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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0.10% HL036 Ophthalmic Solution | Experimental | 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. |
|
| 0.25% HL036 Ophthalmic Solution | Experimental | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HL036 ophthalmic solution | Biological | HL036 ophthalmic solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Coprimary Endpoint: Change From Baseline in Inferior Corneal Staining Score to 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. | Baseline (Day 1 Pre-CAE), Day 57 (Pre-CAE) |
| Coprimary Endpoint: Change From Baseline in Ocular Discomfort Score to 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. | Baseline (Day 1 Pre-CAE), Day 57 (Pre-CAE) |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Fluorescein Staining (Inferior Region) | 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. | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gail Torkildsen, MD | Andover Eye Associates | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Central Maine Eye Care | Lewiston | Maine | 04240 | United States | ||
| Andover Eye Associates |
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.
Participants who met all the eligibility criteria were enrolled at 2 sites in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | 0.10% HL036 Ophthalmic Solution | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-treat (ITT) population: The ITT population included all randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | 0.10% HL036 Ophthalmic Solution | 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. |
| BG001 | 0.25% HL036 Ophthalmic Solution |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Coprimary Endpoint: Change From Baseline in Inferior Corneal Staining Score to 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. | ITT Population with the Markov Chain Monte Carlo (MCMC) imputation method for missing values. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1 Pre-CAE), Day 57 (Pre-CAE) |
|
Baseline up to 8 weeks
Safety population included all randomized subjects who have received at least one dose of the investigational product.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 0.10% HL036 Ophthalmic Solution | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctivitis allergic | Eye disorders | MedDRA (20.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Project Manager | Hanall Biopharma | 82-222041763 | parksm@hanall.co.kr |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 31, 2017 | Dec 23, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 15, 2018 | Dec 23, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015352 | Dry Eye Syndromes |
| ID | Term |
|---|---|
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |
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| Placebo vehicle solution | Other | Placebo vehicle solution |
|
| Mean Change From Baseline in Fluorescein Staining (Superior Region) | 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. | 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) |
| Mean Change From Baseline in Fluorescein Staining (Central Region) | 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. | 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) |
| Mean Change From Baseline in Fluorescein Staining (Temporal Region) | 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. | 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) |
| Mean Change From Baseline in Fluorescein Staining (Nasal Region) | 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. | 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) |
| Mean Change From Baseline in Fluorescein Staining (Corneal Sum) | 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. | 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) |
| Mean Change From Baseline in Fluorescein Staining (Conjunctival Sum) | 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. | 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) |
| Mean Change From Baseline in Fluorescein Staining Total Score (All Five Regions: Central, Superior, Inferior, Temporal, Nasal) | 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. | 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) |
| Mean Change From Baseline in Lissamine Green Staining Total Score (Inferior Region) | 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. | 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) |
| Mean Change From Baseline in Lissamine Green Staining Total Score (Superior Region) | 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. | 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) |
| Mean Change From Baseline in Lissamine Green Staining Total Score (Central Region) | 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. | 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) |
| Mean Change From Baseline in Lissamine Green Staining Total Score (Temporal Region) | 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. | 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) |
| Mean Change From Baseline in Lissamine Green Staining Total Score (Nasal Region) | 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. | 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) |
| Mean Change From Baseline in Lissamine Green Staining Total Score (Corneal Sum) | 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. | 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) |
| Mean Change From Baseline in Lissamine Green Staining Total Score (Conjunctival Sum) | 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. | 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) |
| Mean Change From Baseline in Lissamine Green Staining Total Score (All Five Regions: Central, Superior, Inferior, Temporal, Nasal) | 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. | 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) |
| Change From Baseline in Tear Film Break-Up Time | 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. | 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) |
| Change From Baseline in the Ora Calibra® Conjunctival Redness Scale | 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 | 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) |
| Change From Baseline in Schirmer's Test | 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. | Baseline (Day 1); Days 15, 29, and 57 |
| Change From Baseline in Ora Calibra® Ocular Discomfort Scale | 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. | 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) |
| Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Overall Ocular Discomfort) | 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. | 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) |
| Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Burning) | 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. | 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) |
| Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Dryness) | 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. | 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) |
| Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Grittiness) | 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. | 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) |
| Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Stinging) | 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. | 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) |
| Change From Baseline in Visual Analog Scale (Burning) | 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." | 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) |
| Change From Baseline in Visual Analog Scale (Itching) | 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." | 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) |
| Change From Baseline in Visual Analog Scale (Foreign Body) | 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." | 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) |
| Change From Baseline in Visual Analog Scale (Blurred Vision) | 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." | 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) |
| Change From Baseline in Visual Analog Scale (Dryness) | 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." | 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) |
| Change From Baseline in Visual Analog Scale (Photophobia) | 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." | 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) |
| Change From Baseline in Visual Analog Scale (Pain) | 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." | 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) |
| Change From Baseline in Ocular Surface and Disease Index (OSDI©) | 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. | Baseline (Day 1); Days 8, 15, 29, and 57 |
| Ora Calibra® Drop Comfort Scale | 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. | Upon instillation and 1 and 2 minutes post-instillation on Day 1 |
| Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Overall Ocular Discomfort) | 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. | From Baseline (Day 1) to Day 56 |
| Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Burning) | 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. | From Baseline (Day 1) to Day 56 |
| Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Dryness) | 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. | From Baseline (Day 1) to Day 56 |
| Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Grittiness) | 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. | From Baseline (Day 1) to Day 56 |
| Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Stinging) | 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. | From Baseline (Day 1) to Day 56 |
| Andover |
| Massachusetts |
| 01810 |
| United States |
| Administrative Reasons |
|
| Hypertension Not Controlled |
|
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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
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. |
| OG002 | Placebo | 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. |
|
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| Primary | Coprimary Endpoint: Change From Baseline in Ocular Discomfort Score to 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. | ITT Population with the MCMC imputation method for missing values. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1 Pre-CAE), Day 57 (Pre-CAE) |
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| Secondary | Mean Change From Baseline in Fluorescein Staining (Inferior Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Fluorescein Staining (Superior Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Fluorescein Staining (Central Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Fluorescein Staining (Temporal Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Fluorescein Staining (Nasal Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Fluorescein Staining (Corneal Sum) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Fluorescein Staining (Conjunctival Sum) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Fluorescein Staining Total Score (All Five Regions: Central, Superior, Inferior, Temporal, Nasal) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Lissamine Green Staining Total Score (Inferior Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Lissamine Green Staining Total Score (Superior Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Lissamine Green Staining Total Score (Central Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Lissamine Green Staining Total Score (Temporal Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Lissamine Green Staining Total Score (Nasal Region) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Lissamine Green Staining Total Score (Corneal Sum) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Lissamine Green Staining Total Score (Conjunctival Sum) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Mean Change From Baseline in Lissamine Green Staining Total Score (All Five Regions: Central, Superior, Inferior, Temporal, Nasal) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Change From Baseline in Tear Film Break-Up Time | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | seconds | 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) |
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| Secondary | Change From Baseline in the Ora Calibra® Conjunctival Redness Scale | 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 | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Change From Baseline in Schirmer's Test | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | mm | Baseline (Day 1); Days 15, 29, and 57 |
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| Secondary | Change From Baseline in Ora Calibra® Ocular Discomfort Scale | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Overall Ocular Discomfort) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Burning) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Dryness) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Grittiness) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Stinging) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a 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) |
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| Secondary | Change From Baseline in Visual Analog Scale (Burning) | 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." | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | mm | 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) |
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| Secondary | Change From Baseline in Visual Analog Scale (Itching) | 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." | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | mm | 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) |
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| Secondary | Change From Baseline in Visual Analog Scale (Foreign Body) | 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." | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | mm | 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) |
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| Secondary | Change From Baseline in Visual Analog Scale (Blurred Vision) | 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." | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | mm | 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) |
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| Secondary | Change From Baseline in Visual Analog Scale (Dryness) | 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." | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | mm | 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) |
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| Secondary | Change From Baseline in Visual Analog Scale (Photophobia) | 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." | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | mm | 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) |
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| Secondary | Change From Baseline in Visual Analog Scale (Pain) | 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." | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | mm | 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) |
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| Secondary | Change From Baseline in Ocular Surface and Disease Index (OSDI©) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1); Days 8, 15, 29, and 57 |
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| Secondary | Ora Calibra® Drop Comfort Scale | 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. | The ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a scale | Upon instillation and 1 and 2 minutes post-instillation on Day 1 |
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| Secondary | Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Overall Ocular Discomfort) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a scale | From Baseline (Day 1) to Day 56 |
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| Secondary | Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Burning) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a scale | From Baseline (Day 1) to Day 56 |
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| Secondary | Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Dryness) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a scale | From Baseline (Day 1) to Day 56 |
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| Secondary | Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Grittiness) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a scale | From Baseline (Day 1) to Day 56 |
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| Secondary | Daily Diary: Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire for Dry Eye (Stinging) | 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. | Number of participants analyzed included participants in ITT Population with available data. The analysis was carried out with observed data only. | Posted | Mean | Standard Deviation | score on a scale | From Baseline (Day 1) to Day 56 |
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| 0 |
| 50 |
| 0 |
| 50 |
| 13 |
| 50 |
| EG001 | 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. | 0 | 50 | 0 | 50 | 13 | 50 |
| EG002 | 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. | 0 | 50 | 0 | 50 | 9 | 50 |
| Visual acuity reduced | Eye disorders | MedDRA (20.1) | Non-systematic Assessment |
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| Instillation site pain | General disorders | MedDRA (20.1) | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (20.1) | Non-systematic Assessment |
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Not provided
Not provided
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| 0.2321 |
P-value calculated using a model with treatment, baseline score, and site as covariates. |
| LS Mean Difference |
| -0.3 |
| 2-Sided |
| 95 |
| -0.7 |
| 0.2 |
| Superiority |
| ANCOVA | 0.8217 | P-value calculated using a model with treatment, baseline score, and site as covariates. | LS Mean Difference | 0.0 | 2-Sided | 95 | -0.4 | 0.5 | Other |
| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
|
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
|
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
|
| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
|
| Change from Baseline: Day 15 (Post-CAE) |
|
|
| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
|
| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Change From Baseline: Day 15 |
|
|
| Change From Baseline: Day 29 |
|
|
| Change From Baseline: Day 57 |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
|
| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
|
| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
|
| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
|
| Change from Baseline: Day 15 (Post-CAE) |
|
|
| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
|
| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
|
| Change from Baseline: Day 15 (Post-CAE) |
|
|
| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
|
| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
|
| Change from Baseline: Day 15 (Post-CAE) |
|
|
| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 29 (Pre-CAE) |
|
|
| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
|
| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
|
| Change from Baseline: Day 15 (Post-CAE) |
|
|
| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 29 (Pre-CAE) |
|
|
| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
|
| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
|
| Change from Baseline: Day 15 (Post-CAE) |
|
|
| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
|
| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
|
| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
|
| Change from Baseline: Day 15 (Post-CAE) |
|
|
| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
|
|
| Day 1 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
|
| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 29 (Pre-CAE) |
|
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| Change from Baseline: Day 29 (Post-CAE) |
|
|
| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
|
|
| Change from Baseline: Day 57 (Pre-CAE) |
|
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| Change from Baseline: Day 57 (Post-CAE) |
|
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
|
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| Day 1 Post-CAE |
|
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| Day 1 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 8 |
|
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| Change from Baseline: Day 15 (Pre-CAE) |
|
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| Change from Baseline: Day 15 (Post-CAE) |
|
|
| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
|
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
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| Day 1 Post-CAE |
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| Day 1 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 8 |
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| Change from Baseline: Day 15 (Pre-CAE) |
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| Change from Baseline: Day 15 (Post-CAE) |
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| Change from baseline: Day 15 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 29 (Pre-CAE) |
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| Change from Baseline: Day 29 (Post-CAE) |
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| Change from baseline: Day 29 (Change from Pre-CAE to Post-CAE) |
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| Change from Baseline: Day 57 (Pre-CAE) |
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| Change from Baseline: Day 57 (Post-CAE) |
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| Change from baseline: Day 57 (Change from Pre-CAE to Post-CAE) |
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| Change From Baseline: Day 8 |
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| Change From Baseline: Day 15 |
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| Change From Baseline: Day 29 |
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| Change From Baseline: Day 57 |
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| 2 minutes post-instillation on Day 1 |
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| Average Day 1 to Day 7: Change from Baseline Daily Average |
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| Average Day 8 to Day 14: Change from Baseline Daily Average |
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| Average Day 15 to Day 21: Change from Baseline Daily Average |
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| Average Day 22 to Day 28: Change from Baseline Daily Average |
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| Average Day 29 to Day 35: Change from Baseline Daily Average |
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| Average Day 36 to Day 42: Change from Baseline Daily Average |
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| Average Day 43 to Day 49: Change from Baseline Daily Average |
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| Average Day 50 to Day 56: Change from Baseline Daily Average |
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| Average Day 1 to Day 7: Change from Baseline Daily Average |
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| Average Day 8 to Day 14: Change from Baseline Daily Average |
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| Average Day 15 to Day 21: Change from Baseline Daily Average |
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| Average Day 22 to Day 28: Change from Baseline Daily Average |
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| Average Day 29 to Day 35: Change from Baseline Daily Average |
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| Average Day 36 to Day 42: Change from Baseline Daily Average |
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| Average Day 43 to Day 49: Change from Baseline Daily Average |
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| Average Day 50 to Day 56: Change from Baseline Daily Average |
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| Average Day 1 to Day 7: Change from Baseline Daily Average |
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| Average Day 8 to Day 14: Change from Baseline Daily Average |
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| Average Day 15 to Day 21: Change from Baseline Daily Average |
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| Average Day 22 to Day 28: Change from Baseline Daily Average |
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| Average Day 29 to Day 35: Change from Baseline Daily Average |
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| Average Day 36 to Day 42: Change from Baseline Daily Average |
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| Average Day 43 to Day 49: Change from Baseline Daily Average |
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| Average Day 50 to Day 56: Change from Baseline Daily Average |
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| Average Day 1 to Day 7: Change from Baseline Daily Average |
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| Average Day 8 to Day 14: Change from Baseline Daily Average |
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| Average Day 15 to Day 21: Change from Baseline Daily Average |
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| Average Day 22 to Day 28: Change from Baseline Daily Average |
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| Average Day 29 to Day 35: Change from Baseline Daily Average |
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| Average Day 36 to Day 42: Change from Baseline Daily Average |
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| Average Day 43 to Day 49: Change from Baseline Daily Average |
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| Average Day 50 to Day 56: Change from Baseline Daily Average |
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| Average Day 1 to Day 7: Change from Baseline Daily Average |
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| Average Day 8 to Day 14: Change from Baseline Daily Average |
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| Average Day 15 to Day 21: Change from Baseline Daily Average |
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| Average Day 22 to Day 28: Change from Baseline Daily Average |
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| Average Day 29 to Day 35: Change from Baseline Daily Average |
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| Average Day 36 to Day 42: Change from Baseline Daily Average |
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| Average Day 43 to Day 49: Change from Baseline Daily Average |
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| Average Day 50 to Day 56: Change from Baseline Daily Average |
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