Trial Outcomes & Findings for Tolerability, Safety and Efficacy of Lubricin Versus Sodium Hyaluronate Eye Drops in Patients With Moderate Dry Eye (NCT NCT02507934)

Last Updated: 2024-10-15

Results Overview

A global ocular tolerability score was determined using a 100 mm Visual Analogue Scale (VAS) on which 0 meant no symptoms and 100 meant the worst possible discomfort. This evaluation was to be performed before any ophthalmic assessment at each scheduled visit. Specific ocular symptoms were measured with the VAS included: foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia. The patients evaluated their symptoms using the VAS giving the value they were feeling from none to an extreme value. The VAS scale was a straight horizontal line of fixed length (100 mm). The ends were defined as the extreme limits of the parameter. Please note that Ophthalmological evaluations were performed for both eyes. Hence both the eyes - right and left - were "study-eyes".

Recruitment status

COMPLETED

Study phase

Target enrollment

40 participants

Primary outcome timeframe

Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

Results posted on

2024-10-15

Participant Flow

Participant milestones

Participant milestones
Measure	Lubricin 150 μg/ml Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Overall Study STARTED	20	20
Overall Study Full Analysis Set Population (FAS)	19	20
Overall Study Safety Population (SAF)	20	20
Overall Study COMPLETED	16	20
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Lubricin 150 μg/ml Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Tolerability, Safety and Efficacy of Lubricin Versus Sodium Hyaluronate Eye Drops in Patients With Moderate Dry Eye

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops	Total n=39 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	11 Participants n=7 Participants	28 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	51.9 years STANDARD_DEVIATION 11.8 • n=5 Participants	61.8 years STANDARD_DEVIATION 13.3 • n=7 Participants	56.8 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Italy	19 participants n=5 Participants	20 participants n=7 Participants	39 participants n=5 Participants

PRIMARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

Population: The Full Analysis Set (FAS) population included all enrolled subjects, who received at least one dose of the IMD (Lubricin or Vismed®) during the treatment phase. This analysis set was used for the efficacy analysis. Data in the FAS are analyzed for each eye, left and right respectively. Each eye contributes to the analysis without having defined a study eye.

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Burning /Stinging - Right eye - Day 21±1	-35.7 mm Standard Deviation 25.8	-32.9 mm Standard Deviation 24.6
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Foreign body sensation - Left eye - Day 7±1	-29.3 mm Standard Deviation 27.1	-16.6 mm Standard Deviation 24.4
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Foreign body sensation - Right eye - Day 7±1	-28.4 mm Standard Deviation 29.0	-20.7 mm Standard Deviation 22.4
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Foreign body sensation - Left eye - Day 14±1	-38.9 mm Standard Deviation 23.8	-23.6 mm Standard Deviation 25.6
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Foreign body sensation - Right eye - Day 14±1	-35.9 mm Standard Deviation 23.1	-24.2 mm Standard Deviation 23.1
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Foreign body sensation - Left eye - Day 21±1	-32.7 mm Standard Deviation 29.4	-23.0 mm Standard Deviation 23.7
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Foreign body sensation - Right eye - Day 21±1	-32.3 mm Standard Deviation 26.3	-23.3 mm Standard Deviation 21.3
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Burning /Stinging - Left eye - Day 7±1	-32.1 mm Standard Deviation 30.9	-23.5 mm Standard Deviation 21.3
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Burning /Stinging - Right eye - Day 7±1	-29.2 mm Standard Deviation 28.7	-27.3 mm Standard Deviation 22.1
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Burning /Stinging - Left eye - Day 14±1	-41.9 mm Standard Deviation 26.8	-31.0 mm Standard Deviation 24.4
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Burning /Stinging - Right eye - Day 14±1	-37.9 mm Standard Deviation 27.2	-33.8 mm Standard Deviation 25.3
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Burning /Stinging - Left eye - Day 21±1	-41.2 mm Standard Deviation 27.6	-29.5 mm Standard Deviation 24.6
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Itching - Left eye - Day 7±1	-26.2 mm Standard Deviation 30.6	-18.2 mm Standard Deviation 22.4
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Itching - Right eye - Day 7±1	-18.4 mm Standard Deviation 22.3	-25.3 mm Standard Deviation 27.2
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Itching - Left eye - Day 14±1	-22.5 mm Standard Deviation 21.7	-31.3 mm Standard Deviation 27.00
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Itching - Right eye - Day 14±1	-22.7 mm Standard Deviation 23.2	-28.5 mm Standard Deviation 26.1
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Itching - Left eye - Day 21±1	-21.7 mm Standard Deviation 20.2	-32.5 mm Standard Deviation 24.6
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Itching - Right eye - Day 21±1	-21.9 mm Standard Deviation 23.3	-29.2 mm Standard Deviation 23.4
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Pain - Left eye - Day 7±1	-10.1 mm Standard Deviation 15.2	-21.0 mm Standard Deviation 29.2
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Pain - Right eye - Day 7±1	-7.4 mm Standard Deviation 17.3	-21.6 mm Standard Deviation 26.4
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Pain - Left eye - Day 14±1	-12.4 mm Standard Deviation 15.6	-22.9 mm Standard Deviation 26.1
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Pain - Right eye - Day 14±1	-11.3 mm Standard Deviation 16.6	-24.9 mm Standard Deviation 27.3
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Pain - Left eye - Day 21±1	-12.3 mm Standard Deviation 16.9	-26.6 mm Standard Deviation 24.0
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Pain - Right eye - Day 21±1	-14.3 mm Standard Deviation 15.8	-25.7 mm Standard Deviation 26.7
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Sticky feeling - Left eye - Day 7±1	-28.5 mm Standard Deviation 28.0	-17.1 mm Standard Deviation 25.3
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Sticky feeling - Right eye - Day 7±1	-33.1 mm Standard Deviation 27.8	-18.0 mm Standard Deviation 21.4
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Sticky feeling - Left eye - Day 14±1	-33.1 mm Standard Deviation 30.5	-21.9 mm Standard Deviation 23.6
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Sticky feeling - Right eye - Day 14±1	-35.9 mm Standard Deviation 26.5	-20.1 mm Standard Deviation 19.3
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Sticky feeling - Left eye - Day 21±1	-31.7 mm Standard Deviation 30.8	-20.2 mm Standard Deviation 26.5
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Sticky feeling - Right eye - Day 21±1	-37.3 mm Standard Deviation 26.5	-19.4 mm Standard Deviation 22.4
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Blurred vision - Left eye - Day 7±1	-36.1 mm Standard Deviation 30.4	-22.7 mm Standard Deviation 21.8
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Blurred vision - Right eye - Day 7±1	-28.4 mm Standard Deviation 31.6	-27.9 mm Standard Deviation 26.2
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Blurred vision - Left eye - Day 14±1	-34.9 mm Standard Deviation 25.7	-27.2 mm Standard Deviation 19.5
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Blurred vision - Right eye - Day 14±1	-27.7 mm Standard Deviation 24.9	-29.0 mm Standard Deviation 22.5
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Blurred vision - Left eye - Day 21±1	-37.7 mm Standard Deviation 29.4	-28.7 mm Standard Deviation 22.6
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Blurred vision - Right eye - Day 21±1	-33.3 mm Standard Deviation 26.1	-33.1 mm Standard Deviation 24.9
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Photophobia - Left eye - Day 7±1	-34.9 mm Standard Deviation 33.0	-26.5 mm Standard Deviation 26.3
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Photophobia - Right eye - Day 7±1	-35.2 mm Standard Deviation 29.9	-28.0 mm Standard Deviation 25.0
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Photophobia - Left eye - Day 14±1	-37.0 mm Standard Deviation 30.0	-29.3 mm Standard Deviation 27.0
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Photophobia - Right eye - Day 14±1	-38.6 mm Standard Deviation 27.2	-30.5 mm Standard Deviation 23.6
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Photophobia - Left eye - Day 21 ±1	-42.2 mm Standard Deviation 34.2	-30.8 mm Standard Deviation 28.0
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Photophobia - Right eye - Day 21±1	-39.1 mm Standard Deviation 28.3	-32.1 mm Standard Deviation 27.6
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Total - Left eye - Day 7±1	-189.1 mm Standard Deviation 119.1	-153.5 mm Standard Deviation 129.1
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Total - Right eye - Day 7±1	-179.9 mm Standard Deviation 115.9	-168.7 mm Standard Deviation 117.3
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Total - Left eye - Day 14±1	-220.6 mm Standard Deviation 121.1	-187.0 mm Standard Deviation 115.3
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Total - Right eye - Day 14±1	-209.9 mm Standard Deviation 112.4	-190.9 mm Standard Deviation 99.7
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Total - Left eye - Day 21±1	-219.5 mm Standard Deviation 137.7	-191.1 mm Standard Deviation 127.4
Change From Baseline in Foreign Body Sensation, Burning/Stinging, Itching, Pain, Stick Feeling, Blurred Vision, Photophobia and Total Ocular Tolerability Score (VAS) Total - Right eye - Day 21±1	-213.9 mm Standard Deviation 119.9	-195.6 mm Standard Deviation 115.9

PRIMARY outcome

Timeframe: Visit 5/Final visit/Follow up - Day 21±1

Population: The Safety population (SAF)included all subjects who receive at least one dose of the IMDs (Lubricin or Vismed®).

TEAEs included all AEs occurring or worsening after the first dose of the IMD. These comprise AEs during the treatment and follow-up period. For TEAE the number of events was provided.

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=20 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Treatment-emergent Adverse Events (TEAEs), Assessed Throughout the Study. All TEAEs	3 number of events	2 number of events
Treatment-emergent Adverse Events (TEAEs), Assessed Throughout the Study. TEAEs - Related to treatment	0 number of events	0 number of events
Treatment-emergent Adverse Events (TEAEs), Assessed Throughout the Study. TEAEs - Not related to treatment	3 number of events	2 number of events
Treatment-emergent Adverse Events (TEAEs), Assessed Throughout the Study. TEAEs - Mild	3 number of events	2 number of events
Treatment-emergent Adverse Events (TEAEs), Assessed Throughout the Study. TEAEs - Moderate	0 number of events	0 number of events
Treatment-emergent Adverse Events (TEAEs), Assessed Throughout the Study. TEAEs - Severe	0 number of events	0 number of events
Treatment-emergent Adverse Events (TEAEs), Assessed Throughout the Study. Serious TEAEs	0 number of events	0 number of events
Treatment-emergent Adverse Events (TEAEs), Assessed Throughout the Study. TEAEs - Leading to discontinuation	0 number of events	0 number of events

SECONDARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

The corneal fluorescein staining was graded by using the Oxford scheme to assess cornea and conjunctiva epithelium damage. The Oxford grading scale divides corneal staining into six groups according to severity from 0 (absent) to 5 (severe). The examiner compared the overall appearance of the patient's corneal staining with a reference figure, simulating the pattern of staining encountered in dry eye disease. No attempt was made to count the dots or to assess the position or confluence of the dots. The examiner selected the appropriate grade that best represented the state of corneal staining. The grading system recommended by NEI divides the cornea into five zones (central, superior, temporal, nasal, and inferior) and for each zone, the severity of corneal fluorescein staining is graded on a scale from 0 to 3 based on reference figures. Therefore, the maximum score (worst outcome) was 15, the minimum (best outcome) was 0. Please note: both the eyes, right \& left, were "study-eyes".

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in Corneal Fluorescein Surface Staining (Oxford Score) Left eye - Day 7±1	-0.8 score on a scale Standard Deviation 0.6	-0.6 score on a scale Standard Deviation 0.5
Change From Baseline in Corneal Fluorescein Surface Staining (Oxford Score) Right eye - Day 7±1	-0.7 score on a scale Standard Deviation 0.8	-0.9 score on a scale Standard Deviation 0.8
Change From Baseline in Corneal Fluorescein Surface Staining (Oxford Score) Left eye - Day 14±1	-1.4 score on a scale Standard Deviation 1.1	-0.7 score on a scale Standard Deviation 0.6
Change From Baseline in Corneal Fluorescein Surface Staining (Oxford Score) Right eye - Day 14±1	-1.5 score on a scale Standard Deviation 0.8	-0.9 score on a scale Standard Deviation 0.9
Change From Baseline in Corneal Fluorescein Surface Staining (Oxford Score) Left eye - Day 21±1	-1.8 score on a scale Standard Deviation 1.1	-0.8 score on a scale Standard Deviation 0.9
Change From Baseline in Corneal Fluorescein Surface Staining (Oxford Score) Right eye - Day 21±1	-1.8 score on a scale Standard Deviation 0.8	-1.1 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

Population: The Full Analysis Set (FAS) population included all enrolled subjects, who received at least one dose of the IMD (Lubricin or Vismed®) during the treatment phase. Data in the FAS are analyzed for each eye, left and right respectively. Each eye contributes to the analysis without having defined a study eye.

The Schirmer test type I (without anaesthesia) was performed to measure aqueous tear secretion prior to the instillation of any dilating or anaesthetic eye drops.The rounded bent end of a sterile strip was inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes had elapsed, the Schirmer"s test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). Changes from baseline in values of Schirmer's test type I were summarised by eye and evaluation visit, and stratified by severity level. The longer the wetted length, the healthier the status of the eye. Please note that Ophthalmological evaluations were performed for both eyes. Hence both the eyes - right and left - were "study-eyes".

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in Schirmer Test I (Without Anaesthesia) Left eye - Day 7±1	0.8 score on a scale Standard Deviation 1.3	1.4 score on a scale Standard Deviation 2.3
Change From Baseline in Schirmer Test I (Without Anaesthesia) Right eye - Day 7±1	1.0 score on a scale Standard Deviation 3.0	0.8 score on a scale Standard Deviation 2.2
Change From Baseline in Schirmer Test I (Without Anaesthesia) Left eye - Day 14±1	1.4 score on a scale Standard Deviation 1.4	1.4 score on a scale Standard Deviation 2.1
Change From Baseline in Schirmer Test I (Without Anaesthesia) Right eye - Day 14±1	1.8 score on a scale Standard Deviation 3.9	0.5 score on a scale Standard Deviation 2.5
Change From Baseline in Schirmer Test I (Without Anaesthesia) Left eye - Day 21±1	1.4 score on a scale Standard Deviation 2.2	0.3 score on a scale Standard Deviation 3.2
Change From Baseline in Schirmer Test I (Without Anaesthesia) Right eye - Day 21±1	1.6 score on a scale Standard Deviation 4.1	0.4 score on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

The SANDE (Symptom Assessment in Dry Eye) questionnaire was a short questionnaire to evaluate both dry eye frequency and severity by using a 100 mm VAS. For the assessment, the subjects marked on the 100 mm VAS line the point that they felt represented their perception of their current state. The VAS score was determined by measuring in millimetres from the left hand end of the line to the point that the subject marked. The SANDE scores was then evaluated for the 2 questions severity (0-100) and frequency (0-100), where 0 was the best condition and 100 marked the worst condition. Please note that ophthalmological evaluations were performed for both eyes. Hence both the eyes - right and left - were "study-eyes".

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in SANDE (Symptom Assessment in Dry Eye) - Frequency of Symptoms Day 7±1	-29.6 mm Standard Deviation 31.8	-18.4 mm Standard Deviation 17.8
Change From Baseline in SANDE (Symptom Assessment in Dry Eye) - Frequency of Symptoms Day 14±1	-39.6 mm Standard Deviation 29.3	-21.4 mm Standard Deviation 22.7
Change From Baseline in SANDE (Symptom Assessment in Dry Eye) - Frequency of Symptoms Day 21±1	-39.7 mm Standard Deviation 30.9	-16.2 mm Standard Deviation 22.5

SECONDARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

The SANDE (Symptom Assessment in Dry Eye) questionnaire was a short questionnaire to evaluate both dry eye severity and frequency by using a 100 mm VAS. For the assessment, the subjects marked on the 100 mm VAS line the point that they felt represented their perception of their current state. The VAS score was determined by measuring in millimetres from the left hand end of the line to the point that the subject marked. The SANDE scores were evaluated for the 2 questions severity (0-100) and frequency (0-100), where 0 was the best condition and 100 marked the worst condition. Please note that ophthalmological evaluations were performed for both eyes. Hence both the eyes - right and left - were "study-eyes".

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in SANDE (Symptom Assessment in Dry Eye) - Severity of Symptoms Day 7±1	-25.1 mm Standard Deviation 31.2	-20.7 mm Standard Deviation 2.03
Change From Baseline in SANDE (Symptom Assessment in Dry Eye) - Severity of Symptoms Day 14±1	-37.0 mm Standard Deviation 26.5	-24.3 mm Standard Deviation 19.2
Change From Baseline in SANDE (Symptom Assessment in Dry Eye) - Severity of Symptoms Day 21±1	-35.8 mm Standard Deviation 29.1	-22.4 mm Standard Deviation 19.3

SECONDARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

OPI was used to quantify the interaction between tear film break-up time and blink intervals of a subject. It was based on the idea that, even when the TBUT was normal, if the blink interval was too slow it may cause breakage of tear film due to increased evaporation. The OPI was calculated by dividing TFBUT by inter blink interval (IBI). A visual count of the number of blinks per minute was performed while the subject read the ETDRS chart. ETDRS charts had five Sloan letters on each line; the lines were of equal difficulty, and there was a geometric progression in letter size from line to line. If the IBI and TBUT was same, dividing both give a value of 1.0. If TFBUT was more than IBI, dividing both, gave a value more than 1.0, so dryness would not occur. If TFBUT was less than IBI, dividing both gave a value less than 1.0. A subject was at risk of developing dry eye if the OPI was \< 1.0; so the higher the score the better the outcome. Both eyes - right and left - were "study-eyes".

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in OPI (Ocular Protection Index) Left eye - Day 7±1	0.1 score on a scale Standard Deviation 1.0	0.3 score on a scale Standard Deviation 0.8
Change From Baseline in OPI (Ocular Protection Index) Right eye - Day 7±1	0.1 score on a scale Standard Deviation 0.8	0.4 score on a scale Standard Deviation 0.7
Change From Baseline in OPI (Ocular Protection Index) Left eye - Day 14±1	0.2 score on a scale Standard Deviation 0.9	0.0 score on a scale Standard Deviation 0.8
Change From Baseline in OPI (Ocular Protection Index) Right eye - Day 14±1	0.3 score on a scale Standard Deviation 1.1	0.0 score on a scale Standard Deviation 0.9
Change From Baseline in OPI (Ocular Protection Index) Left eye - Day 21±1	0.2 score on a scale Standard Deviation 0.8	-0.2 score on a scale Standard Deviation 0.8
Change From Baseline in OPI (Ocular Protection Index) Right eye - Day 21±1	0.3 score on a scale Standard Deviation 1.1	-0.1 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

TFBUT was measured by determining the time to tear break-up. The TFBUT test was performed after instillation of 5 µl of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. With the aid of a slit lamp at 10X magnification using cobalt blue illumination, the examiner monitored the integrity of the tear film, noting the time it took to form lacunae (clear spaces in the tear film) from the time that the eye was opened after the last blink. This measurement was performed within 10 seconds maximum. The TFBUT was measured twice during the first minute after the instillation of the fluorescein. If the 2 readings differed by more than 2 seconds, a third reading was taken. The TFBUT value was the average of the 2 or 3 measurements. Generally, a TFBUT value of 10-35 seconds was considered normal. A value of less than 10 seconds was usually suspicious and may indicate tear film instability. Both the eyes - right and left - were "study-eyes".

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in TFBUT (Tear Film Break Up Time) Left eye - Day 7±1	1.8 sec Standard Deviation 2.4	1.2 sec Standard Deviation 1.9
Change From Baseline in TFBUT (Tear Film Break Up Time) Right eye - Day 7±1	1.2 sec Standard Deviation 2.3	1.5 sec Standard Deviation 1.8
Change From Baseline in TFBUT (Tear Film Break Up Time) Left eye - Day 14±1	2.7 sec Standard Deviation 2.4	0.7 sec Standard Deviation 2.1
Change From Baseline in TFBUT (Tear Film Break Up Time) Right eye - Day 14±1	1.9 sec Standard Deviation 2.4	0.6 sec Standard Deviation 2.3
Change From Baseline in TFBUT (Tear Film Break Up Time) Left eye - Day 21±1	2.6 sec Standard Deviation 2.8	0.1 sec Standard Deviation 2.0
Change From Baseline in TFBUT (Tear Film Break Up Time) Right eye - Day 21±1	2.1 sec Standard Deviation 2.9	0.2 sec Standard Deviation 2.4

SECONDARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

BCDVA was determined by careful refraction according to the standard protocol for refraction. Chart 1 was used for testing the VA of the right eye; Chart 2 for the left eye; and Chart R for refraction only. Retroilluminated standard Early Treatment of Diabetic Retinopathy Study (ETDRS) charts were used. They had 5 Sloan letters on each line of equal difficulty, and there was a geometric progression in letter size from line to line.VAS awarded one point for every letter correctly guessed. A distance of 4 meters (m) was required between the subject's eyes and the VA chart. When a subject cannot read at least 20 letters on the chart at 4 m, the subject was tested at 1 m. If 20 or more letters were read at 4 m, the VAS for that eye was recorded as the no of letters correct at 4 m plus 30. Otherwise, the VAS was the no of letters read correctly at 1 m plus the no read at 4 m. The higher the score the better the outcome. Both eyes - right and left - were "study-eyes".

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in BCDVA (Best-corrected Distance Visual Acuity) - ETDRS Score Left eye - Day 7±1	0.2 score on a scale Standard Deviation 0.9	-0.1 score on a scale Standard Deviation 0.3
Change From Baseline in BCDVA (Best-corrected Distance Visual Acuity) - ETDRS Score Right eye - Day 7±1	0.3 score on a scale Standard Deviation 0.6	0.1 score on a scale Standard Deviation 0.6
Change From Baseline in BCDVA (Best-corrected Distance Visual Acuity) - ETDRS Score Left eye - Day 14±1	-1.7 score on a scale Standard Deviation 7.8	-0.1 score on a scale Standard Deviation 0.8
Change From Baseline in BCDVA (Best-corrected Distance Visual Acuity) - ETDRS Score Right eye - Day 14±1	-1.0 score on a scale Standard Deviation 8.0	0.2 score on a scale Standard Deviation 1.0
Change From Baseline in BCDVA (Best-corrected Distance Visual Acuity) - ETDRS Score Left eye - Day 21±1	1.1 score on a scale Standard Deviation 1.8	-0.1 score on a scale Standard Deviation 1.2
Change From Baseline in BCDVA (Best-corrected Distance Visual Acuity) - ETDRS Score Right eye - Day 21±1	0.9 score on a scale Standard Deviation 2.2	0.0 score on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

The Slit Lamp Examination was used to examine the structures of the eye (eyelids, lashes, conjunctiva, cornea, lens, iris and anterior chamber) according to different scales: Eyelid - Meibomian glands (from 0-none to 3-severe), Eyelid - Erythema (from 0-none to 4-very severe), Eyelid - Oedema (from 0-none to 4-very severe), Lashes (0-normal 1-abnormal), Conjunctiva - Erythema (from 0-none to 3-severe), Conjunctiva - Oedema (from 0-none to 4-very severe), Lens (from 0-no opacification to 3-severe lens opacification), Iris (0-normal 1-abnormal), Anterior chamber inflammation (from 0-none to 3-severe), Cornea transparency (from 0-completely transparent to 4-complete cornea opacity), Cornea neovascularization (0-absence of neovascularization to 4-neovascularization between 270° and 360°). The higher the score the worse the outcome. There was not a total score. Please note: ophthalmological evaluations were performed for both eyes. Hence both eyes - right and left - were "study-eyes".

Outcome measures

SECONDARY outcome

Timeframe: Visit 3 - Day 7±1, Visit 4 - Day 14±1 and Visit 5/Final visit/Follow up - Day 21±1

The intraocular pressure (IOP) of the eye was determined by the balance between the amount of aqueous humor that the eye marked and the ease with which it leaved the eye. IOP was performed using Goldmann applanation tonometry after the instillation of a topical anaesthetic. The Goldmann applanation tonometer measured the force necessary to flatten a corneal area of 3.06 mm diameter. At this diameter, the resistance of the cornea to flattening was counterbalanced by the capillary attraction of the tear film meniscus for the tonometer head. The IOP (in mm Hg) equals the flattening force (in grams) multiplied by 10. IOP was measured in both eyes after completion of all other SLEs to avoid potential interference with the other evaluations. Both eyes were tested. Normal eye pressure was between 10 to 21 mm Hg. High intraocular pressure was greater than 21 mm Hg. Please note: ophthalmological evaluations were performed for both eyes. Hence both eyes - right and left - were "study-eyes".

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in IOP (Intraocular Pressure) Left eye - Day 7±1	-0.5 mmHg Standard Deviation 1.6	0.7 mmHg Standard Deviation 1.9
Change From Baseline in IOP (Intraocular Pressure) Right eye - Day 7±1	-0.3 mmHg Standard Deviation 1.8	0.2 mmHg Standard Deviation 1.7
Change From Baseline in IOP (Intraocular Pressure) Left eye - Day 14±1	-0.1 mmHg Standard Deviation 2.5	0.2 mmHg Standard Deviation 2.1
Change From Baseline in IOP (Intraocular Pressure) RIght eye - Day 14±1	0.6 mmHg Standard Deviation 2.1	-0.2 mmHg Standard Deviation 2.0
Change From Baseline in IOP (Intraocular Pressure) Left eye - Day 21±1	-0.3 mmHg Standard Deviation 1.7	0.5 mmHg Standard Deviation 2.0
Change From Baseline in IOP (Intraocular Pressure) Right eye - Day 21±1	-0.3 mmHg Standard Deviation 2.5	0.2 mmHg Standard Deviation 2.6

SECONDARY outcome

Timeframe: from Visit 3 - Day 7±1 to Visit 4 - Day 14±1

Population: The Full Analysis Set (FAS) population included all enrolled subjects, who received at least one dose of the IMD (Lubricin or Vismed®) during the treatment phase.

The number of daily instillations of test and comparator IMD from from Visit 3 - Day 7±1 to Visit 4 - Day 14±1

Outcome measures

Outcome measures
Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Number of Instillations of IMD During the Second Week of the Clinical Investigation Day 7	4.7 number of daily administrations Standard Error 1.1	5.5 number of daily administrations Standard Error 1.0
Number of Instillations of IMD During the Second Week of the Clinical Investigation Day 8	3.7 number of daily administrations Standard Error 1.5	5.1 number of daily administrations Standard Error 1.0
Number of Instillations of IMD During the Second Week of the Clinical Investigation Day 9	3.9 number of daily administrations Standard Error 1.3	4.2 number of daily administrations Standard Error 1.1
Number of Instillations of IMD During the Second Week of the Clinical Investigation Day 10	3.7 number of daily administrations Standard Error 1.1	4.3 number of daily administrations Standard Error 1.0
Number of Instillations of IMD During the Second Week of the Clinical Investigation Day 11	3.7 number of daily administrations Standard Error 1.0	4.4 number of daily administrations Standard Error 1.2
Number of Instillations of IMD During the Second Week of the Clinical Investigation Day 12	3.4 number of daily administrations Standard Error 1.1	4.3 number of daily administrations Standard Error 1.1
Number of Instillations of IMD During the Second Week of the Clinical Investigation Day 13	3.7 number of daily administrations Standard Error 1.2	4.5 number of daily administrations Standard Error 0.9
Number of Instillations of IMD During the Second Week of the Clinical Investigation Day 14	3.7 number of daily administrations Standard Error 1.3	4.2 number of daily administrations Standard Error 1.1

Adverse Events

Lubricin 150 μg/ml (SAF)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Sodium Hyaluronate 0.18% (SAF)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lubricin 150 μg/ml (SAF) n=20 participants at risk Lubricin 150 μg/ml eye drops solution Both test and comparator were instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (SAF) n=20 participants at risk Vismed®, 0.18% sodium hyaluronate eye drops Both test and comparator were instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Musculoskeletal and connective tissue disorders Neck pain	5.0% 1/20 • Number of events 1 • The specific period of time over which adverse events data were collected was from day 1 to day 21±1 An Adverse Event (AE) was defined as any untoward medical occurence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.	5.0% 1/20 • Number of events 1 • The specific period of time over which adverse events data were collected was from day 1 to day 21±1 An Adverse Event (AE) was defined as any untoward medical occurence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Nervous system disorders Headache	10.0% 2/20 • Number of events 2 • The specific period of time over which adverse events data were collected was from day 1 to day 21±1 An Adverse Event (AE) was defined as any untoward medical occurence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.	5.0% 1/20 • Number of events 1 • The specific period of time over which adverse events data were collected was from day 1 to day 21±1 An Adverse Event (AE) was defined as any untoward medical occurence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Additional Information

Clinical Development & Operations

Dompé farmaceutici SpA

Phone: +39 02 583831

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Lubricin 150 μg/ml (FAS) n=19 Participants Lubricin 150 μg/ml eye drops solution The test investigational device as well as the comparator, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Lubricin: Lubricin 150 µg/ml eye drops	Sodium Hyaluronate 0.18% (FAS) n=20 Participants Vismed®, 0.18% sodium hyaluronate eye drops The comparator, as well as the test investigational device, was instilled b.i.d. (two times a day), one drop into each eye, from day 1 to day 7±1 and, then, from 2 to 6 times a day as needed (i.e. prn), one drop into each eye, from day 7±1 to day 14±1. After the end of the treatment period, all the subjects used Vismed® 0.18% b.i.d. every 8±1 h, one drop into each eye, from day 14±1 to day 21±1. Before the start of the treatment (from day -6/-4 to day -1), the subjects were allowed to use only Nebul®, NaCl 0.9% ocular solution q.i.d. every 4±1 h, one drop into each eye. Sodium Hyaluronate: Sodium hyaluronate 0.18% eye drops
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Erythema (Left eye) - Day 14±1	-0.9 score on a scale Standard Deviation 0.9	-0.2 score on a scale Standard Deviation 0.4
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Erythema (Right eye) - Day 14±1	-0.7 score on a scale Standard Deviation 0.9	-0.3 score on a scale Standard Deviation 0.4
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Oedema (Left eye) -Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Oedema (Right eye) -Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lens (Left eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lens (Right eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Iris (Left eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Iris (Right eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Anterior chamber inflammation (Left eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Anterior chamber inflammation (Right eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea transparency (Left eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea transparency (Right eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea neovascularization (Left eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea neovascularization (Right eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Meibomian glands (Left eye) - Day 21±1	-0.2 score on a scale Standard Deviation 0.4	-0.1 score on a scale Standard Deviation 0.4
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Meibomian glands (Right eye) - Day 21±1	-0.2 score on a scale Standard Deviation 0.4	0.0 score on a scale Standard Deviation 0.3
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Erythema (Left eye) - Day 21±1	-0.8 score on a scale Standard Deviation 0.7	-0.2 score on a scale Standard Deviation 0.6
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Erythema (Right eye) - Day 21±1	-0.6 score on a scale Standard Deviation 0.6	-0.1 score on a scale Standard Deviation 0.7
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Oedema (Left eye) - Day 21±1	-0.1 score on a scale Standard Deviation 0.3	-0.1 score on a scale Standard Deviation 0.2
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Oedema ( Right eye) - Day 21±1	-0.1 score on a scale Standard Deviation 0.3	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lashes (Left eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lashes (Right eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Erythema (Left eye) - Day 21±1	-0.9 score on a scale Standard Deviation 0.9	-0.1 score on a scale Standard Deviation 0.6
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Erythema (Right eye) - Day 21±1	-0.8 score on a scale Standard Deviation 0.7	-0.2 score on a scale Standard Deviation 0.7
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Oedema (Left eye) -Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Oedema (Right eye) -Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lens (Left eye) - Day 21±1	-0.1 score on a scale Standard Deviation 0.3	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lens (Right eye) - Day 21±1	-0.1 score on a scale Standard Deviation 0.3	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Iris (Left eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Iris (Right eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Anterior chamber inflammation (Left eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Anterior chamber inflammation (Right eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea transparency (Left eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea transparency (Right eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea neovascularization (Left eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea neovascularization (Right eye) - Day 21±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Meibomian glands (Left eye) - Day 7±1	-0.1 score on a scale Standard Deviation 0.3	-0.1 score on a scale Standard Deviation 0.3
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Meibomian glands (Right eye) - Day 7±1	-0.2 score on a scale Standard Deviation 0.4	-0.1 score on a scale Standard Deviation 0.2
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Erythema (Left eye) - Day 7±1	-0.4 score on a scale Standard Deviation 0.5	-0.2 score on a scale Standard Deviation 0.4
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Erythema (Right eye) - Day 7±1	-0.3 score on a scale Standard Deviation 0.5	-0.1 score on a scale Standard Deviation 0.2
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Oedema (Left eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	-0.1 score on a scale Standard Deviation 0.2
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Oedema (Right eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lashes (Left eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lashes (Right eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Erythema (Left eye) - Day 7±1	-0.4 score on a scale Standard Deviation 0.7	-0.2 score on a scale Standard Deviation 0.4
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Erythema (Right eye) - Day 7±1	-0.4 score on a scale Standard Deviation 0.6	-0.3 score on a scale Standard Deviation 0.4
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Oedema (Left eye) -Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Conjunctiva - Oedema (Right eye) -Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lens (Right eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lens (Left eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Iris (Left eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Iris (Right eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Anterior chamber inflammation (Left eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Anterior chamber inflammation (Right eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea transparency (Left eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea transparency (Right eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea neovascularization (Left eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Cornea neovascularization (Right eye) - Day 7±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Meibomian glands (Left eye) - Day14±1	-0.1 score on a scale Standard Deviation 0.3	-0.2 score on a scale Standard Deviation 0.4
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Meibomian glands (Right eye) - Day14±1	-0.2 score on a scale Standard Deviation 0.4	-0.1 score on a scale Standard Deviation 0.4
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Erythema (Left eye) - Day14±1	-0.6 score on a scale Standard Deviation 0.5	-0.2 score on a scale Standard Deviation 0.4
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Erythema (Right eye) - Day14±1	-0.5 score on a scale Standard Deviation 0.5	-0.1 score on a scale Standard Deviation 0.3
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Oedema (Left eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	-0.1 score on a scale Standard Deviation 0.2
Change From Baseline in Slit Lamp Examination (SLE) Eyelid - Oedema (Right eye) - Day 14±1	-0.1 score on a scale Standard Deviation 0.3	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lashes (Left eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Change From Baseline in Slit Lamp Examination (SLE) Lashes (Right eye) - Day 14±1	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0