Trial Outcomes & Findings for Efficacy and Systemic Safety of Netarsudil 0.01%, 0.02%, 0.04% Relative to Placebo in Subjects With Open-angle Glaucoma or Ocular Hypertension in Japan (NCT NCT03844945)

NCT ID: NCT03844945

Last Updated: 2020-10-19

Results Overview

Mean diurnal IOP within a treatment by Goldman Applanation Tonometry

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

215 participants

Primary outcome timeframe

29 Days

Results posted on

2020-10-19

Participant Flow

Participants were recruited at 25 clinical trial sites in Japan.

Prior to enrollment, adult participants were to have a Screening Visit and 2 Qualification Visits to allow for washout of ocular hypotensive medication if needed.

Participant milestones

Participant milestones
Measure	Netarsudil Ophthalmic Solution 0.01% 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.01%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.02% 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.02%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.04% 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.04%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution Placebo 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution Placebo: Topical sterile ophthalmic solution
Overall Study STARTED	55	54	51	55
Overall Study COMPLETED	54	53	46	54
Overall Study NOT COMPLETED	1	1	5	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Netarsudil Ophthalmic Solution 0.01% 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.01%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.02% 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.02%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.04% 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.04%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution Placebo 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution Placebo: Topical sterile ophthalmic solution
Overall Study Adverse Event	1	1	4	0
Overall Study Withdrawal by Subject	0	0	1	0
Overall Study Lack of Efficacy	0	0	0	1

Baseline Characteristics

Efficacy and Systemic Safety of Netarsudil 0.01%, 0.02%, 0.04% Relative to Placebo in Subjects With Open-angle Glaucoma or Ocular Hypertension in Japan

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Netarsudil Ophthalmic Solution 0.01% n=55 Participants 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.01%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.02% n=54 Participants 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.02%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.04% n=51 Participants 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.04%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution Placebo n=55 Participants 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution Placebo: Topical sterile ophthalmic solution	Total n=215 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 14.62 • n=5 Participants	64.1 years STANDARD_DEVIATION 12.16 • n=7 Participants	62 years STANDARD_DEVIATION 13.56 • n=5 Participants	64.6 years STANDARD_DEVIATION 12.58 • n=4 Participants	63.35 years STANDARD_DEVIATION 13.23 • n=21 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	29 Participants n=7 Participants	27 Participants n=5 Participants	31 Participants n=4 Participants	123 Participants n=21 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	25 Participants n=7 Participants	24 Participants n=5 Participants	24 Participants n=4 Participants	92 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	55 Participants n=5 Participants	54 Participants n=7 Participants	51 Participants n=5 Participants	55 Participants n=4 Participants	215 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: 29 Days

Population: Intent to treat (ITT) population

Mean diurnal IOP within a treatment by Goldman Applanation Tonometry

Outcome measures

Outcome measures
Measure	Netarsudil Ophthalmic Solution 0.01% n=55 Participants 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.01%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.02% n=54 Participants 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.02%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.04% n=51 Participants 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.04%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution Placebo n=55 Participants 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution Placebo: Topical sterile ophthalmic solution
Intraocular Pressure (IOP) Day 8	16.2 mmHg Standard Deviation 2.568	15.9 mmHg Standard Deviation 2.673	15.7 mmHg Standard Deviation 4.014	19.8 mmHg Standard Deviation 4.059
Intraocular Pressure (IOP) Day 1	20.5 mmHg Standard Deviation 2.8362	20.3 mmHg Standard Deviation 2.8039	20.8 mmHg Standard Deviation 3.2037	21.1 mmHg Standard Deviation 3.7023
Intraocular Pressure (IOP) Day 15	15.9 mmHg Standard Deviation 2.703	15.6 mmHg Standard Deviation 2.573	15.7 mmHg Standard Deviation 4.190	19.3 mmHg Standard Deviation 3.702
Intraocular Pressure (IOP) Day 29	16.3 mmHg Standard Deviation 2.609	15.4 mmHg Standard Deviation 2.411	16.2 mmHg Standard Deviation 4.496	19.3 mmHg Standard Deviation 3.728

Adverse Events

Netarsudil Ophthalmic Solution 0.01%

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Netarsudil Ophthalmic Solution 0.02%

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Netarsudil Ophthalmic Solution 0.04%

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Netarsudil Ophthalmic Solution Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Clinical Research, Japan

Aerie Pharmaceuticals Ireland Limited, Japan Branch

Phone: +81-3-6860-8410

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Prior to publishing any trial results, site shall provide the to be published information to the Sponsor for review and obtain written approval at least thirty (30) days in advance of publication.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Netarsudil Ophthalmic Solution 0.01% n=55 participants at risk 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.01%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.02% n=54 participants at risk 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.02%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution 0.04% n=51 participants at risk 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.04%: Topical sterile ophthalmic solution	Netarsudil Ophthalmic Solution Placebo n=55 participants at risk 1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution Placebo: Topical sterile ophthalmic solution
Eye disorders Abnormal sensation in eye	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Eye pain	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	3.9% 2/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Visual acuity reduced	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Blepharitis	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Chalazion	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Conjunctival follicles	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Corneal erosion	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Dry eye	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Erythema of eyelid	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Iritis	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Keratitis	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Lacrimation increased	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Retinal exudates	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Retinal tear	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Swelling of eyelid	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Trichiasis	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Ulcerative keratitis	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Vernal keratoconjuncitvitis	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Visual acuity reduced transiently	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Infections and infestations Conjunctivitis	3.6% 2/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	3.9% 2/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
General disorders Instillation site foreign body sensation	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Renal and urinary disorders Urine abnormality	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
General disorders Instillation site pain	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Investigations Intraocular pressure increased	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Injury, poisoning and procedural complications Corneal abrasion	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	3.7% 2/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	5.9% 3/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Infections and infestations Cystitis	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Infections and infestations Gastritis bacterial	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Infections and infestations Gastroenteritis	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Infections and infestations Gingivitis	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Gastrointestinal disorders Toothache	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Hepatobiliary disorders Hepatic function abnormal	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Investigations Urine leukocyte esterase positive	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Nervous system disorders Dizziness	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Conjunctival Hyperemia	23.6% 13/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	37.0% 20/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	56.9% 29/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Eye Irritation	5.5% 3/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	9.3% 5/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	3.9% 2/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Conjunctival Hemorrhage	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	5.6% 3/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	5.9% 3/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.
Eye disorders Eye Discharge	1.8% 1/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	1.9% 1/54 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	2.0% 1/51 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.	0.00% 0/55 • Ocular/Systemic safety during a 4-week treatment period Safety population, defined as all randomized subjects who received at least one dose of study drug.