Trial Outcomes & Findings for Safety and Efficacy of KPI-121 in Subjects With Dry Eye Disease (NCT NCT02813265)

Last Updated: 2021-02-03

Results Overview

Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

918 participants

Primary outcome timeframe

Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Results posted on

2021-02-03

Participant Flow

918 subjects were randomized, 3 of which were not included in any analysis population as they had participated in more than one study. The data for the second-participation for these 3 individuals were not included in any analysis population as agreed upon with the FDA.

Participant milestones

Participant milestones
Measure	KPI-121 0.25% Ophthalmic Suspension Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Overall Study STARTED	459	456
Overall Study COMPLETED	455	453
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of KPI-121 in Subjects With Dry Eye Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KPI-121 0.25% Ophthalmic Suspension n=459 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=456 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension	Total n=915 Participants Total of all reporting groups
Age, Continuous	58.1 Years STANDARD_DEVIATION 15.41 • n=5 Participants	58.3 Years STANDARD_DEVIATION 14.66 • n=7 Participants	58.2 Years STANDARD_DEVIATION 15.03 • n=5 Participants
Sex: Female, Male Female	367 Participants n=5 Participants	359 Participants n=7 Participants	726 Participants n=5 Participants
Sex: Female, Male Male	92 Participants n=5 Participants	97 Participants n=7 Participants	189 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	69 Participants n=5 Participants	71 Participants n=7 Participants	140 Participants n=5 Participants
Race (NIH/OMB) White	362 Participants n=5 Participants	361 Participants n=7 Participants	723 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment United States	459 participants n=5 Participants	456 participants n=7 Participants	915 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=452 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=451 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15)	-0.4049 score on a scale Standard Deviation 0.65062	-0.1574 score on a scale Standard Deviation 0.60704

PRIMARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed

Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=455 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=452 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15)	-14.53 score on a scale Standard Deviation 20.636	-9.16 score on a scale Standard Deviation 17.924

PRIMARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed

Comparison of mean corneal fluorescein staining between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=455 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=452 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Corneal Fluorescein Staining Score at Visit 4 (Day 15)	-0.5 score on a scale Standard Deviation 0.84	-0.4 score on a scale Standard Deviation 0.79

PRIMARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Population: Sub-group of Intent to Treat population with more severe ocular discomfort minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=233 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=238 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) Ocular Discomfort Severity at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort	-16.67 score on a scale Standard Deviation 21.937	-10.76 score on a scale Standard Deviation 18.037

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=256 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=264 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change in Conjunctival Hyperemia Scores at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort at Baseline (Day 1)	-0.4648 score on a scale Standard Deviation 0.66770	-0.2045 score on a scale Standard Deviation 0.62567

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Proportion of subjects with ≥1 improvement from baseline in conjunctival hyperemia scores. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=452 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=451 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Proportion of Subjects With ≥1 Improvement in Conjunctival Hyperemia at Visit 4 (Day 15)	189 Participants	98 Participants

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=453 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=450 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) Conjunctival Hyperemia Scores at Visit 4 (Day 15) for the Mean of All Regions (Nasal, Temporal, Frontal)	-0.2980 score on a scale Standard Deviation 0.59018	-0.0421 score on a scale Standard Deviation 0.51921

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)

Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=457 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=455 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change in Ocular Discomfort Severity Scores Prior to Visit 3 (Day 8) Minus the Mean of the Scores to Baseline/Visit 2 (Day 1)	-8.12 score on a scale Standard Deviation 16.880	-4.81 score on a scale Standard Deviation 14.851

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=258 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=263 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change in Ocular Discomfort Severity Scores Prior to Visit 3 (Day 8) Minus Baseline/Visit 2 (Day 1) in the Subgroup of Participants With More Severe Ocular Discomfort.	-9.90 score on a scale Standard Deviation 17.835	-6.38 score on a scale Standard Deviation 15.289

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)

Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=455 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=452 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change in Ocular Discomfort Severity Scores on Day 4 (Diary) Minus Baseline/Visit 2 (Day 1)	-6.60 score on a scale Standard Deviation 16.710	-3.20 score on a scale Standard Deviation 15.125

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8)

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=256 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=261 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change in Ocular Discomfort Severity Scores on Day 4 Day 4 (Diary) Minus Baseline/Visit 2 (Day 1) in the Subgroup of Participants With More Severe Ocular Discomfort	-8.48 score on a scale Standard Deviation 17.412	-5.20 score on a scale Standard Deviation 14.903

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)

Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale in a sub-group of participants with more severe ocular discomfort at baseline.. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=379 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=379 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Conjunctival Hyperemia Scores With a Day 1 Conjunctival Hyperemia Score of ≥ 2 in the Subgroup of Participants With More Severe Ocular Discomfort	-0.47 score on a scale Standard Deviation 0.631	-0.22 score on a scale Standard Deviation 0.577

SECONDARY outcome

Timeframe: Visit 4 (Day 15)

Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=453 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=451 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Subjects With a Grade of 0 in Conjunctival Hyperemia Score at Visit 4 (Day 15)	27 Participants	16 Participants

Adverse Events

KPI-121 0.25% Ophthalmic Suspension

Serious events: 0 serious events

Other events: 66 other events

Deaths: 0 deaths

Vehicle of KPI-121 0.25% Ophthalmic Suspension

Serious events: 0 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

VP, Clinical Development

Kala Pharmaceuticals, Inc

Phone: (781) 996-5252

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The agreement between the Principal Investigator and the Sponsor restricts the PI's rights to discuss or publish trial results until after the first to occur of the following: (a) publication of such multi-center clinical trial results; (b) notification by sponsor that such a multi-center clinical trial submission is no longer planned; or ( c) the eighteen ( 18) month anniversary of the completion, abandonment or termination of such multi-center clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	KPI-121 0.25% Ophthalmic Suspension n=459 participants at risk Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=456 participants at risk Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
General disorders Instillation site foreign body sensation	0.44% 2/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
General disorders Instillation site lacrimation	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
General disorders Instillation site pruritus	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.66% 3/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
General disorders Installation site discomfort	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
General disorders Installation site reaction	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Immune system disorders Hypersensitivity	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Infections and infestations Pneumonia	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Infections and infestations Sinusitis	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Infections and infestations Upper respiratory tract infection	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.44% 2/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Infections and infestations Bronchitis	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Infections and infestations Conjunctivitis	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Infections and infestations Herpes zoster	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Infections and infestations Nasopharyngitis	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.66% 3/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Infections and infestations Urinary tract infection	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Injury, poisoning and procedural complications Arthropod bite	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Injury, poisoning and procedural complications Ligament Sprain	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Injury, poisoning and procedural complications Fall	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Investigations Intraocular pressure increased	0.65% 3/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Musculoskeletal and connective tissue disorders Spinal Column Stenosis	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Nervous system disorders Headache	0.44% 2/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Nervous system disorders Hypoaesthesia	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Nervous system disorders Nerve Compression	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Nervous system disorders Sinus Headache	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Psychiatric disorders Anxiety	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Skin and subcutaneous tissue disorders Dermatitis Contact	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Skin and subcutaneous tissue disorders Eccymosis	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Skin and subcutaneous tissue disorders Rash	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Ocular hyperaemia	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Photophobia	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Punctate keratitis	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Conjunctival vascular disorder	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Eye discharge	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Eye Pruritus	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.88% 4/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Eyelid margin crusting	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.44% 2/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Eyelid ptosis	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Trichiasis	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Vision Blurred	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.44% 2/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Vitreous detachment	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Blepharospasm	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Gastrointestinal disorders hypoaesthesia oral	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Gastrointestinal disorders Toothache	0.22% 1/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Gastrointestinal disorders Gingival bleeding	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
General disorders Installation site pain	6.1% 28/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	6.1% 28/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Keratitis	0.00% 0/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Eye Irritation	1.1% 5/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	1.5% 7/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Blepharitis	0.65% 3/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.00% 0/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Lacrimination increased	0.65% 3/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.44% 2/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Conjunctival hyperemia	0.44% 2/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.88% 4/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Eye Pain	0.44% 2/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.22% 1/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).
Eye disorders Foreign Body Sensation	0.44% 2/459 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).	0.88% 4/456 • Adverse events were collected at Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15).