STRIDE 2: Safety and Efficacy of KPI-121 Compared to Placebo in Subjects With Dry Eye Disease

• Sponsor: Kala Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02819284
• Collaborator: (none)
• Enrollment: 909
• Locations: 62
• Arms: 2
• Actual Duration (Months): 15
• Patients Per Site: 14.7
• 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: 909 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: Sep 1, 2017
• Actual Study Completion Date: Sep 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) - Visit 4 (Day 15)]

   Comparison of mean change from baseline for bulbar conjunctival hyperemia in the study eye 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) - Visit 4 (Day 15)]

   Comparison of mean ocular discomfort 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.

Secondary Outcome Measures

1. Proportion of Subjects With ≥ 1 Unit Improvement From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia Worst Region at Visit 4 (Day 15) [Baseline/Visit 2 (Day 1) - Visit 4 (Day 15)]

   Proportion of subjects with ≥1 improvement from baseline in conjunctival hyperemia scores in the study eye. 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 Scores at Visit 3 (Day 8) [Baseline/Visit 2 (Day 1) - Visit 3 (Day 8)]

   Comparison of ocular discomfort scores 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 using 3-day mean scores.

3. Change From Baseline/Week 2 (Day 1) in Ocular Discomfort Scores to Day 4 [Baseline/Visit 2 (Day 1) - Day 4]

   Comparison of mean ocular discomfort 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.

4. Change From Baseline/Week 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) in a Subgroup [Baseline/Visit 2 (Day 1) - Visit 4 (Day 15)]

   Comparison of mean ocular discomfort 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, using 3 day means.

5. Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity Scores at Day 3 (Diary) [Baseline/Visit 2 (Day 1) - Day 3]

   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 From Baseline/Visit 2 (Day 1) in Eye Dryness Scores at Visit 4 (Day 15) [Baseline/Visit 2 (Day 1) - Visit 4 (Day 15)]

   Comparison of mean eye dryness 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 From Baseline/Visit 2 (Day 1) in Eye Dryness Scores at Visit 3 (Day 8) [Baseline/Visit 2 (Day 1) - Visit 3 (Day 8)]

   Comparison of mean eye dryness 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.

8. Ocular Discomfort Severity Scores on Day 2 (Diary) Minus Baseline/Visit 2 (Day 1) [Baseline/Visit 2 (Day 1) - Day 1]

   Comparison of mean ocular discomfort 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.

9. Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Frequency Scores at Visit 4 (Day 15) [Baseline/Visit 2 (Day 1) - Visit 4 (Day 15)]

   Comparison of mean ocular discomfort frequency 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.

10. Change From Baseline/Visit 2 (Day 1) in Subject-rated Ocular Discomfort Frequency Scores at Visit 3 (Day 8) [Baseline/Visit 2 (Day 1) - Visit 3 (Day 8)]

    Comparison of mean ocular discomfort frequency 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.

11. Change From Baseline/Visit 2 (Day 1) in Inferior Corneal Fluorescein Staining Score at Visit 4 (Day 15) [Baseline/Visit 2 (Day 1) - Visit 4 (Day 15)]

    Comparison of mean corneal fluorescein staining in the study eye 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.

12. Change From Baseline/Visit 2 (Day 1) in Nasal Corneal Fluorescein Staining Score at Visit 4 (Day 15) [Baseline/Visit 2 (Day 1) - Visit 4 (Day 15)]

    Comparison of mean nasal corneal fluorescein staining in the study eye 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.

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, 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	UAB School of Optometry	Birmingham	Alabama	United States	35294-0010
2	Arizona Eye Center	Chandler	Arizona	United States	85225
3	NEA Baptist Clinic	Jonesboro	Arkansas	United States	72401
4	Sall Research Medical Center	Artesia	California	United States	90701
5	Milton M. Hom, OD, FAAO	Azusa	California	United States	91702
6	Family Eye Care Center	Campbell	California	United States	95008
7	Orange County Ophthalmology	Garden Grove	California	United States	92843
8	Lugene Eye Institute	Glendale	California	United States	91204
9	The Gavin Herbert Eye Institute	Irvine	California	United States	92697-4375
10	Macy Eye Center	Los Angeles	California	United States	90048
11	Advanced Vision Care	Los Angeles	California	United States	90067
12	North Valley Eye Medical Group	Mission Hills	California	United States
13	Eye Research Foundation	Newport Beach	California	United States	92663
14	Arch Health Partners	Poway	California	United States	92064
15	Martel Eye Medical Group	Rancho Cordova	California	United States	95670
16	Shasta Eye Medical Group, Inc	Redding	California	United States	96002
17	West Coast Eye Care Associates	San Diego	California	United States	92115
18	Wolstan & Goldberg Eye Associates	Torrance	California	United States	90505
19	Michael K Tran, M.D., Inc.	Westminster	California	United States	92683
20	Hernando Eye Institute	Brooksville	Florida	United States	34613
21	Central Florida Eye Associates	Lakeland	Florida	United States	33805
22	Shettle Eye Research, Inc	Largo	Florida	United States	33773
23	International Eye Associates PA	Ormond Beach	Florida	United States	32174
24	Perez Eye Center/International Research Center	Tampa	Florida	United States	33603
25	Eye Care Centers Management, Inc. (Clayton Eye Center)	Morrow	Georgia	United States	30260
26	Chicago Cornea Consultants, Ltd.	Hoffman Estates	Illinois	United States	60169
27	Price Vision Group	Indianapolis	Indiana	United States	46260
28	John-Kenyon American Eye Institute	New Albany	Indiana	United States	47150
29	Cincinnati Eye Institute	Edgewood	Kentucky	United States	41017
30	Koffler Vision Group	Lexington	Kentucky	United States	40509
31	The Eye Care Institute	Louisville	Kentucky	United States	40206
32	Taustine Eye Center	Louisville	Kentucky	United States	40217
33	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
34	Minnesota Eye Consultants, PA	Bloomington	Minnesota	United States	55431
35	Tauber Eye Center	Kansas City	Missouri	United States	64111
36	Tekwani Vision Center	Saint Louis	Missouri	United States	63128
37	Comprehensive Eye Care, Ltd. / Vision Research Institute, LLC	Washington	Missouri	United States	63090
38	Abrams Eye Institute	Las Vegas	Nevada	United States	89148
39	Raymond Fong, MDPC	New York	New York	United States	10013
40	Ophthalmic Consultants of Long Island	Rockville Centre	New York	United States	11570
41	Cornerstone Eye Care	High Point	North Carolina	United States	27262
42	James D Branch MD	Winston-Salem	North Carolina	United States	27101
43	Comprehensive Eye Care of Central Ohio	Westerville	Ohio	United States	43082
44	Drs. Fine, Hoffman & Sims, LLC	Eugene	Oregon	United States	97401
45	Scott & Christie and Associates, PC	Cranberry Township	Pennsylvania	United States	16066
46	Eye Care Specialists	Kingston	Pennsylvania	United States	18704
47	Bucci Laser Vision Institute	Wilkes-Barre	Pennsylvania	United States	18702
48	Chattanooga Eye Institute, P.C.	Chattanooga	Tennessee	United States	37411
49	Total Eye Care, PA	Memphis	Tennessee	United States	38119
50	Toyos Clinic	Nashville	Tennessee	United States	37215
51	Texan Eye, PA / Keystone Research, Ltd	Austin	Texas	United States	78731
52	The Cataract and Glaucoma Center	El Paso	Texas	United States	79902
53	Houston Eye Associates	Houston	Texas	United States	77024
54	Advanced Laser Vision & Surgical Institute, Intouch Clinical Research Center	Houston	Texas	United States	77034
55	Whitsett Vision Group	Houston	Texas	United States	77055
56	The Ocular Surface Institute (TOSI), University of Houston	Houston	Texas	United States	77204
57	Brazosport Eye Institute	Lake Jackson	Texas	United States	77566
58	Kozlovsky Delay & Winter Eye Consultants, LLC	San Antonio	Texas	United States	78230
59	Hoopes Vision	Draper	Utah	United States	84020
60	Virginia Eye Consultants	Norfolk	Virginia	United States	23502
61	Spokane Eye Clinical Research	Spokane	Washington	United States	99204
62	Regional Eye Associates	Morgantown	West Virginia	United States	26505

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: NCT02819284
• Other Study ID Numbers: KPI-121-C-007
• First Posted: Jun 30, 2016
• Last Update Posted: Jan 5, 2021
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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	909 subjects were randomized, 4 of which were not included in any analysis population as agreed upon with the FDA. 3 individuals had participated in more than one study therefore the data for their second-participation were not included and 1 individual did not receive treatment.

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	452	453
COMPLETED	447	448
NOT COMPLETED	5	5

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	452	453	905
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (14.48)	59.3 (15.01)	59.2 (14.74)
Sex: Female, Male (Count of Participants)
Female	332 73.5%	354 78.1%	686 75.8%
Male	120 26.5%	99 21.9%	219 24.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	39 8.6%	35 7.7%	74 8.2%
Native Hawaiian or Other Pacific Islander	1 0.2%	1 0.2%	2 0.2%
Black or African American	58 12.8%	54 11.9%	112 12.4%
White	345 76.3%	352 77.7%	697 77%
More than one race	2 0.4%	2 0.4%	4 0.4%
Unknown or Not Reported	7 1.5%	9 2%	16 1.8%
Region of Enrollment (participants) [Number]
United States	452 100%	453 100%	905 100%

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 change from baseline for bulbar conjunctival hyperemia in the study eye 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) - 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	446	447
Mean (Standard Deviation) [score on a scale]	-0.3812 (0.60560)	-0.2371 (0.62256)

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 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) - 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	445	444
Mean (Standard Deviation) [score on a scale]	-11.14 (19.901)	-9.24 (17.002)

3. Secondary Outcome

Title	Proportion of Subjects With ≥ 1 Unit Improvement From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia Worst Region at Visit 4 (Day 15)
Description	Proportion of subjects with ≥1 improvement from baseline in conjunctival hyperemia scores in the study eye. 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) - 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	446	447
Count of Participants [Participants]	171 37.8%	127 28%

4. Secondary Outcome

Title	Change From Baseline/ Visit 2 (Day 1) in Ocular Discomfort Severity Scores at Visit 3 (Day 8)
Description	Comparison of ocular discomfort scores 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 using 3-day mean scores.
Time Frame	Baseline/Visit 2 (Day 1) - 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	449	451
Mean (Standard Deviation) [score on a scale]	-6.92 (15.541)	-4.86 (14.911)

5. Secondary Outcome

Title	Change From Baseline/Week 2 (Day 1) in Ocular Discomfort Scores to Day 4
Description	Comparison of mean ocular discomfort 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) - Day 4

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	447	449
Mean (Standard Deviation) [score on a scale]	-5.09 (14.523)	-4.10 (14.894)

6. Secondary Outcome

Title	Change From Baseline/Week 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) in a Subgroup
Description	Comparison of mean ocular discomfort 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, using 3 day means.
Time Frame	Baseline/Visit 2 (Day 1) - 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	254	257
Mean (Standard Deviation) [score on a scale]	-12.45 (20.352)	-9.45 (17.489)

7. Secondary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity Scores at Day 3 (Diary)
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) - Day 3

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	451	449
Mean (Standard Deviation) [score on a scale]	-3.28 (13.697)	-3.15 (14.126)

8. Secondary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Eye Dryness Scores at Visit 4 (Day 15)
Description	Comparison of mean eye dryness 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) - 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	447	445
Mean (Standard Deviation) [score on a scale]	-14.0 (22.78)	-11.5 (20.53)

9. Secondary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Eye Dryness Scores at Visit 3 (Day 8)
Description	Comparison of mean eye dryness 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) - 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	442	447
Mean (Standard Deviation) [score on a scale]	-9.6 (18.66)	-8.0 (18.94)

10. Secondary Outcome

Title	Ocular Discomfort Severity Scores on Day 2 (Diary) Minus Baseline/Visit 2 (Day 1)
Description	Comparison of mean ocular discomfort 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) - Day 1

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	451	447
Mean (Standard Deviation) [score on a scale]	-2.33 (13.707)	-2.43 (13.364)

11. Secondary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Frequency Scores at Visit 4 (Day 15)
Description	Comparison of mean ocular discomfort frequency 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) - 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	445	444
Mean (Standard Deviation) [score on a scale]	-10.20 (20.722)	-8.38 (17.974)

12. Secondary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Subject-rated Ocular Discomfort Frequency Scores at Visit 3 (Day 8)
Description	Comparison of mean ocular discomfort frequency 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) - 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	449	451
Mean (Standard Deviation) [score on a scale]	-5.96 (16.133)	-4.42 (16.133)

13. Secondary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Inferior Corneal Fluorescein Staining Score at Visit 4 (Day 15)
Description	Comparison of mean corneal fluorescein staining in the study eye 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) - 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	448	448
Mean (Standard Deviation) [score on a scale]	-0.6 (0.86)	-0.5 (0.83)

14. Secondary Outcome

Title	Change From Baseline/Visit 2 (Day 1) in Nasal Corneal Fluorescein Staining Score at Visit 4 (Day 15)
Description	Comparison of mean nasal corneal fluorescein staining in the study eye 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) - 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	448	448
Mean (Standard Deviation) [score on a scale]	-0.6 (0.86)	-0.4 (0.83)

Adverse Events

Time Frame	Adverse events were collected from Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Adverse Event Reporting Description	Both treatment-related and non-treatment-related adverse events are reported here.
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	0/452 (0%)		0/453 (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	3/452 (0.7%)		0/453 (0%)
Gastrointestinal disorders
diverticulum intestinal	1/452 (0.2%)	1	0/453 (0%)	0
Musculoskeletal and connective tissue disorders
hip fracture	1/452 (0.2%)	1	0/453 (0%)	0
intervertebral disc protrusion	1/452 (0.2%)	1	0/453 (0%)	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	57/452 (12.6%)		44/453 (9.7%)
Ear and labyrinth disorders
Ear pain	1/452 (0.2%)		0/453 (0%)
Eye disorders
Eye pruritus	3/452 (0.7%)		4/453 (0.9%)
Conjunctival hyperaemia	2/452 (0.4%)		3/453 (0.7%)
Eye irritation	2/452 (0.4%)		4/453 (0.9%)
Eye pain	2/452 (0.4%)		3/453 (0.7%)
Conjunctival haemorrhage	1/452 (0.2%)		2/453 (0.4%)
Conjunctival oedema	1/452 (0.2%)		0/453 (0%)
Eye discharge	1/452 (0.2%)		0/453 (0%)
Eyelid pruritus	1/452 (0.2%)		0/453 (0%)
Iritis	1/452 (0.2%)		0/453 (0%)
Ocular hypertension	1/452 (0.2%)		0/453 (0%)
Photophobia	1/452 (0.2%)		1/453 (0.2%)
Vision blurred	1/452 (0.2%)		6/453 (1.3%)
Vision acuity reduced	1/452 (0.2%)		0/453 (0%)
Visual impairment	1/452 (0.2%)		0/453 (0%)
Corneal infiltrates	0/452 (0%)		1/453 (0.2%)
Gastrointestinal disorders
Abdominal pain	1/452 (0.2%)		0/453 (0%)
Constipation	1/452 (0.2%)		0/453 (0%)
Gastroesophogeal reflux disease	1/452 (0.2%)		0/453 (0%)
Nausea	1/452 (0.2%)		1/453 (0.2%)
Oesophageal rupture	1/452 (0.2%)		0/453 (0%)
General disorders
Instillation site pain	26/452 (5.8%)		20/453 (4.4%)
Chest pain	1/452 (0.2%)		0/453 (0%)
Instillation site discharge	1/452 (0.2%)		0/453 (0%)
Instillation site irritation	1/452 (0.2%)		0/453 (0%)
Instillation site pruritus	0/452 (0%)		1/453 (0.2%)
Pyrexia	0/452 (0%)		1/453 (0.2%)
Immune system disorders
Drug hypersensitivity	1/452 (0.2%)		0/453 (0%)
Infections and infestations
Herpes zoster	1/452 (0.2%)		0/453 (0%)
Streptococcal infection	1/452 (0.2%)		0/453 (0%)
Tooth infection	1/452 (0.2%)		0/453 (0%)
Body tinea	0/452 (0%)		1/453 (0.2%)
Lower respiratory tract infection	0/452 (0%)		1/453 (0.2%)
Sinusitis	0/452 (0%)		1/453 (0.2%)
Upper respiratory tract infection	0/452 (0%)		2/453 (0.4%)
Vaginal infection	0/452 (0%)		1/453 (0.2%)
Injury, poisoning and procedural complications
Contusion	1/452 (0.2%)		0/453 (0%)
Joint injury	1/452 (0.2%)		1/453 (0.2%)
Ligament rupture	1/452 (0.2%)		0/453 (0%)
Investigations
Intraocular pressure increased	1/452 (0.2%)		0/453 (0%)
Musculoskeletal and connective tissue disorders
Osteoporosis	1/452 (0.2%)		0/453 (0%)
Nervous system disorders
Dizziness	1/452 (0.2%)		1/453 (0.2%)
Headache	1/452 (0.2%)		2/453 (0.4%)
Ophthalmoplegic migraine	0/452 (0%)		1/453 (0.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/452 (0.2%)		0/453 (0%)
Nasal congestion	1/452 (0.2%)		0/453 (0%)
Sinus congestion	1/452 (0.2%)		0/453 (0%)
Paranasal sinus hypersecretion	0/452 (0%)		1/453 (0.2%)
Skin and subcutaneous tissue disorders
Pruritus	0/452 (0%)		1/453 (0.2%)
Rash erythematous	0/452 (0%)		1/453 (0.2%)
Vascular disorders
Hypertension	1/452 (0.2%)		0/453 (0%)

Limitations/Caveats

[Not Specified]

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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.