Trial Outcomes & Findings for Evaluation of Netarsudil (AR-13324) Ophthalmic Solution in Patients With Glaucoma and Ocular Hypertension (NCT NCT02207621)

NCT ID: NCT02207621

Last Updated: 2018-04-06

Results Overview

The primary efficacy outcome is mean intraocular pressure (IOP)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

756 participants

Primary outcome timeframe

3 months

Results posted on

2018-04-06

Participant Flow

62 clinical trial sites participated in this study, of which 60 clinical trial sites enrolled participants. Screening started in June 2014. Enrollment started in July 2014. The last participant was enrolled in March 2015.

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

Participant milestones

Participant milestones
Measure	AR-13324 Ophthalmic Solution 0.02% & Placebo 1 drop AR-13324 in the evening (PM) and 1 drop placebo in the morning (AM) in both eyes (OU)	Timolol Maleate Ophthalmic Solution 0.5% BID 1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)	AR-13324 Ophthalmic Solution 0.02% BID 1 drop AR-13324 twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
Overall Study STARTED	251	251	254
Overall Study COMPLETED	146	204	86
Overall Study NOT COMPLETED	105	47	168

Reasons for withdrawal

Reasons for withdrawal
Measure	AR-13324 Ophthalmic Solution 0.02% & Placebo 1 drop AR-13324 in the evening (PM) and 1 drop placebo in the morning (AM) in both eyes (OU)	Timolol Maleate Ophthalmic Solution 0.5% BID 1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)	AR-13324 Ophthalmic Solution 0.02% BID 1 drop AR-13324 twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
Overall Study Adverse Event	71	15	132
Overall Study Withdrawal by Subject	9	9	13
Overall Study Non-Compliant	3	3	1
Overall Study Lost to Follow-up	1	0	3
Overall Study Lack of Efficacy	10	2	4
Overall Study Disallowed Concurrent Medication	2	5	2
Overall Study Physician Decision	1	2	2
Overall Study Protocol Violation	4	10	6
Overall Study Death	2	0	0
Overall Study Other(Site,Sponsor and Subject request)	2	1	5

Baseline Characteristics

Evaluation of Netarsudil (AR-13324) Ophthalmic Solution in Patients With Glaucoma and Ocular Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AR-13324 Ophthalmic Solution 0.02% & Placebo n=251 Participants 1 drop AR-13324 in the evening (PM) and 1 drop placebo in the morning (AM) in both eyes (OU)	Timolol Maleate Ophthalmic Solution 0.5% BID n=251 Participants 1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)	AR-13324 Ophthalmic Solution 0.02% BID n=254 Participants 1 drop AR-13324 twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)	Total n=756 Participants Total of all reporting groups
Age, Continuous	65.3 Years STANDARD_DEVIATION 11.48 • n=5 Participants	63 Years STANDARD_DEVIATION 11.81 • n=7 Participants	64.1 Years STANDARD_DEVIATION 12.46 • n=5 Participants	64.1 Years STANDARD_DEVIATION 11.95 • n=4 Participants
Sex: Female, Male Female	148 Participants n=5 Participants	150 Participants n=7 Participants	165 Participants n=5 Participants	463 Participants n=4 Participants
Sex: Female, Male Male	103 Participants n=5 Participants	101 Participants n=7 Participants	89 Participants n=5 Participants	293 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	41 Participants n=5 Participants	42 Participants n=7 Participants	43 Participants n=5 Participants	126 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	210 Participants n=5 Participants	209 Participants n=7 Participants	211 Participants n=5 Participants	630 Participants n=4 Participants
Ethnicity (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
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 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
Race (NIH/OMB) Black or African American	69 Participants n=5 Participants	76 Participants n=7 Participants	69 Participants n=5 Participants	214 Participants n=4 Participants
Race (NIH/OMB) White	178 Participants n=5 Participants	166 Participants n=7 Participants	177 Participants n=5 Participants	521 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: 3 months

Population: The Per Protocol (PP) population includes all subjects who did not have a major protocol violation likely to seriously affect the primary outcome of the study. This is the primary population for efficacy analyses.

The primary efficacy outcome is mean intraocular pressure (IOP)

Outcome measures

Outcome measures
Measure	AR-13324 Ophthalmic Solution 0.02% & Placebo n=206 Participants 1 drop AR-13324 in the PM \& 1 drop placebo in the AM, OU	Timolol Maleate Ophthalmic Solution 0.5% BID n=217 Participants 1 drop Timolol maleate BID in the AM and PM, OU	AR-13324 Ophthalmic Solution 0.02% BID n=209 Participants 1 drop AR-13324 BID in the AM and PM, OU
Intraocular Pressure (IOP) Day 1, 0800 hours	23.51 mmHg Standard Deviation 1.654	23.45 mmHg Standard Deviation 1.601	23.50 mmHg Standard Deviation 1.671
Intraocular Pressure (IOP) Day 1, 1000 hours	22.31 mmHg Standard Deviation 2.131	22.18 mmHg Standard Deviation 2.089	22.26 mmHg Standard Deviation 2.103
Intraocular Pressure (IOP) Day 1, 1600 hours	21.56 mmHg Standard Deviation 2.338	21.61 mmHg Standard Deviation 2.369	21.49 mmHg Standard Deviation 2.279
Intraocular Pressure (IOP) Day 15, 0800 hours	19.01 mmHg Standard Deviation 2.979	18.25 mmHg Standard Deviation 2.736	18.20 mmHg Standard Deviation 3.491
Intraocular Pressure (IOP) Day 15, 1000 hours	17.74 mmHg Standard Deviation 3.089	17.49 mmHg Standard Deviation 2.796	16.91 mmHg Standard Deviation 3.087
Intraocular Pressure (IOP) Day 15, 1600 hours	17.37 mmHg Standard Deviation 2.830	17.59 mmHg Standard Deviation 2.935	16.28 mmHg Standard Deviation 2.925
Intraocular Pressure (IOP) Day 43, 0800 hours	19.37 mmHg Standard Deviation 3.749	18.08 mmHg Standard Deviation 2.614	18.57 mmHg Standard Deviation 3.206
Intraocular Pressure (IOP) Day 43, 1000 hours	18.10 mmHg Standard Deviation 3.335	17.31 mmHg Standard Deviation 2.805	17.09 mmHg Standard Deviation 3.028
Intraocular Pressure (IOP) Day 43, 1600 hours	17.88 mmHg Standard Deviation 2.888	17.25 mmHg Standard Deviation 2.813	16.58 mmHg Standard Deviation 3.095
Intraocular Pressure (IOP) Day 90 (Month 3), 0800 hours	19.43 mmHg Standard Deviation 3.761	18.21 mmHg Standard Deviation 2.819	18.66 mmHg Standard Deviation 3.460
Intraocular Pressure (IOP) Day 90 (Month 3), 1000 hours	18.18 mmHg Standard Deviation 3.571	17.52 mmHg Standard Deviation 2.777	17.81 mmHg Standard Deviation 3.330
Intraocular Pressure (IOP) Day 90 (Month 3), 1600 hours	17.73 mmHg Standard Deviation 3.386	17.67 mmHg Standard Deviation 2.879	17.08 mmHg Standard Deviation 3.112

SECONDARY outcome

Timeframe: 12 Months

Population: The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. The safety population summarized subjects as treated for purpose of analysis. One (1) subject did not receive study drug as randomized, shown in the Participant Flow

Exposure to study medication in days for all treatment groups

Outcome measures

Outcome measures
Measure	AR-13324 Ophthalmic Solution 0.02% & Placebo n=251 Participants 1 drop AR-13324 in the PM \& 1 drop placebo in the AM, OU	Timolol Maleate Ophthalmic Solution 0.5% BID n=251 Participants 1 drop Timolol maleate BID in the AM and PM, OU	AR-13324 Ophthalmic Solution 0.02% BID n=253 Participants 1 drop AR-13324 BID in the AM and PM, OU
Extent of Exposure	259.7 days Standard Deviation 133.34	324.5 days Standard Deviation 90.73	185.2 days Standard Deviation 144.56

Adverse Events

AR-13324 Ophthalmic Solution 0.02% & Placebo

Serious events: 17 serious events

Other events: 198 other events

Deaths: 2 deaths

Timolol Maleate Ophthalmic Solution 0.5% BID

Serious events: 12 serious events

Other events: 96 other events

Deaths: 0 deaths

AR-13324 Ophthalmic Solution 0.02% BID

Serious events: 7 serious events

Other events: 213 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	AR-13324 Ophthalmic Solution 0.02% & Placebo n=251 participants at risk 1 drop AR-13324 in the PM and 1 drop placebo in the AM, OU	Timolol Maleate Ophthalmic Solution 0.5% BID n=251 participants at risk 1 drop Timolol maleate BID in the AM and PM, OU	AR-13324 Ophthalmic Solution 0.02% BID n=253 participants at risk 1 drop AR-13324 BID in the AM and PM, OU
General disorders Instillation Site Erythema	5.6% 14/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	2.0% 5/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	12.6% 32/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Investigations Vital Dye Staining Cornea Present	5.6% 14/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	5.6% 14/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	6.7% 17/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Conjunctival Hyperaemia	60.6% 152/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	13.9% 35/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	66.4% 168/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Cornea Verticillata	25.5% 64/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	0.80% 2/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	25.3% 64/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Conjunctival Haemorrhage	19.5% 49/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	0.80% 2/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	19.4% 49/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Vision Blurred	10.8% 27/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	2.8% 7/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	17.4% 44/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Lacrimation Increased	7.6% 19/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	0.00% 0/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	9.9% 25/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Visual Acuity Reduced	8.8% 22/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	2.4% 6/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	8.7% 22/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Eye Pruritus	5.6% 14/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	1.2% 3/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	7.9% 20/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Conjunctival Oedema	3.2% 8/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	0.00% 0/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	7.5% 19/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Erythema of Eyelid	5.6% 14/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	0.80% 2/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	4.7% 12/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Eye Irritation	4.4% 11/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	3.2% 8/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	5.1% 13/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
Eye disorders Foreign Body Sensation in Eyes	2.8% 7/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	0.40% 1/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	5.5% 14/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.
General disorders Instillation Site Pain	17.9% 45/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	16.3% 41/251 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.	17.8% 45/253 • 1 year The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.

Additional Information

Nancy Ramirez-Davis, Director of Clinical Project Management

Aerie Pharmaceuticals, Inc.

Phone: 908-947-3543

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place