (0.2%)
Injury, poisoning and procedural complications
Arthropod bite	1/459 (0.2%)		0/456 (0%)
Ligament Sprain	1/459 (0.2%)		1/456 (0.2%)
Fall	0/459 (0%)		1/456 (0.2%)
Investigations
Intraocular pressure increased	3/459 (0.7%)		1/456 (0.2%)
Musculoskeletal and connective tissue disorders
Spinal Column Stenosis	1/459 (0.2%)		0/456 (0%)
Nervous system disorders
Headache	2/459 (0.4%)		1/456 (0.2%)
Hypoaesthesia	1/459 (0.2%)		0/456 (0%)
Nerve Compression	1/459 (0.2%)		0/456 (0%)
Sinus Headache	1/459 (0.2%)		1/456 (0.2%)
Psychiatric disorders
Anxiety	0/459 (0%)		1/456 (0.2%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	1/459 (0.2%)		0/456 (0%)
Dysphonia	0/459 (0%)		1/456 (0.2%)
Pulmonary congestion	0/459 (0%)		1/456 (0.2%)
Sneezing	0/459 (0%)		1/456 (0.2%)
Skin and subcutaneous tissue disorders
Dermatitis Contact	1/459 (0.2%)		0/456 (0%)
Eccymosis	1/459 (0.2%)		1/456 (0.2%)
Rash	1/459 (0.2%)		1/456 (0.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The agreement between the Principal Investigator and the Sponsor restricts the PI's rights to discuss or publish trial results until after the first to occur of the following: (a) publication of such multi-center clinical trial results; (b) notification by sponsor that such a multi-center clinical trial submission is no longer planned; or ( c) the eighteen ( 18) month anniversary of the completion, abandonment or termination of such multi-center clinical trial.