VELOS-1: A Study to Assess Efficacy of HL036 in Subjects With Dry Eyes

• Sponsor: HanAll BioPharma Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03334539
• Collaborator: (none)
• Enrollment: 150
• Locations: 2
• Arms: 3
• Actual Duration (Months): 5.1
• Patients Per Site: 75
• Patients Per Site Per Month: 14.7

Study Details

Study Description

Brief Summary

The objective of this study was to compare the safety and efficacy of 0.10% and 0.25% HL036 Ophthalmic Solutions to placebo for the treatment of the signs and symptoms of dry eye.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye	Biological: HL036 ophthalmic solution; Other: Placebo vehicle solution	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Double-Masked and Placebo-Controlled Study Evaluating the Efficacy of Two Concentrations (0.10%, 0.25%) of HL036 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye
• Actual Study Start Date: Nov 5, 2017
• Actual Primary Completion Date: Apr 9, 2018
• Actual Study Completion Date: Apr 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.10% HL036 Ophthalmic Solution Participants self-administered HL036 0.10 percent (%) ophthalmic solution as topical ophthalmic drops, twice daily (BID) for up to 8 weeks. Exposures to the controlled adverse environment® (CAE) were conducted at Day 1, Day 15, Day 29 and Day 57.	Biological: HL036 ophthalmic solution; HL036 ophthalmic solution; Other Names: Tanfanercept
Experimental: 0.25% HL036 Ophthalmic Solution Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Biological: HL036 ophthalmic solution; HL036 ophthalmic solution; Other Names: Tanfanercept
Placebo Comparator: Placebo Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Other: Placebo vehicle solution; Placebo vehicle solution

Outcome Measures

Primary Outcome Measures

1. Coprimary Endpoint: Change From Baseline in Inferior Corneal Staining Score to Day 57 (Pre-CAE) [Baseline (Day 1 Pre-CAE), Day 57 (Pre-CAE)]

   It was evaluated for the inferior region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement.

2. Coprimary Endpoint: Change From Baseline in Ocular Discomfort Score to Day 57 (Pre-CAE) [Baseline (Day 1 Pre-CAE), Day 57 (Pre-CAE)]

   It is assessed by the Ora Calibra® Ocular Discomfort scale. The score ranged from 0 to 4 (0=none and 4=severe) with 1 point increments, where lower scores indicate improvement.

Secondary Outcome Measures

1. Mean Change From Baseline in Fluorescein Staining (Inferior Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

   It is evaluated for the inferior region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

2. Mean Change From Baseline in Fluorescein Staining (Superior Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

   It is evaluated for the superior region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

3. Mean Change From Baseline in Fluorescein Staining (Central Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

   It is evaluated for the central region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

4. Mean Change From Baseline in Fluorescein Staining (Temporal Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

   It is evaluated for the temporal region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

5. Mean Change From Baseline in Fluorescein Staining (Nasal Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

   It is evaluated for the nasal region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

6. Mean Change From Baseline in Fluorescein Staining (Corneal Sum) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

   Corneal sum score is the sum of all regions of the cornea (inferior, superior and central regions). Individual region score was evaluated on the Ora Calibra® and Conjunctival staining scale. Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Corneal sum score ranges from 0 to 12. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

7. Mean Change From Baseline in Fluorescein Staining (Conjunctival Sum) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

   Conjunctival sum score is the sum of all regions of the conjunctiva (temporal and nasal regions). Individual region score was evaluated on the Ora Calibra® and Conjunctival staining scale. Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Corneal sum score ranges from 0 to 8. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

8. Mean Change From Baseline in Fluorescein Staining Total Score (All Five Regions: Central, Superior, Inferior, Temporal, Nasal) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

   Total score was sum of all 5 regions: central, superior, inferior, temporal, and nasal. Individual region score was evaluated on the Ora Calibra® and Conjunctival staining scale. Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Total score ranges from 0 to 20. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

9. Mean Change From Baseline in Lissamine Green Staining Total Score (Inferior Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

   It is evaluated for the inferior region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

10. Mean Change From Baseline in Lissamine Green Staining Total Score (Superior Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    It is evaluated for the superior region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

11. Mean Change From Baseline in Lissamine Green Staining Total Score (Central Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    It is evaluated for the central region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

12. Mean Change From Baseline in Lissamine Green Staining Total Score (Temporal Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    It is evaluated for the temporal region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

13. Mean Change From Baseline in Lissamine Green Staining Total Score (Nasal Region) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    It is evaluated for the nasal region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

14. Mean Change From Baseline in Lissamine Green Staining Total Score (Corneal Sum) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Corneal sum score is the sum of all regions of the cornea (inferior, superior and central regions). Individual region score was evaluated on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Total score ranges from 0 to 12. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

15. Mean Change From Baseline in Lissamine Green Staining Total Score (Conjunctival Sum) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Conjunctival sum score is the sum of all regions of the conjunctiva (temporal and nasal regions). Individual region score was evaluated on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Total score ranges from 0 to 8. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

16. Mean Change From Baseline in Lissamine Green Staining Total Score (All Five Regions: Central, Superior, Inferior, Temporal, Nasal) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Total score was sum of all 5 regions: central, superior, inferior, temporal, and nasal. Individual region score was evaluated on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Total score ranges from 0 to 20. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.

17. Change From Baseline in Tear Film Break-Up Time [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Sodium fluorescein solution was instilled into each eye and participants were instructed to blinked several times. The time it takes to form micelles from the time that the eye is opened was noted.

18. Change From Baseline in the Ora Calibra® Conjunctival Redness Scale [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    It is evaluated by the Ora Calibra® conjunctival redness scale for dry eye. The score ranges from 0 to 4 (0=none and 4=severe), where lower score indicates improvement

19. Change From Baseline in Schirmer's Test [Baseline (Day 1); Days 15, 29, and 57]

    The Schirmer test strip will be placed in the lower temporal lid margin of each eye. Subjects will be instructed to close their eyes and After 5 minutes have elapsed, The length of moistened area of schirmer strip will be recorded (mm) for each eye.

20. Change From Baseline in Ora Calibra® Ocular Discomfort Scale [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    It was assessed by the Ora Calibra® ocular discomfort scale. The score ranges from 0 to 4 (0=none and 4=severe), where lower score indicates improvement.

21. Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Overall Ocular Discomfort) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of overall ocular discomfort at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.

22. Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Burning) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of burning at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.

23. Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Dryness) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of dryness at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.

24. Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Grittiness) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of grittiness at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.

25. Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Stinging) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of stinging at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.

26. Change From Baseline in Visual Analog Scale (Burning) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Participants rated ocular symptom of burning by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."

27. Change From Baseline in Visual Analog Scale (Itching) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Participants rated ocular symptom of itching by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."

28. Change From Baseline in Visual Analog Scale (Foreign Body) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Participants rated ocular symptom of foreign body by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."

29. Change From Baseline in Visual Analog Scale (Blurred Vision) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Participants rated ocular symptom of blurred vision by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."

30. Change From Baseline in Visual Analog Scale (Dryness) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Participants rated ocular symptom of dryness by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."

31. Change From Baseline in Visual Analog Scale (Photophobia) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Participants rated ocular symptom of photophobia by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."

32. Change From Baseline in Visual Analog Scale (Pain) [Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)]

    Participants rated ocular symptom of pain by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."

33. Change From Baseline in Ocular Surface and Disease Index (OSDI©) [Baseline (Day 1); Days 8, 15, 29, and 57]

    The OSDI is a simple 12-question survey that rates the severity of the participant's dry eye disease based on the symptoms. It is assessed on a scale of 0 to 100, with higher score representing greater disability.

34. Ora Calibra® Drop Comfort Scale [Upon instillation and 1 and 2 minutes post-instillation on Day 1]

    Ora Calibra® drop comfort scale ranges from 0 to 10. A score of 0 indicates comfortable and 10 indicates uncomfortable. Lower score indicated better comfort level.

35. Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Overall Ocular Discomfort) [From Baseline (Day 1) to Day 56]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of overall ocular discomfort twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.

36. Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Burning) [From Baseline (Day 1) to Day 56]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of burning twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.

37. Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Dryness) [From Baseline (Day 1) to Day 56]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of dryness twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.

38. Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Grittiness) [From Baseline (Day 1) to Day 56]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of grittiness twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.

39. Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Stinging) [From Baseline (Day 1) to Day 56]

    Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of stinging twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have a patient-reported history of dry eye for at least 6 months prior to enrollment

• Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1

• Have in the study eye a Schirmer's Test score of ≤ 10 mm and ≥ 1 mm at Visits 1 and 2

Exclusion Criteria:

• Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1

• Have used Restasis® or Xiidra® within 60 days of Visit 1

• Be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter (OTC) solutions, artificial tears, gels or scrubs, and cannot discontinue these medications for the duration of the trial (excluding medications allowed for the conduct of the study)

• Have an uncontrolled systemic disease

• Be a woman who is pregnant, nursing or planning a pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Maine Eye Care	Lewiston	Maine	United States	04240
2	Andover Eye Associates	Andover	Massachusetts	United States	01810

Sponsors and Collaborators

• HanAll BioPharma Co., Ltd.

Investigators

• Principal Investigator: Gail Torkildsen, MD, Andover Eye Associates

Study Documents (Full-Text)

• Study Protocol - Oct 31, 2017
• Statistical Analysis Plan - Mar 15, 2018

More Information

Publications

None provided.

• Responsible Party: HanAll BioPharma Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03334539
• Other Study ID Numbers: HL036-DED-US-P201
• First Posted: Nov 7, 2017
• Last Update Posted: Jan 26, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Pharmaceutical Solutions; Ophthalmic Solutions

Study Results

Participant Flow

Recruitment Details	Participants who met all the eligibility criteria were enrolled at 2 sites in the United States.
Pre-assignment Detail	All participants went through a placebo run-in period for 14 days prior to randomization. During the period, exposures to the controlled adverse environment® (CAE) were conducted to ascertain eligibility to enter the study. Those who qualified were randomized.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, twice daily (BID) for up to 8 weeks. Exposures to the controlled adverse environment (CAE®) were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Period Title: Overall Study
STARTED	50	50	50
COMPLETED	46	43	49
NOT COMPLETED	4	7	1

Baseline Characteristics

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo	Total
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Total of all reporting groups
Overall Participants	50	50	50	150
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.9 (13.09)	63.5 (9.92)	66.1 (11.38)	63.5 (11.65)
Sex: Female, Male (Count of Participants)
Female	30 60%	40 80%	38 76%	108 72%
Male	20 40%	10 20%	12 24%	42 28%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4%	1 2%	2 4%	5 3.3%
Not Hispanic or Latino	48 96%	49 98%	48 96%	145 96.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2%	0 0%	0 0%	1 0.7%
Asian	0 0%	1 2%	1 2%	2 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 2%	1 0.7%
White	49 98%	48 96%	48 96%	145 96.7%
More than one race	0 0%	1 2%	0 0%	1 0.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Coprimary Endpoint: Change From Baseline in Inferior Corneal Staining Score to Day 57 (Pre-CAE)
Description	It was evaluated for the inferior region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement.
Time Frame	Baseline (Day 1 Pre-CAE), Day 57 (Pre-CAE)

Outcome Measure Data

Analysis Population Description

ITT Population with the Markov Chain Monte Carlo (MCMC) imputation method for missing values.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo matching vehicle solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.94 (0.512)	1.96 (0.450)	1.95 (0.433)
Change From Baseline to Day 57 (pre-CAE)	0.10 (0.699)	0.10 (0.490)	-0.02 (0.631)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.10% HL036 Ophthalmic Solution, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3378
	Comments	P-value was calculated using a model with treatment, baseline score, and site as covariates.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.25% HL036 Ophthalmic Solution, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2883
	Comments	P-value was calculated using a model with treatment, baseline score, and site as covariates.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	0.10% HL036 Ophthalmic Solution, 0.25% HL036 Ophthalmic Solution
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9293
	Comments	P-value calculated using a model with treatment, baseline score, and site as covariates
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Coprimary Endpoint: Change From Baseline in Ocular Discomfort Score to Day 57 (Pre-CAE)
Description	It is assessed by the Ora Calibra® Ocular Discomfort scale. The score ranged from 0 to 4 (0=none and 4=severe) with 1 point increments, where lower scores indicate improvement.
Time Frame	Baseline (Day 1 Pre-CAE), Day 57 (Pre-CAE)

Outcome Measure Data

Analysis Population Description

ITT Population with the MCMC imputation method for missing values.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	2.6 (0.86)	2.5 (0.95)	2.4 (0.75)
Change from Baseline: Day 57 (Pre-CAE)	-0.5 (1.16)	-0.4 (1.33)	-0.1 (0.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.10% HL036 Ophthalmic Solution, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1473
	Comments	P-value calculated using a model with treatment, baseline score, and site as covariates.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.25% HL036 Ophthalmic Solution, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2321
	Comments	P-value calculated using a model with treatment, baseline score, and site as covariates.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	0.10% HL036 Ophthalmic Solution, 0.25% HL036 Ophthalmic Solution
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8217
	Comments	P-value calculated using a model with treatment, baseline score, and site as covariates.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Change From Baseline in Fluorescein Staining (Inferior Region)
Description	It is evaluated for the inferior region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.94 (0.512)	1.96 (0.450)	1.95 (0.443)
Day 1 Post-CAE	3.32 (0.492)	3.25 (0.565)	3.20 (0.474)
Day 1 (Change from Pre-CAE to Post-CAE)	1.38 (0.521)	1.29 (0.464)	1.25 (0.407)
Change from Baseline: Day 8	0.19 (0.706)	-0.01 (0.606)	0.04 (0.668)
Change from Baseline: Day 15 (Pre-CAE)	-0.12 (0.697)	-0.20 (0.608)	-0.10 (0.571)
Change from Baseline: Day 15 (Post-CAE)	-0.62 (0.766)	-0.85 (0.736)	-0.69 (0.826)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.50 (0.892)	-0.66 (0.793)	-0.59 (0.867)
Change from Baseline: Day 29 (Pre-CAE)	0.04 (0.807)	0.04 (0.563)	0.00 (0.707)
Change from Baseline: Day 29 (Post-CAE)	-0.41 (0.656)	-0.83 (0.677)	-0.48 (0.569)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.66 (0.857)	-1.02 (0.624)	-0.64 (0.591)
Change from Baseline: Day 57 (Pre-CAE)	0.12 (0.724)	0.10 (0.512)	-0.02 (0.631)
Change from Baseline: Day 57 (Post-CAE)	-0.47 (0.670)	-0.84 (0.738)	-0.63 (0.610)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.59 (0.878)	-0.92 (0.663)	-0.62 (0.747)

4. Secondary Outcome

Title	Mean Change From Baseline in Fluorescein Staining (Superior Region)
Description	It is evaluated for the superior region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	2.05 (0.420)	2.08 (0.444)	2.03 (0.456)
Day 1 Post-CAE	2.69 (0.552)	2.56 (0.559)	2.45 (0.556)
Day 1 (Change from Pre-CAE to Post-CAE)	0.64 (0.598)	0.48 (0.622)	0.42 (0.650)
Change from Baseline: Day 8	-0.09 (0.586)	-0.27 (0.592)	-0.09 (0.556)
Change from Baseline: Day 15 (Pre-CAE)	-0.22 (0.790)	-0.45 (0.724)	-0.29 (0.615)
Change from Baseline: Day 15 (Post-CAE)	-0.66 (0.976)	-0.72 (0.798)	-0.34 (0.658)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.44 (0.884)	-0.27 (0.743)	-0.05 (0.791)
Change from Baseline: Day 29 (Pre-CAE)	-0.27 (0.709)	-0.25 (0.555)	-0.10 (0.707)
Change from Baseline: Day 29 (Post-CAE)	-0.50 (0.655)	-0.65 (0.822)	-0.07 (0.604)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.41 (0.791)	-0.52 (0.964)	-0.09 (0.782)
Change from Baseline: Day 57 (Pre-CAE)	-0.09 (0.571)	-0.14 (0.594)	-0.19 (0.713)
Change from Baseline: Day 57 (Post-CAE)	-0.46 (0.665)	-0.37 (0.787)	-0.23 (0.662)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.37 (0.806)	-0.21 (0.847)	-0.08 (0.915)

5. Secondary Outcome

Title	Mean Change From Baseline in Fluorescein Staining (Central Region)
Description	It is evaluated for the central region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.45 (0.687)	1.57 (0.670)	1.49 (0.610)
Day 1 Post-CAE	2.22 (0.624)	2.09 (0.550)	2.04 (0.676)
Day 1 (Change from Pre-CAE to Post-CAE)	0.77 (0.641)	0.052 (0.735)	0.55 (0.633)
Change from Baseline: Day 8	0.12 (0.766)	-0.02 (0.887)	-0.05 (0.779)
Change from Baseline: Day 15 (Pre-CAE)	0.00 (0.869)	-0.24 (0.831)	-0.09 (0.780)
Change from Baseline: Day 15 (Post-CAE)	-0.52 (0.749)	-0.58 (0.732)	-0.42 (0.724)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.52 (0.963)	-0.34 (0.923)	-0.33 (0.956)
Change from Baseline: Day 29 (Pre-CAE)	0.01 (0.906)	-0.21 (0.771)	-0.07 (0.776)
Change from Baseline: Day 29 (Post-CAE)	-0.50 (0.612)	-0.54 (0.528)	-0.16 (0.653)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.69 (0.870)	-0.54 (0.948)	-0.20 (0.916)
Change from Baseline: Day 57 (Pre-CAE)	0.00 (0.837)	-0.10 (0.832)	-0.20 (0.802)
Change from Baseline: Day 57 (Post-CAE)	-0.36 (0.765)	-0.35 (0.856)	-0.30 (0.847)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.36 (1.089)	-0.23 (1.043)	-0.13 (0.846)

6. Secondary Outcome

Title	Mean Change From Baseline in Fluorescein Staining (Temporal Region)
Description	It is evaluated for the temporal region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	2.14 (0.452)	2.12 (0.521)	2.02 (0.622)
Day 1 Post-CAE	2.60 (0.606)	2.42 (0.538)	2.47 (0.519)
Day 1 (Change from Pre-CAE to Post-CAE)	0.46 (0.523)	0.30 (0.647)	0.45 (0.625)
Change from Baseline: Day 8	-0.01 (0.520)	-0.09 (0.598)	-0.13 (0.755)
Change from Baseline: Day 15 (Pre-CAE)	-0.34 (0.601)	-0.31 (0.741)	-0.14 (0.736)
Change from Baseline: Day 15 (Post-CAE)	-0.49 (0.739)	-0.54 (0.683)	-0.54 (0.552)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.15 (0.835)	-0.23 (0.765)	-0.40 (0.857)
Change from Baseline: Day 29 (Pre-CAE)	-0.19 (0.706)	-0.18 (0.828)	-0.10 (0.714)
Change from Baseline: Day 29 (Post-CAE)	-0.34 (0.569)	-0.38 (0.653)	-0.20 (0.478)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.26 (0.872)	-0.33 (0.894)	-0.20 (0.737)
Change from Baseline: Day 57 (Pre-CAE)	-0.07 (0.554)	0.06 (0.749)	-0.09 (0.754)
Change from Baseline: Day 57 (Post-CAE)	-0.30 (0.679)	-0.24 (0.767)	-0.33 (0.696)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.24 (0.842)	-0.28 (0.902)	-0.26 (0.824)

7. Secondary Outcome

Title	Mean Change From Baseline in Fluorescein Staining (Nasal Region)
Description	It is evaluated for the nasal region on the Ora Calibra® and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	2.27 (0.507)	2.26 (0.527)	2.14 (0.544)
Day 1 Post-CAE	2.74 (0.649)	2.67 (0.577)	2.68 (0.587)
Day 1 (Change from Pre-CAE to Post-CAE)	0.47 (0.557)	0.41 (0.541)	0.54 (0.638)
Change from Baseline: Day 8	-0.06 (0.501)	-0.05 (0.518)	-0.05 (0.702)
Change from Baseline: Day 15 (Pre-CAE)	-0.28 (0.743)	-0.29 (0.600)	-0.06 (0.620)
Change from Baseline: Day 15 (Post-CAE)	-0.44 (0.697)	-0.52 (0.785)	-0.51 (0.773)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.16 (0.830)	-0.23 (0.772)	-0.45 (0.859)
Change from Baseline: Day 29 (Pre-CAE)	-0.20 (0.735)	-0.18 (0.688)	-0.04 (0.783)
Change from Baseline: Day 29 (Post-CAE)	-0.17 (0.658)	-0.19 (0.694)	-0.20 (0.643)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.03 (0.755)	-0.06 (0.589)	-0.17 (0.877)
Change from Baseline: Day 57 (Pre-CAE)	-0.01 (0.771)	0.01 (0.678)	-0.24 (0.600)
Change from Baseline: Day 57 (Post-CAE)	-0.29 (0.671)	-0.26 (0.960)	-0.38 (0.718)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.28 (0.696)	-0.27 (0.928)	-0.15 (0.805)

8. Secondary Outcome

Title	Mean Change From Baseline in Fluorescein Staining (Corneal Sum)
Description	Corneal sum score is the sum of all regions of the cornea (inferior, superior and central regions). Individual region score was evaluated on the Ora Calibra® and Conjunctival staining scale. Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Corneal sum score ranges from 0 to 12. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	5.44 (1.232)	5.61 (1.230)	5.47 (1.154)
Day 1 Post-CAE	8.23 (1.318)	7.90 (1.241)	7.69 (1.340)
Day 1 (Change from Pre-CAE to Post-CAE)	2.79 (1.258)	2.29 (1.246)	2.22 (1.135)
Change from Baseline: Day 8	0.22 (1.559)	-0.30 (1.584)	-0.10 (1.544)
Change from Baseline: Day 15 (Pre-CAE)	-0.34 (1.939)	-0.89 (1.562)	-0.48 (1.474)
Change from Baseline: Day 15 (Post-CAE)	-1.80 (2.058)	-2.16 (1.695)	-1.45 (1.526)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-1.46 (1.935)	-1.27 (1.516)	-0.97 (1.739)
Change from Baseline: Day 29 (Pre-CAE)	-0.22 (1.995)	-0.42 (1.404)	-0.17 (1.704)
Change from Baseline: Day 29 (Post-CAE)	-1.41 (1.389)	-2.02 (1.360)	-0.71 (1.205)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-1.76 (1.850)	-2.08 (1.659)	-0.93 (1.438)
Change from Baseline: Day 57 (Pre-CAE)	0.03 (1.470)	-0.14 (1.579)	-0.41 (1.634)
Change from Baseline: Day 57 (Post-CAE)	-1.28 (1.618)	-1.56 (1.780)	-1.16 (1.748)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-1.32 (2.034)	-1.36 (1.881)	-0.84 (1.801)

9. Secondary Outcome

Title	Mean Change From Baseline in Fluorescein Staining (Conjunctival Sum)
Description	Conjunctival sum score is the sum of all regions of the conjunctiva (temporal and nasal regions). Individual region score was evaluated on the Ora Calibra® and Conjunctival staining scale. Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Corneal sum score ranges from 0 to 8. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	4.41 (0.879)	4.38 (0.923)	4.16 (1.052)
Day 1 Post-CAE	5.34 (1.118)	5.09 (0.941)	5.15 (0.981)
Day 1 (Change from Pre-CAE to Post-CAE)	0.93 (0.827)	0.71 (0.964)	0.99 (1.095)
Change from Baseline: Day 8	-0.07 (0.845)	-0.15 (0.875)	-0.18 (1.349)
Change from Baseline: Day 15 (Pre-CAE)	-0.62 (1.167)	-0.60 (1.158)	-0.20 (1.143)
Change from Baseline: Day 15 (Post-CAE)	-0.93 (1.212)	-1.06 (1.295)	-1.05 (1.135)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.31 (1.269)	-0.46 (1.258)	-0.85 (1.440)
Change from Baseline: Day 29 (Pre-CAE)	-0.39 (1.263)	-0.35 (1.360)	-0.14 (1.327)
Change from Baseline: Day 29 (Post-CAE)	-0.52 (0.986)	-0.58 (1.206)	-0.39 (0.927)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.29 (1.379)	-0.38 (1.219)	-0.37 (1.377)
Change from Baseline: Day 57 (Pre-CAE)	-0.08 (1.178)	0.07 (1.269)	-0.33 (1.223)
Change from Baseline: Day 57 (Post-CAE)	-0.60 (1.177)	-0.50 (1.528)	-0.70 (1.194)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.52 (1.273)	-0.55 (1.573)	-0.41 (1.306)

10. Secondary Outcome

Title	Mean Change From Baseline in Fluorescein Staining Total Score (All Five Regions: Central, Superior, Inferior, Temporal, Nasal)
Description	Total score was sum of all 5 regions: central, superior, inferior, temporal, and nasal. Individual region score was evaluated on the Ora Calibra® and Conjunctival staining scale. Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Total score ranges from 0 to 20. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	9.85 (1.852)	9.99 (1.777)	9.63 (1.982)
Day 1 Post-CAE	13.57 (2.143)	12.99 (1.828)	12.84 (1.872)
Day 1 (Change from Pre-CAE to Post-CAE)	3.72 (1.614)	3.00 (1.684)	3.21 (1.890)
Change from Baseline: Day 8	0.15 (2.139)	-0.45 (2.009)	-0.29 (2.667)
Change from Baseline: Day 15 (Pre-CAE)	-0.96 (2.866)	-1.49 (2.312)	-0.68 (2.338)
Change from Baseline: Day 15 (Post-CAE)	-2.73 (2.875)	-3.22 (2.664)	-2.50 (2.150)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-1.77 (2.686)	-1.73 (2.245)	-1.82 (2.676)
Change from Baseline: Day 29 (Pre-CAE)	-0.61 (2.933)	-0.77 (2.214)	-0.30 (2.710)
Change from Baseline: Day 29 (Post-CAE)	-1.93 (1.831)	-2.60 (2.168)	-1.11 (1.739)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-2.05 (2.530)	-2.46 (2.054)	-1.30 (2.403)
Change from Baseline: Day 57 (Pre-CAE)	-0.04 (2.250)	-0.07 (2.403)	-0.74 (2.560)
Change from Baseline: Day 57 (Post-CAE)	-1.88 (2.400)	-2.06 (2.990)	-1.87 (2.559)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-1.84 (2.763)	-1.91 (2.922)	-1.24 (2.387)

11. Secondary Outcome

Title	Mean Change From Baseline in Lissamine Green Staining Total Score (Inferior Region)
Description	It is evaluated for the inferior region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.42 (0.642)	1.46 (0.605)	1.50 (0.580)
Day 1 Post-CAE	2.00 (0.920)	2.12 (0.895)	1.87 (0.826)
Day 1 (Change from Pre-CAE to Post-CAE)	0.58 (0.752)	0.66 (0.934)	0.37 (0.850)
Change from Baseline: Day 8	0.04 (0.699)	-0.30 (0.642)	-0.08 (0.702)
Change from Baseline: Day 15 (Pre-CAE)	-0.34 (0.805)	-0.43 (0.644)	-0.48 (0.707)
Change from Baseline: Day 15 (Post-CAE)	-0.46 (1.228)	-0.76 (0.984)	-0.34 (1.104)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.12 (0.982)	-0.33 (0.919)	0.14 (1.170)
Change from Baseline: Day 29 (Pre-CAE)	-0.14 (0.815)	-0.24 (0.715)	-0.28 (0.607)
Change from Baseline: Day 29 (Post-CAE)	-0.10 (1.191)	-0.69 (0.895)	-0.20 (1.074)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.10 (1.064)	-0.60 (0.949)	0.16 (1.147)
Change from Baseline: Day 57 (Pre-CAE)	-0.21 (0.637)	-0.17 (0.869)	-0.34 (0.688)
Change from Baseline: Day 57 (Post-CAE)	-0.16 (0.943)	-0.60 (0.877)	-0.22 (0.764)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.04 (0.881)	-0.38 (1.179)	0.07 (0.866)

12. Secondary Outcome

Title	Mean Change From Baseline in Lissamine Green Staining Total Score (Superior Region)
Description	It is evaluated for the superior region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.22 (0.507)	1.32 (0.560)	1.27 (0.546)
Day 1 Post-CAE	1.48 (0.580)	1.51 (0.703)	1.44 (0.697)
Day 1 (Change from Pre-CAE to Post-CAE)	0.26 (0.527)	0.19 (0.669)	0.17 (0.760)
Change from Baseline: Day 8	-0.14 (0.525)	-0.31 (0.624)	-0.18 (0.537)
Change from Baseline: Day 15 (Pre-CAE)	-0.37 (0.838)	-0.57 (0.772)	-0.38 (0.907)
Change from Baseline: Day 15 (Post-CAE)	-0.48 (0.931)	-0.66 (0.870)	-0.34 (0.866)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.11 (0.841)	-0.08 (0.808)	0.04 (0.936)
Change from Baseline: Day 29 (Pre-CAE)	-0.29 (0.729)	-0.33 (0.604)	-0.44 (0.712)
Change from Baseline: Day 29 (Post-CAE)	-0.19 (0.806)	-0.31 (0.849)	0.02 (0.713)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.14 (0.789)	-0.04 (0.916)	0.30 (0.896)
Change from Baseline: Day 57 (Pre-CAE)	-0.32 (0.541)	-0.36 (0.694)	-0.40 (0.769)
Change from Baseline: Day 57 (Post-CAE)	-0.37 (0.679)	-0.44 (0.717)	-0.28 (0.736)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.05 (0.797)	-0.05 (0.762)	0.08 (0.915)

13. Secondary Outcome

Title	Mean Change From Baseline in Lissamine Green Staining Total Score (Central Region)
Description	It is evaluated for the central region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	0.48 (0.735)	0.57 (0.742)	0.54 (0.734)
Day 1 Post-CAE	0.59 (0.780)	0.60 (0.735)	0.66 (0.823)
Day 1 (Change from Pre-CAE to Post-CAE)	0.11 (0.547)	0.03 (0.519)	0.12 (0.799)
Change from Baseline: Day 8	-0.13 (0.676)	-0.29 (0.582)	-0.24 (0.723)
Change from Baseline: Day 15 (Pre-CAE)	-0.13 (0.720)	-0.26 (0.636)	-0.24 (0.744)
Change from Baseline: Day 15 (Post-CAE)	-0.33 (0.636)	-0.29 (0.706)	-0.30 (0.647)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.20 (0.776)	-0.03 (0.815)	-0.06 (0.935)
Change from Baseline: Day 29 (Pre-CAE)	-0.31 (0.630)	-0.22 (0.837)	-0.28 (0.730)
Change from Baseline: Day 29 (Post-CAE)	-0.07 (0.258)	-0.15 (0.660)	-0.07 (0.466)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	0.03 (0.680)	-0.17 (0.677)	0.11 (0.956)
Change from Baseline: Day 57 (Pre-CAE)	-0.23 (0.555)	-0.31 (0.667)	-0.16 (0.681)
Change from Baseline: Day 57 (Post-CAE)	-0.14 (0.602)	-0.34 (0.898)	-0.31 (0.619)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.09 (0.652)	-0.02 (0.879)	-0.18 (0.782)

14. Secondary Outcome

Title	Mean Change From Baseline in Lissamine Green Staining Total Score (Temporal Region)
Description	It is evaluated for the temporal region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.63 (0.706)	1.63 (0.669)	1.61 (0.751)
Day 1 Post-CAE	1.87 (0.691)	1.71 (0.671)	1.87 (0.734)
Day 1 (Change from Pre-CAE to Post-CAE)	0.24 (0.649)	0.08 (0.695)	0.26 (0.834)
Change from Baseline: Day 8	-0.09 (0.733)	-0.11 (0.864)	-0.15 (0.686)
Change from Baseline: Day 15 (Pre-CAE)	-0.32 (0.885)	-0.48 (0.707)	-0.46 (0.885)
Change from Baseline: Day 15 (Post-CAE)	-0.37 (0.669)	-0.50 (0.772)	-0.50 (0.606)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.05 (0.876)	-0.02 (0.928)	-0.04 (0.919)
Change from Baseline: Day 29 (Pre-CAE)	-0.29 (0.915)	-0.21 (0.683)	-0.19 (0.630)
Change from Baseline: Day 29 (Post-CAE)	-0.28 (0.663)	-0.06 (0.668)	-0.25 (0.569)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.09 (1.142)	0.08 (0.688)	-0.05 (0.916)
Change from Baseline: Day 57 (Pre-CAE)	-0.26 (0.721)	-0.20 (0.816)	-0.16 (0.710)
Change from Baseline: Day 57 (Post-CAE)	-0.21 (0.750)	-0.22 (0.934)	-0.22 (0.715)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.05 (1.029)	0.03 (0.947)	-0.07 (1.066)

15. Secondary Outcome

Title	Mean Change From Baseline in Lissamine Green Staining Total Score (Nasal Region)
Description	It is evaluated for the nasal region on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.90 (0.707)	1.96 (0.561)	1.69 (0.638)
Day 1 Post-CAE	2.18 (0.774)	2.05 (0.828)	1.93 (0.693)
Day 1 (Change from Pre-CAE to Post-CAE)	0.28 (0.640)	0.09 (0.740)	0.24 (0.816)
Change from Baseline: Day 8	-0.04 (0.748)	-0.25 (0.668)	0.00 (0.677)
Change from Baseline: Day 15 (Pre-CAE)	-0.22 (0.723)	-0.48 (0.660)	-0.23 (0.822)
Change from Baseline: Day 15 (Post-CAE)	-0.23 (0.858)	-0.29 (0.904)	-0.24 (0.672)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.01 (0.901)	0.19 (1.070)	-0.01 (1.013)
Change from Baseline: Day 29 (Pre-CAE)	-0.28 (0.679)	-0.39 (0.638)	-0.03 (0.785)
Change from Baseline: Day 29 (Post-CAE)	-0.19 (0.737)	0.10 (0.749)	-0.11 (0.854)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	0.09 (0.780)	0.52 (0.781)	-0.02 (1.004)
Change from Baseline: Day 57 (Pre-CAE)	-0.12 (0.709)	-0.31 (0.692)	-0.10 (0.721)
Change from Baseline: Day 57 (Post-CAE)	-0.26 (0.815)	-0.16 (0.843)	-0.02 (0.841)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.14 (0.821)	0.17 (0.872)	0.05 (0.959)

16. Secondary Outcome

Title	Mean Change From Baseline in Lissamine Green Staining Total Score (Corneal Sum)
Description	Corneal sum score is the sum of all regions of the cornea (inferior, superior and central regions). Individual region score was evaluated on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Total score ranges from 0 to 12. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	3.12 (1.272)	3.35 (1.360)	3.31 (1.344)
Day 1 Post-CAE	4.07 (1.705)	4.23 (1.785)	3.97 (1.828)
Day 1 (Change from Pre-CAE to Post-CAE)	0.95 (1.314)	0.88 (1.683)	0.66 (1.701)
Change from Baseline: Day 8	-0.23 (1.258)	-0.91 (1.382)	-0.51 (1.375)
Change from Baseline: Day 15 (Pre-CAE)	-0.84 (1.633)	-1.26 (1.568)	-1.10 (1.909)
Change from Baseline: Day 15 (Post-CAE)	-1.27 (2.264)	-1.71 (2.118)	-0.98 (1.924)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.43 (1.648)	-0.45 (1.952)	0.12 (1.965)
Change from Baseline: Day 29 (Pre-CAE)	-0.74 (1.516)	-0.79 (1.487)	-1.00 (1.488)
Change from Baseline: Day 29 (Post-CAE)	-0.36 (1.782)	-1.15 (1.754)	-0.25 (1.430)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.21 (1.578)	-0.81 (1.588)	0.57 (1.783)
Change from Baseline: Day 57 (Pre-CAE)	-0.75 (1.228)	-0.84 (1.751)	-0.90 (1.793)
Change from Baseline: Day 57 (Post-CAE)	-0.67 (1.674)	-1.38 (1.936)	-0.81 (1.439)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.08 (1.494)	-0.45 (2.154)	-0.03 (1.586)

17. Secondary Outcome

Title	Mean Change From Baseline in Lissamine Green Staining Total Score (Conjunctival Sum)
Description	Conjunctival sum score is the sum of all regions of the conjunctiva (temporal and nasal regions). Individual region score was evaluated on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Total score ranges from 0 to 8. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	3.53 (1.231)	3.59 (1.058)	3.30 (1.237)
Day 1 Post-CAE	4.05 (1.314)	3.76 (1.322)	3.80 (1.262)
Day 1 (Change from Pre-CAE to Post-CAE)	0.52 (1.092)	0.17 (1.223)	0.50 (1.403)
Change from Baseline: Day 8	-0.13 (1.249)	-0.36 (1.197)	-0.15 (1.133)
Change from Baseline: Day 15 (Pre-CAE)	-0.54 (1.417)	-0.96 (1.056)	-0.69 (1.548)
Change from Baseline: Day 15 (Post-CAE)	-0.60 (1.245)	-0.79 (1.228)	-0.74 (1.084)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.06 (1.427)	0.17 (1.524)	-0.05 (1.724)
Change from Baseline: Day 29 (Pre-CAE)	-0.57 (1.336)	-0.59 (1.090)	-0.22 (1.112)
Change from Baseline: Day 29 (Post-CAE)	-0.47 (1.195)	0.04 (1.264)	-0.36 (1.154)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	0.00 (1.553)	0.60 (1.200)	-0.07 (1.412)
Change from Baseline: Day 57 (Pre-CAE)	-0.38 (1.175)	-0.51 (1.349)	-0.26 (1.222)
Change from Baseline: Day 57 (Post-CAE)	-0.47 (1.356)	-0.38 (1.577)	-0.24 (1.377)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.09 (1.668)	0.21 (1.461)	-0.02 (1.723)

18. Secondary Outcome

Title	Mean Change From Baseline in Lissamine Green Staining Total Score (All Five Regions: Central, Superior, Inferior, Temporal, Nasal)
Description	Total score was sum of all 5 regions: central, superior, inferior, temporal, and nasal. Individual region score was evaluated on the lissamine green corneal and conjunctival staining scale (Ora Calibra® scale). Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Total score ranges from 0 to 20. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	6.65 (2.277)	6.94 (2.091)	6.61 (2.223)
Day 1 Post-CAE	8.12 (2.653)	7.99 (2.753)	7.77 (2.741)
Day 1 (Change from Pre-CAE to Post-CAE)	1.47 (1.923)	1.05 (2.493)	1.16 (2.708)
Change from Baseline: Day 8	-0.36 (2.124)	-1.27 (2.065)	-0.66 (2.090)
Change from Baseline: Day 15 (Pre-CAE)	-1.38 (2.767)	-2.22 (2.193)	-1.79 (3.059)
Change from Baseline: Day 15 (Post-CAE)	-1.87 (3.156)	-2.50 (2.836)	-1.72 (2.607)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.49 (2.409)	-0.28 (2.633)	0.07 (3.161)
Change from Baseline: Day 29 (Pre-CAE)	-1.31 (2.435)	-1.39 (2.038)	-1.22 (2.150)
Change from Baseline: Day 29 (Post-CAE)	-0.83 (2.369)	-1.12 (2.455)	-0.61 (2.025)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.21 (2.551)	-0.21 (2.016)	0.50 (2.553)
Change from Baseline: Day 57 (Pre-CAE)	-1.13 (1.815)	-1.35 (2.684)	-1.16 (2.616)
Change from Baseline: Day 57 (Post-CAE)	-1.14 (2.635)	-1.77 (3.087)	-1.05 (2.424)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.01 (2.568)	-0.24 (3.138)	-0.05 (2.716)

19. Secondary Outcome

Title	Change From Baseline in Tear Film Break-Up Time
Description	Sodium fluorescein solution was instilled into each eye and participants were instructed to blinked several times. The time it takes to form micelles from the time that the eye is opened was noted.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.559 (0.5031)	1.709 (0.7083)	1.574 (0.5394)
Day 1 Post-CAE	1.533 (0.5217)	1.555 (0.5441)	1.574 (0.5322)
Day 1 (Change from Pre-CAE to Post-CAE)	-0.027 (0.4552)	-0.154 (0.5516)	-0.001 (0.3670)
Change from Baseline: Day 8	0.024 (0.4943)	-0.037 (0.7421)	-0.036 (0.4948)
Change from Baseline: Day 15 (Pre-CAE)	0.386 (0.8008)	0.127 (0.7945)	0.276 (0.7857)
Change from Baseline: Day 15 (Post-CAE)	0.312 (0.9470)	0.195 (0.6835)	0.222 (0.7884)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.075 (0.7355)	0.068 (0.6543)	-0.054 (0.6252)
Change from Baseline: Day 29 (Pre-CAE)	0.218 (0.7586)	-0.191 (0.5936)	-0.077 (0.5228)
Change from Baseline: Day 29 (Post-CAE)	0.123 (0.7116)	0.086 (0.6752)	-0.188 (0.3884)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.054 (0.5013)	0.129 (0.4258)	-0.119 (0.5623)
Change from Baseline: Day 57 (Pre-CAE)	0.139 (0.5727)	-0.036 (0.8880)	0.186 (0.6696)
Change from Baseline: Day 57 (Post-CAE)	0.118 (0.7072)	0.039 (0.6057)	0.160 (0.7206)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.021 (0.6113)	0.063 (0.8557)	-0.003 (0.6473)

20. Secondary Outcome

Title	Change From Baseline in the Ora Calibra® Conjunctival Redness Scale
Description	It is evaluated by the Ora Calibra® conjunctival redness scale for dry eye. The score ranges from 0 to 4 (0=none and 4=severe), where lower score indicates improvement
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.70 (0.639)	1.66 (0.566)	1.72 (0.536)
Day 1 Post-CAE	2.03 (0.626)	2.02 (0.571)	2.04 (0.523)
Day 1 (Change from Pre-CAE to Post-CAE)	0.33 (0.603)	0.36 (0.655)	0.32 (0.569)
Change from Baseline: Day 8	0.04 (0.588)	-0.07 (0.473)	0.00 (0.669)
Change from Baseline: Day 15 (Pre-CAE)	-0.20 (0.606)	-0.17 (0.559)	-0.17 (0.568)
Change from Baseline: Day 15 (Post-CAE)	-0.14 (0.663)	-0.35 (0.515)	-0.20 (0.606)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	0.06 (0.983)	-0.19 (0.836)	-0.03 (0.785)
Change from Baseline: Day 29 (Pre-CAE)	-0.06 (0.740)	-0.03 (0.614)	-0.10 (0.685)
Change from Baseline: Day 29 (Post-CAE)	-0.22 (0.635)	-0.31 (0.601)	-0.21 (0.568)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.05 (0.967)	-0.21 (0.907)	-0.11 (1.012)
Change from Baseline: Day 57 (Pre-CAE)	0.01 (0.563)	0.23 (0.660)	0.11 (0.565)
Change from Baseline: Day 57 (Post-CAE)	-0.03 (0.591)	-0.01 (0.728)	-0.14 (0.586)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.04 (0.788)	-0.22 (0.941)	-0.28 (0.708)

21. Secondary Outcome

Title	Change From Baseline in Schirmer's Test
Description	The Schirmer test strip will be placed in the lower temporal lid margin of each eye. Subjects will be instructed to close their eyes and After 5 minutes have elapsed, The length of moistened area of schirmer strip will be recorded (mm) for each eye.
Time Frame	Baseline (Day 1); Days 15, 29, and 57

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 percent (%) ophthalmic solution as topical ophthalmic drops, twice daily (BID) for up to 8 weeks. Exposures to the controlled adverse environment® (CAE) were conducted at Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the controlled adverse environment® (CAE) were conducted at Day 15, Day 29 and Day 57.	Participants sefl-administered HL036 placebo matching vehicle solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the controlled adverse environment® (CAE) were conducted at Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1	5.0 (2.60)	5.2 (3.03)	5.5 (3.02)
Change From Baseline: Day 15	1.7 (5.21)	4.0 (7.36)	3.4 (6.50)
Change From Baseline: Day 29	0.8 (5.01)	0.9 (4.23)	1.8 (4.35)
Change From Baseline: Day 57	3.5 (6.70)	2.9 (4.74)	3.3 (6.84)

22. Secondary Outcome

Title	Change From Baseline in Ora Calibra® Ocular Discomfort Scale
Description	It was assessed by the Ora Calibra® ocular discomfort scale. The score ranges from 0 to 4 (0=none and 4=severe), where lower score indicates improvement.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	2.6 (0.86)	2.5 (0.95)	2.4 (0.75)
Day 1 Post-CAE	3.8 (0.52)	3.7 (0.47)	3.8 (0.52)
Day 1 (Change from Pre-CAE to Post-CAE)	1.2 (0.98)	1.2 (1.01)	1.4 (0.81)
Change from Baseline: Day 8	-0.5 (0.89)	0.1 (0.81)	-0.1 (1.01)
Change from Baseline: Day 15 (Pre-CAE)	-0.5 (0.71)	-0.1 (0.96)	-0.1 (0.87)
Change from Baseline: Day 15 (Post-CAE)	0.0 (0.62)	0.0 (0.58)	0.0 (0.55)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	0.5 (0.91)	0.1 (1.13)	0.1 (1.05)
Change from Baseline: Day 29 (Pre-CAE)	-0.4 (1.03)	-0.3 (0.92)	-0.2 (1.05)
Change from Baseline: Day 29 (Post-CAE)	0.0 (0.63)	-0.2 (0.63)	0.0 (0.88)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	0.5 (1.18)	0.0 (1.11)	0.1 (1.36)
Change from Baseline: Day 57 (Pre-CAE)	-0.5 (1.17)	-0.4 (1.39)	-0.1 (0.88)
Change from Baseline: Day 57 (Post-CAE)	-0.2 (0.77)	-0.1 (0.65)	-0.2 (0.76)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.3 (1.30)	0.4 (1.43)	-0.1 (1.17)

23. Secondary Outcome

Title	Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Overall Ocular Discomfort)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of overall ocular discomfort at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	2.9 (0.88)	2.7 (1.09)	2.8 (0.78)
Day 1 Post-CAE	3.8 (0.57)	3.7 (0.81)	4.0 (0.74)
Day 1 (Change from Pre-CAE to Post-CAE)	0.9 (0.82)	1.0 (1.11)	1.2 (0.92)
Change from Baseline: Day 8	-0.3 (0.97)	0.0 (0.98)	-0.2 (0.90)
Change from Baseline: Day 15 (Pre-CAE)	-0.4 (0.93)	0.0 (1.00)	-0.1 (0.97)
Change from Baseline: Day 15 (Post-CAE)	-0.2 (0.78)	0.0 (0.66)	-0.2 (0.95)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	0.2 (1.13)	0.0 (1.07)	0.0 (1.40)
Change from Baseline: Day 29 (Pre-CAE)	-0.3 (1.05)	-0.3 (1.19)	-0.3 (1.17)
Change from Baseline: Day 29 (Post-CAE)	-0.1 (0.90)	0.0 (0.89)	-0.1 (0.72)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	0.3 (1.03)	0.3 (1.23)	0.2 (1.49)
Change from Baseline: Day 57 (Pre-CAE)	-0.5 (1.35)	-0.4 (1.35)	-0.2 (1.06)
Change from Baseline: Day 57 (Post-CAE)	-0.2 (0.86)	0.0 (0.64)	-0.4 (0.98)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.3 (1.47)	0.5 (1.32)	-0.1 (1.33)

24. Secondary Outcome

Title	Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Burning)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of burning at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.6 (1.31)	1.4 (1.35)	1.2 (1.28)
Day 1 Post-CAE	2.5 (1.49)	2.3 (1.55)	2.4 (1.66)
Day 1 (Change from Pre-CAE to Post-CAE)	1.0 (1.26)	0.9 (1.12)	1.2 (1.29)
Change from Baseline: Day 8	-0.1 (0.81)	0.0 (0.92)	0.0 (0.85)
Change from Baseline: Day 15 (Pre-CAE)	-0.1 (1.04)	-0.2 (1.14)	0.0 (0.74)
Change from Baseline: Day 15 (Post-CAE)	-0.1 (1.16)	0.0 (1.17)	-0.1 (1.05)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	0.0 (1.62)	0.2 (1.40)	-0.1 (1.40)
Change from Baseline: Day 29 (Pre-CAE)	-0.1 (1.14)	-0.2 (1.18)	0.0 (0.84)
Change from Baseline: Day 29 (Post-CAE)	-0.1 (1.35)	-0.2 (0.97)	-0.1 (0.85)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	0.1 (1.25)	0.4 (1.24)	-0.3 (1.21)
Change from Baseline: Day 57 (Pre-CAE)	-0.1 (1.22)	-0.5 (1.50)	-0.1 (0.93)
Change from Baseline: Day 57 (Post-CAE)	-0.2 (1.09)	-0.1 (1.28)	-0.3 (1.01)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.1 (1.48)	0.5 (1.26)	-0.2 (1.30)

25. Secondary Outcome

Title	Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Dryness)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of dryness at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	3.1 (0.87)	3.1 (1.03)	3.0 (0.84)
Day 1 Post-CAE	4.0 (0.71)	3.9 (0.80)	4.1 (0.63)
Day 1 (Change from Pre-CAE to Post-CAE)	1.0 (0.86)	0.9 (0.76)	1.1 (0.99)
Change from Baseline: Day 8	-0.4 (0.90)	-0.1 (0.70)	-0.2 (0.77)
Change from Baseline: Day 15 (Pre-CAE)	-0.3 (0.80)	-0.2 (0.90)	-0.1 (0.76)
Change from Baseline: Day 15 (Post-CAE)	-0.2 (0.71)	-0.2 (0.80)	-0.1 (0.95)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	0.1 (1.08)	0.0 (0.98)	0.0 (1.29)
Change from Baseline: Day 29 (Pre-CAE)	-0.2 (1.03)	-0.4 (1.01)	-0.3 (0.94)
Change from Baseline: Day 29 (Post-CAE)	-0.3 (1.04)	-0.2 (0.67)	-0.2 (0.79)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	0.0 (0.98)	0.5 (1.17)	0.1 (1.33)
Change from Baseline: Day 57 (Pre-CAE)	-0.4 (1.25)	-0.3 (1.20)	-0.2 (1.08)
Change from Baseline: Day 57 (Post-CAE)	-0.2 (0.85)	-0.1 (0.82)	-0.3 (1.09)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.1 (1.31)	0.3 (1.04)	-0.1 (1.36)

26. Secondary Outcome

Title	Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Grittiness)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of grittiness at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	2.1 (1.27)	1.8 (1.47)	2.0 (1.35)
Day 1 Post-CAE	2.7 (1.40)	2.3 (1.63)	3.0 (1.28)
Day 1 (Change from Pre-CAE to Post-CAE)	0.7 (1.10)	0.5 (0.96)	1.1 (1.10)
Change from Baseline: Day 8	-0.2 (1.06)	-0.1 (0.67)	0.1 (0.95)
Change from Baseline: Day 15 (Pre-CAE)	-0.1 (1.05)	0.2 (1.06)	0.0 (0.68)
Change from Baseline: Day 15 (Post-CAE)	-0.1 (1.00)	0.2 (1.24)	-0.3 (1.07)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	0.0 (1.29)	0.0 (1.03)	-0.3 (1.33)
Change from Baseline: Day 29 (Pre-CAE)	-0.2 (1.25)	-0.1 (1.18)	-0.2 (1.04)
Change from Baseline: Day 29 (Post-CAE)	-0.2 (0.99)	0.1 (1.03)	-0.1 (0.74)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	0.1 (1.18)	0.3 (1.01)	0.0 (1.22)
Change from Baseline: Day 57 (Pre-CAE)	-0.4 (1.20)	-0.1 (1.29)	-0.1 (0.94)
Change from Baseline: Day 57 (Post-CAE)	-0.3 (1.06)	0.2 (1.13)	-0.6 (1.08)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.0 (1.44)	0.3 (1.09)	-0.4 (1.14)

27. Secondary Outcome

Title	Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Stinging)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of stinging at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity.
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	1.5 (1.33)	1.2 (1.35)	1.0 (1.08)
Day 1 Post-CAE	2.3 (1.42)	1.9 (1.55)	2.0 (1.67)
Day 1 (Change from Pre-CAE to Post-CAE)	0.8 (1.18)	0.7 (1.05)	1.0 (1.26)
Change from Baseline: Day 8	-0.3 (0.92)	-0.2 (0.86)	-0.1 (0.69)
Change from Baseline: Day 15 (Pre-CAE)	-0.2 (1.04)	-0.2 (1.08)	0.0 (0.76)
Change from Baseline: Day 15 (Post-CAE)	-0.3 (1.12)	0.0 (1.00)	-0.1 (1.19)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	0.0 (1.34)	0.2 (1.24)	-0.1 (1.41)
Change from Baseline: Day 29 (Pre-CAE)	-0.2 (1.12)	-0.3 (1.03)	-0.1 (0.90)
Change from Baseline: Day 29 (Post-CAE)	-0.3 (1.23)	-0.4 (1.06)	-0.2 (1.28)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	0.0 (1.16)	0.1 (1.06)	-0.2 (1.47)
Change from Baseline: Day 57 (Pre-CAE)	-0.2 (1.35)	-0.3 (1.40)	-0.1 (1.01)
Change from Baseline: Day 57 (Post-CAE)	-0.3 (1.12)	-0.1 (1.28)	-0.4 (1.30)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.0 (1.83)	0.3 (1.41)	-0.3 (1.51)

28. Secondary Outcome

Title	Change From Baseline in Visual Analog Scale (Burning)
Description	Participants rated ocular symptom of burning by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	30.4 (28.53)	29.3 (26.74)	22.4 (24.60)
Day 1 Post-CAE	44.6 (29.99)	44.1 (33.91)	40.1 (32.15)
Day 1 (Change from Pre-CAE to Post-CAE)	14.2 (23.57)	14.5 (22.27)	17.7 (22.75)
Change from Baseline: Day 8	-1.9 (19.34)	-4.5 (25.73)	0.5 (16.66)
Change from Baseline: Day 15 (Pre-CAE)	-3.0 (19.75)	-6.7 (24.08)	0.3 (11.84)
Change from Baseline: Day 15 (Post-CAE)	-1.6 (23.56)	-10.8 (24.27)	-2.2 (16.90)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	1.4 (26.91)	-3.5 (21.46)	-2.6 (17.42)
Change from Baseline: Day 29 (Pre-CAE)	-3.0 (26.13)	-6.6 (26.82)	-0.4 (15.67)
Change from Baseline: Day 29 (Post-CAE)	-7.3 (21.43)	-8.8 (26.93)	-3.2 (16.00)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-0.2 (23.76)	2.4 (25.72)	-4.0 (24.77)
Change from Baseline: Day 57 (Pre-CAE)	-3.5 (27.19)	-10.0 (31.76)	-1.5 (16.19)
Change from Baseline: Day 57 (Post-CAE)	-1.3 (20.26)	-10.3 (26.98)	-4.6 (21.47)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	2.2 (33.08)	2.2 (30.19)	-3.0 (23.35)

29. Secondary Outcome

Title	Change From Baseline in Visual Analog Scale (Itching)
Description	Participants rated ocular symptom of itching by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	28.6 (27.09)	26.2 (29.26)	26.8 (23.70)
Day 1 Post-CAE	37.0 (30.45)	31.9 (33.26)	35.0 (28.92)
Day 1 (Change from Pre-CAE to Post-CAE)	8.4 (21.67)	5.2 (18.00)	8.2 (22.76)
Change from Baseline: Day 8	-6.0 (19.05)	-2.8 (22.23)	0.5 (19.54)
Change from Baseline: Day 15 (Pre-CAE)	-3.1 (19.18)	-4.5 (18.28)	1.6 (20.27)
Change from Baseline: Day 15 (Post-CAE)	-8.0 (22.37)	-2.4 (19.21)	1.9 (16.56)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-4.9 (27.23)	2.2 (21.18)	0.3 (19.52)
Change from Baseline: Day 29 (Pre-CAE)	-2.7 (24.78)	-9.5 (20.74)	-1.7 (20.97)
Change from Baseline: Day 29 (Post-CAE)	-9.3 (19.47)	-6.2 (23.64)	2.2 (23.30)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-3.6 (15.78)	5.2 (26.67)	3.6 (25.99)
Change from Baseline: Day 57 (Pre-CAE)	-6.8 (22.73)	-8.1 (27.02)	-1.2 (23.65)
Change from Baseline: Day 57 (Post-CAE)	-7.0 (27.35)	-5.7 (23.95)	-2.1 (19.13)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-0.2 (25.65)	4.7 (22.75)	0.2 (26.94)

30. Secondary Outcome

Title	Change From Baseline in Visual Analog Scale (Foreign Body)
Description	Participants rated ocular symptom of foreign body by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	35.3 (25.95)	35.1 (29.19)	34.1 (25.87)
Day 1 Post-CAE	45.1 (29.54)	43.1 (31.03)	49.9 (27.82)
Day 1 (Change from Pre-CAE to Post-CAE)	9.8 (24.25)	8.1 (22.30)	15.8 (21.57)
Change from Baseline: Day 8	-6.2 (23.33)	-3.4 (16.32)	-0.4 (19.69)
Change from Baseline: Day 15 (Pre-CAE)	-7.8 (23.00)	-1.3 (18.83)	-5.0 (17.15)
Change from Baseline: Day 15 (Post-CAE)	-8.5 (20.45)	-0.7 (21.90)	-7.9 (18.96)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-0.6 (28.16)	0.8 (27.76)	-2.8 (20.72)
Change from Baseline: Day 29 (Pre-CAE)	-6.2 (28.69)	-5.0 (16.97)	-5.9 (26.37)
Change from Baseline: Day 29 (Post-CAE)	-8.6 (16.41)	-4.7 (19.58)	-1.1 (20.54)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	1.4 (19.18)	2.6 (19.77)	-0.6 (22.53)
Change from Baseline: Day 57 (Pre-CAE)	-9.3 (21.64)	-7.3 (28.49)	-5.2 (18.58)
Change from Baseline: Day 57 (Post-CAE)	-10.3 (23.81)	-1.5 (27.06)	-8.5 (19.20)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-1.0 (27.77)	6.9 (30.44)	-3.7 (25.32)

31. Secondary Outcome

Title	Change From Baseline in Visual Analog Scale (Blurred Vision)
Description	Participants rated ocular symptom of blurred vision by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	18.5 (22.85)	24.0 (27.00)	26.9 (20.32)
Day 1 Post-CAE	26.4 (28.30)	32.2 (30.82)	41.1 (28.62)
Day 1 (Change from Pre-CAE to Post-CAE)	7.9 (18.33)	8.2 (25.15)	14.2 (20.98)
Change from Baseline: Day 8	2.5 (12.34)	-4.5 (23.77)	-4.2 (15.37)
Change from Baseline: Day 15 (Pre-CAE)	3.7 (11.94)	-2.9 (19.40)	-2.1 (15.80)
Change from Baseline: Day 15 (Post-CAE)	-1.1 (14.37)	-7.3 (24.44)	-8.7 (21.87)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-4.7 (16.88)	-4.4 (23.96)	-6.6 (27.55)
Change from Baseline: Day 29 (Pre-CAE)	-2.0 (14.81)	-4.0 (18.45)	-3.2 (16.29)
Change from Baseline: Day 29 (Post-CAE)	-5.9 (16.34)	-7.9 (23.39)	-6.1 (17.73)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-2.5 (19.24)	-5.4 (21.62)	-7.7 (21.60)
Change from Baseline: Day 57 (Pre-CAE)	0.5 (14.90)	-3.0 (21.79)	-1.2 (19.67)
Change from Baseline: Day 57 (Post-CAE)	-4.0 (19.15)	-6.9 (24.83)	-7.8 (21.29)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-4.5 (17.82)	-3.3 (27.89)	-6.5 (27.14)

32. Secondary Outcome

Title	Change From Baseline in Visual Analog Scale (Dryness)
Description	Participants rated ocular symptom of dryness by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	57.7 (20.98)	58.6 (24.58)	58.0 (22.90)
Day 1 Post-CAE	74.2 (18.66)	71.8 (21.47)	75.0 (18.09)
Day 1 (Change from Pre-CAE to Post-CAE)	16.5 (16.76)	13.3 (17.80)	17.0 (18.30)
Change from Baseline: Day 8	-4.7 (16.31)	-2.1 (14.26)	-1.6 (19.15)
Change from Baseline: Day 15 (Pre-CAE)	-6.7 (19.32)	-7.4 (17.94)	-4.2 (20.52)
Change from Baseline: Day 15 (Post-CAE)	-1.7 (12.82)	-4.5 (16.69)	-1.7 (17.81)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	5.0 (21.30)	3.0 (21.22)	2.5 (22.67)
Change from Baseline: Day 29 (Pre-CAE)	-6.4 (23.40)	-10.3 (19.89)	-7.1 (25.61)
Change from Baseline: Day 29 (Post-CAE)	-5.8 (14.15)	-7.1 (13.36)	-5.1 (12.50)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	2.3 (21.34)	3.5 (20.86)	0.6 (23.70)
Change from Baseline: Day 57 (Pre-CAE)	-11.7 (24.14)	-11.3 (26.02)	-8.4 (26.81)
Change from Baseline: Day 57 (Post-CAE)	-8.3 (15.28)	-3.8 (14.57)	-7.7 (22.21)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	3.3 (25.71)	9.0 (24.83)	1.7 (25.52)

33. Secondary Outcome

Title	Change From Baseline in Visual Analog Scale (Photophobia)
Description	Participants rated ocular symptom of photophobia by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	32.8 (28.41)	37.4 (33.86)	36.7 (29.19)
Day 1 Post-CAE	38.1 (29.80)	39.8 (34.50)	49.7 (32.33)
Day 1 (Change from Pre-CAE to Post-CAE)	5.3 (16.70)	2.2 (21.20)	13.0 (22.01)
Change from Baseline: Day 8	1.4 (16.17)	-5.0 (21.40)	-2.7 (18.46)
Change from Baseline: Day 15 (Pre-CAE)	-1.4 (16.19)	-11.0 (22.36)	-2.1 (18.17)
Change from Baseline: Day 15 (Post-CAE)	-2.4 (14.21)	-5.7 (19.94)	-8.8 (18.47)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-1.0 (19.59)	5.8 (23.32)	-6.7 (22.12)
Change from Baseline: Day 29 (Pre-CAE)	-3.1 (19.61)	-7.3 (28.18)	-3.1 (26.01)
Change from Baseline: Day 29 (Post-CAE)	-4.0 (13.84)	-4.9 (18.11)	-0.9 (18.18)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	3.0 (17.38)	2.1 (13.89)	-2.7 (27.46)
Change from Baseline: Day 57 (Pre-CAE)	-4.1 (20.87)	-3.6 (26.95)	-3.6 (22.33)
Change from Baseline: Day 57 (Post-CAE)	-4.0 (21.66)	-2.3 (20.85)	-10.4 (23.91)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	0.2 (28.34)	1.5 (21.40)	-6.5 (24.53)

34. Secondary Outcome

Title	Change From Baseline in Visual Analog Scale (Pain)
Description	Participants rated ocular symptom of pain by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0 mm corresponds to "no discomfort" and 100 mm corresponds to "maximal discomfort."
Time Frame	Baseline (Day 1 Pre-CAE and Post-CAE), Day 8, Day 15 (Pre-CAE and Post-CAE), Day 29 (Pre-CAE and Post-CAE), and Day 57 (Pre-CAE and Post-CAE)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1 Pre-CAE	17.0 (22.31)	17.8 (23.62)	17.4 (21.01)
Day 1 Post-CAE	29.1 (30.50)	26.3 (29.53)	27.1 (29.83)
Day 1 (Change from Pre-CAE to Post-CAE)	12.1 (19.65)	8.3 (15.81)	9.7 (20.73)
Change from Baseline: Day 8	-2.2 (11.94)	-1.8 (22.41)	-2.6 (13.91)
Change from Baseline: Day 15 (Pre-CAE)	1.8 (20.34)	-3.1 (22.90)	-2.1 (14.54)
Change from Baseline: Day 15 (Post-CAE)	-3.9 (17.59)	-2.0 (16.84)	-2.8 (18.66)
Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE)	-5.7 (19.81)	1.5 (22.96)	-0.8 (23.07)
Change from Baseline: Day 29 (Pre-CAE)	-3.8 (17.30)	-3.3 (20.23)	-3.4 (15.35)
Change from Baseline: Day 29 (Post-CAE)	-8.0 (16.05)	-1.8 (18.57)	-9.9 (18.61)
Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE)	-3.3 (15.38)	7.7 (16.05)	-8.1 (20.05)
Change from Baseline: Day 57 (Pre-CAE)	-0.2 (22.85)	-6.6 (24.80)	-2.8 (14.32)
Change from Baseline: Day 57 (Post-CAE)	-10.9 (16.16)	-4.1 (20.22)	-2.1 (12.68)
Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE)	-10.7 (28.15)	3.9 (21.67)	0.7 (16.52)

35. Secondary Outcome

Title	Change From Baseline in Ocular Surface and Disease Index (OSDI©)
Description	The OSDI is a simple 12-question survey that rates the severity of the participant's dry eye disease based on the symptoms. It is assessed on a scale of 0 to 100, with higher score representing greater disability.
Time Frame	Baseline (Day 1); Days 8, 15, 29, and 57

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 percent (%) ophthalmic solution as topical ophthalmic drops, twice daily (BID) for up to 8 weeks. Exposures to the controlled adverse environment® (CAE) were conducted at Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the controlled adverse environment® (CAE) were conducted at Day 15, Day 29 and Day 57.	Participants sefl-administered HL036 placebo matching vehicle solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the controlled adverse environment® (CAE) were conducted at Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Day 1	32.45 (14.379)	36.78 (18.209)	38.08 (16.602)
Change From Baseline: Day 8	-1.57 (7.885)	-0.87 (7.889)	-3.79 (8.161)
Change From Baseline: Day 15	-0.49 (9.048)	-2.98 (10.361)	-3.65 (10.727)
Change From Baseline: Day 29	-0.92 (10.324)	-4.42 (12.540)	-5.48 (12.471)
Change From Baseline: Day 57	-1.45 (11.598)	-3.33 (11.978)	-5.05 (10.817)

36. Secondary Outcome

Title	Ora Calibra® Drop Comfort Scale
Description	Ora Calibra® drop comfort scale ranges from 0 to 10. A score of 0 indicates comfortable and 10 indicates uncomfortable. Lower score indicated better comfort level.
Time Frame	Upon instillation and 1 and 2 minutes post-instillation on Day 1

Outcome Measure Data

Analysis Population Description

The ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo matching vehicle solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	50	50	50
Upon instillation on Day 1	2.8 (2.25)	3.6 (2.40)	3.3 (2.69)
1 minute post-instillation on Day 1	2.0 (1.86)	2.6 (1.93)	2.3 (1.84)
2 minutes post-instillation on Day 1	1.6 (1.75)	2.3 (1.91)	2.0 (1.89)

37. Secondary Outcome

Title	Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Overall Ocular Discomfort)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of overall ocular discomfort twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.
Time Frame	From Baseline (Day 1) to Day 56

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	47	50	49
Baseline: Daily average	2.74 (0.884)	2.82 (0.934)	2.66 (0.789)
Average Day 1 to Day 7: Change from Baseline Daily Average	-0.13 (0.326)	-0.09 (0.337)	-0.07 (0.376)
Average Day 8 to Day 14: Change from Baseline Daily Average	-0.24 (0.430)	-0.10 (0.442)	-0.09 (0.510)
Average Day 15 to Day 21: Change from Baseline Daily Average	-0.21 (0.534)	-0.19 (0.465)	-0.13 (0.628)
Average Day 22 to Day 28: Change from Baseline Daily Average	-0.23 (0.558)	-0.29 (0.464)	-0.24 (0.650)
Average Day 29 to Day 35: Change from Baseline Daily Average	-0.18 (0.600)	-0.25 (0.548)	-0.15 (0.623)
Average Day 36 to Day 42: Change from Baseline Daily Average	-0.28 (0.597)	-0.28 (0.638)	-0.18 (0.638)
Average Day 43 to Day 49: Change from Baseline Daily Average	-0.34 (0.636)	-0.31 (0.666)	-0.16 (0.662)
Average Day 50 to Day 56: Change from Baseline Daily Average	-0.38 (0.713)	-0.29 (0.658)	-0.16 (0.674)

38. Secondary Outcome

Title	Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Burning)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of burning twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.
Time Frame	From Baseline (Day 1) to Day 56

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	49	50	50
Baseline: Daily average	1.72 (1.126)	1.49 (1.134)	1.50 (1.135)
Average Day 1 to Day 7: Change from Baseline Daily Average	-0.13 (0.309)	-0.08 (0.398)	-0.07 (0.328)
Average Day 8 to Day 14: Change from Baseline Daily Average	-0.26 (0.369)	-0.17 (0.438)	-0.11 (0.420)
Average Day 15 to Day 21: Change from Baseline Daily Average	-0.22 (0.430)	-0.21 (0.498)	-0.12 (0.464)
Average Day 22 to Day 28: Change from Baseline Daily Average	-0.26 (0.449)	-0.29 (0.511)	-0.18 (0.546)
Average Day 29 to Day 35: Change from Baseline Daily Average	-0.18 (0.506)	-0.28 (0.523)	-0.11 (0.511)
Average Day 36 to Day 42: Change from Baseline Daily Average	-0.25 (0.440)	-0.35 (0.701)	-0.17 (0.500)
Average Day 43 to Day 49: Change from Baseline Daily Average	-0.25 (0.565)	-0.33 (0.647)	-0.13 (0.564)
Average Day 50 to Day 56: Change from Baseline Daily Average	-0.27 (0.571)	-0.33 (0.739)	-0.11 (0.527)

39. Secondary Outcome

Title	Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Dryness)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of dryness twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.
Time Frame	From Baseline (Day 1) to Day 56

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	49	50	50
Baseline: Daily average	2.88 (0.793)	2.96 (0.968)	2.99 (0.669)
Average Day 1 to Day 7: Change from Baseline Daily Average	-0.13 (0.391)	-0.11 (0.275)	-0.10 (0.383)
Average Day 8 to Day 14: Change from Baseline Daily Average	-0.20 (0.505)	-0.14 (0.388)	-0.13 (0.504)
Average Day 15 to Day 21: Change from Baseline Daily Average	-0.20 (0.615)	-0.25 (0.479)	-0.13 (0.621)
Average Day 22 to Day 28: Change from Baseline Daily Average	-0.23 (0.620)	-0.30 (0.519)	-0.29 (0.659)
Average Day 29 to Day 35: Change from Baseline Daily Average	-0.17 (0.691)	-0.29 (0.485)	-0.21 (0.690)
Average Day 36 to Day 42: Change from Baseline Daily Average	-0.30 (0.680)	-0.32 (0.628)	-0.23 (0.677)
Average Day 43 to Day 49: Change from Baseline Daily Average	-0.35 (0.728)	-0.31 (0.704)	-0.25 (0.768)
Average Day 50 to Day 56: Change from Baseline Daily Average	-0.40 (0.793)	-0.29 (0.703)	-0.27 (0.812)

40. Secondary Outcome

Title	Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Grittiness)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of grittiness twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.
Time Frame	From Baseline (Day 1) to Day 56

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	49	50	50
Baseline: Daily average	2.14 (0.988)	1.84 (1.248)	2.07 (1.177)
Average Day 1 to Day 7: Change from Baseline Daily Average	-0.19 (0.450)	-0.07 (0.331)	-0.03 (0.407)
Average Day 8 to Day 14: Change from Baseline Daily Average	-0.27 (0.555)	-0.07 (0.500)	-0.08 (0.555)
Average Day 15 to Day 21: Change from Baseline Daily Average	-0.22 (0.594)	-0.16 (0.540)	-0.14 (0.554)
Average Day 22 to Day 28: Change from Baseline Daily Average	-0.26 (0.628)	-0.21 (0.615)	-0.23 (0.655)
Average Day 29 to Day 35: Change from Baseline Daily Average	-0.21 (0.724)	-0.22 (0.554)	-0.18 (0.627)
Average Day 36 to Day 42: Change from Baseline Daily Average	-0.35 (0.682)	-0.18 (0.642)	-0.18 (0.561)
Average Day 43 to Day 49: Change from Baseline Daily Average	-0.38 (0.682)	-0.16 (0.833)	-0.16 (0.666)
Average Day 50 to Day 56: Change from Baseline Daily Average	-0.36 (0.764)	-0.11 (0.959)	-0.18 (0.708)

41. Secondary Outcome

Title	Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Stinging)
Description	Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye includes rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of stinging twice a day in a diary on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. The average of the morning and evening assessments were calculated for each day. Weekly average scores were calculated based on the daily scores in the week.
Time Frame	From Baseline (Day 1) to Day 56

Outcome Measure Data

Analysis Population Description

Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only.

Arm/Group Title	0.10% HL036 Ophthalmic Solution	0.25% HL036 Ophthalmic Solution	Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.	Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
Measure Participants	49	50	50
Baseline: Daily average	1.53 (1.113)	1.20 (1.127)	1.26 (1.075)
Average Day 1 to Day 7: Change from Baseline Daily Average	-0.14 (0.349)	-0.13 (0.327)	-0.11 (0.342)
Average Day 8 to Day 14: Change from Baseline Daily Average	-0.24 (0.409)	-0.12 (0.438)	-0.14 (0.469)
Average Day 15 to Day 21: Change from Baseline Daily Average	-0.16 (0.428)	-0.22 (0.515)	-0.20 (0.455)
Average Day 22 to Day 28: Change from Baseline Daily Average	-0.12 (0.517)	-0.28 (0.533)	-0.24 (0.546)
Average Day 29 to Day 35: Change from Baseline Daily Average	-0.11 (0.572)	-0.28 (0.538)	-0.21 (0.517)
Average Day 36 to Day 42: Change from Baseline Daily Average	-0.22 (0.564)	-0.32 (0.631)	-0.20 (0.514)
Average Day 43 to Day 49: Change from Baseline Daily Average	-0.24 (0.553)	-0.27 (0.647)	-0.16 (0.612)
Average Day 50 to Day 56: Change from Baseline Daily Average	-0.22 (0.575)	-0.28 (0.744)	-0.15 (0.577)

Adverse Events

Time Frame	Baseline up to 8 weeks
Adverse Event Reporting Description	Safety population included all randomized subjects who have received at least one dose of the investigational product.
Arm/Group Title	0.10% HL036 Ophthalmic Solution		0.25% HL036 Ophthalmic Solution		Placebo
Arm/Group Description	Participants self-administered HL036 0.10 % ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.		Participants self-administered HL036 0.25% ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.		Participants self-administered HL036 placebo (vehicle solution) as topical ophthalmic drops, BID for up to 8 weeks. Exposures to the CAE® were conducted at Day 1, Day 15, Day 29 and Day 57.
All Cause Mortality
	0.10% HL036 Ophthalmic Solution		0.25% HL036 Ophthalmic Solution		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)		0/50 (0%)
Serious Adverse Events
	0.10% HL036 Ophthalmic Solution		0.25% HL036 Ophthalmic Solution		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	0.10% HL036 Ophthalmic Solution		0.25% HL036 Ophthalmic Solution		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/50 (26%)		13/50 (26%)		9/50 (18%)
Eye disorders
Conjunctivitis allergic	3/50 (6%)		4/50 (8%)		0/50 (0%)
Visual acuity reduced	3/50 (6%)		0/50 (0%)		0/50 (0%)
General disorders
Instillation site pain	2/50 (4%)		6/50 (12%)		1/50 (2%)
Infections and infestations
Nasopharyngitis	5/50 (10%)		3/50 (6%)		8/50 (16%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.