A Study to Assess Efficacy of HL036 in Subjects With Dry Eyes

Phase 2

Completed

Conditions: Dry Eye

Interventions: Biological: HL036 ophthalmic solution
Other: Placebo vehicle solution

Registration Number: NCT03334539

Lead Sponsor: HanAll BioPharma Co., Ltd.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 150

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
0.10% HL036 Ophthalmic Solution	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.
Placebo	Placebo vehicle solution	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.
0.25% HL036 Ophthalmic Solution	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.

Primary Outcome Measures

Name	Time	Method
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® Corneal and Conjunctival staining scale. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement.
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

Name	Time	Method
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® Corneal 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.
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® Corneal 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.
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® Corneal 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.
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® Corneal 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.
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® Corneal and Conjunctival staining scale. Individual region score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Conjunctival sum score ranges from 0 to 8. Change score from pre- to post-CAE® was calculated as post-CAE® score - pre-CAE® score.
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.
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® Corneal 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.
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.
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.
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.
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® Corneal 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.
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.
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.
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.
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.
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® Corneal 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.
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.
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."
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.
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."
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.
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
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.
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."
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.
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.
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.
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."
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."
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.
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.
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.
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.
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.
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."
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."
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.
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.
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.