Trial Outcomes & Findings for Double-masked Study of AR-13324 Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension (NCT NCT02207491)
NCT ID: NCT02207491
Last Updated: 2018-04-13
Results Overview
The primary efficacy outcome is mean IOP
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
411 participants
Primary outcome timeframe
3 months
Results posted on
2018-04-13
Participant Flow
Participants were recruited at 35 clinical trial sites starting in June of 2014. The first participant was enrolled in July of 2014 and the last participant was enrolled in December of 2014.
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. The Randomized Population includes all subjects who were randomized to treatment. Baseline variables and demographic characteristics were summarized for this population.
Participant milestones
| Measure |
AR-13324 Ophthalmic Solution 0.02% & Placebo
1 drop AR-13324 in the evening (PM) \& 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)
|
|---|---|---|
|
Overall Study
STARTED
|
202
|
209
|
|
Overall Study
COMPLETED
|
171
|
196
|
|
Overall Study
NOT COMPLETED
|
31
|
13
|
Reasons for withdrawal
| Measure |
AR-13324 Ophthalmic Solution 0.02% & Placebo
1 drop AR-13324 in the evening (PM) \& 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)
|
|---|---|---|
|
Overall Study
Adverse Event
|
20
|
4
|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Non-compliant
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
3
|
0
|
|
Overall Study
Physician Decision
|
2
|
0
|
|
Overall Study
Protocol Violation
|
3
|
5
|
Baseline Characteristics
Double-masked Study of AR-13324 Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension
Baseline characteristics by cohort
| Measure |
AR-13324 Ophthalmic Solution 0.02% & Placebo
n=202 Participants
1 drop AR-13324 in the evening (PM) \& 1 drop placebo in the morning (AM) in both eyes (OU)
|
Timolol Maleate Ophthalmic Solution 0.5% BID
n=209 Participants
1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
|
Total
n=411 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.8 years
STANDARD_DEVIATION 11.65 • n=5 Participants
|
64.2 years
STANDARD_DEVIATION 11.34 • n=7 Participants
|
65.0 years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
114 Participants
n=5 Participants
|
136 Participants
n=7 Participants
|
250 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
88 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
161 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
27 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
175 Participants
n=5 Participants
|
181 Participants
n=7 Participants
|
356 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 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
|
43 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
157 Participants
n=5 Participants
|
153 Participants
n=7 Participants
|
310 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
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: Per-Protocol (PP) Population. The PP population includes subjects who did not have major protocol violations likely to seriously affect the primary outcome of the study. The PP population summarizes subjects as treated for purpose of analysis.
The primary efficacy outcome is mean IOP
Outcome measures
| Measure |
AR-13324 Ophthalmic Solution 0.02% & Placebo
n=182 Participants
1 drop AR-13324 in the evening (PM) \& 1 drop placebo in the morning (AM) in both eyes (OU)
|
Timolol Maleate Ophthalmic Solution 0.5% BID
n=188 Participants
1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
|
|---|---|---|
|
Intraocular Pressure (IOP)
Day 1, 0800 hours
|
23.42 mmHg
Standard Deviation 1.756
|
23.37 mmHg
Standard Deviation 1.658
|
|
Intraocular Pressure (IOP)
Day 1, 1000 hours
|
22.28 mmHg
Standard Deviation 2.128
|
21.92 mmHg
Standard Deviation 2.053
|
|
Intraocular Pressure (IOP)
Day 1, 1600 hours
|
21.78 mmHg
Standard Deviation 2.385
|
21.45 mmHg
Standard Deviation 2.365
|
|
Intraocular Pressure (IOP)
Day 15, 0800 hours
|
18.68 mmHg
Standard Deviation 3.342
|
18.33 mmHg
Standard Deviation 2.566
|
|
Intraocular Pressure (IOP)
Day 15, 1000 hours
|
17.29 mmHg
Standard Deviation 3.303
|
17.55 mmHg
Standard Deviation 2.570
|
|
Intraocular Pressure (IOP)
Day 15, 1600 hours
|
17.24 mmHg
Standard Deviation 3.294
|
17.70 mmHg
Standard Deviation 2.661
|
|
Intraocular Pressure (IOP)
Day 43, 0800 hours
|
19.35 mmHg
Standard Deviation 3.629
|
18.24 mmHg
Standard Deviation 2.924
|
|
Intraocular Pressure (IOP)
Day 43, 1000 hours
|
18.14 mmHg
Standard Deviation 3.502
|
17.44 mmHg
Standard Deviation 2.725
|
|
Intraocular Pressure (IOP)
Day 43, 1600 hours
|
17.86 mmHg
Standard Deviation 3.580
|
17.71 mmHg
Standard Deviation 2.820
|
|
Intraocular Pressure (IOP)
Day 90 (month 3), 0800 hours
|
19.81 mmHg
Standard Deviation 3.647
|
18.47 mmHg
Standard Deviation 2.711
|
|
Intraocular Pressure (IOP)
Day 90 (month 3), 1000 hours
|
18.92 mmHg
Standard Deviation 3.702
|
17.96 mmHg
Standard Deviation 2.674
|
|
Intraocular Pressure (IOP)
Day 90 (month 3), 1600 hours
|
18.48 mmHg
Standard Deviation 3.595
|
17.74 mmHg
Standard Deviation 2.546
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: Safety Population: all randomized subjects who received at least 1 dose of study medication. The safety population summarizes subjects as treated for purpose of analysis. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
Exposure to study medication in days for all treatment groups.
Outcome measures
| Measure |
AR-13324 Ophthalmic Solution 0.02% & Placebo
n=203 Participants
1 drop AR-13324 in the evening (PM) \& 1 drop placebo in the morning (AM) in both eyes (OU)
|
Timolol Maleate Ophthalmic Solution 0.5% BID
n=208 Participants
1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
|
|---|---|---|
|
Extent of Exposure
|
82.8 days
Standard Deviation 21.44
|
87.4 days
Standard Deviation 15.53
|
Adverse Events
AR-13324 Ophthalmic Solution 0.02% & Placebo
Serious events: 3 serious events
Other events: 145 other events
Deaths: 0 deaths
Timolol Maleate Ophthalmic Solution 0.5% BID
Serious events: 4 serious events
Other events: 75 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AR-13324 Ophthalmic Solution 0.02% & Placebo
n=203 participants at risk
1 drop AR-13324 in the evening (PM) \& 1 drop placebo in the morning (AM) in both eyes (OU)
|
Timolol Maleate Ophthalmic Solution 0.5% BID
n=208 participants at risk
1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
|
|---|---|---|
|
Reproductive system and breast disorders
Worsening of Adenomyosis
|
0.00%
0/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.48%
1/208 • Number of events 1 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Cardiac disorders
Congestive Heart Failure
|
0.00%
0/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.48%
1/208 • Number of events 1 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Nervous system disorders
Left Upper Extremity Numbness
|
0.00%
0/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.48%
1/208 • Number of events 1 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Nervous system disorders
Stroke (CVA)
|
0.00%
0/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.48%
1/208 • Number of events 1 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer
|
0.49%
1/203 • Number of events 1 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.00%
0/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Cardiac disorders
Exacerbation of Coronary Artery Disease
|
0.49%
1/203 • Number of events 1 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.00%
0/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Vascular disorders
Hypertension
|
0.49%
1/203 • Number of events 1 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.00%
0/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.48%
1/208 • Number of events 1 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.00%
0/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.48%
1/208 • Number of events 1 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
Other adverse events
| Measure |
AR-13324 Ophthalmic Solution 0.02% & Placebo
n=203 participants at risk
1 drop AR-13324 in the evening (PM) \& 1 drop placebo in the morning (AM) in both eyes (OU)
|
Timolol Maleate Ophthalmic Solution 0.5% BID
n=208 participants at risk
1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
|
|---|---|---|
|
Eye disorders
Conjunctival hyperemia
|
53.2%
108/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
8.2%
17/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Eye disorders
Conjunctival Haemmorrhage
|
15.8%
32/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.96%
2/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Eye disorders
Cornea Verticillata
|
5.9%
12/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.00%
0/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Eye disorders
Erythema of Eyelid
|
5.9%
12/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.00%
0/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Eye disorders
Vision Blurred
|
5.4%
11/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
0.48%
1/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
General disorders
Instillation Site Pain
|
14.8%
30/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
20.2%
42/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
General disorders
Instillation Site Erythema
|
11.8%
24/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
1.9%
4/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
|
Investigations
Vital Dye Staining Cornea Present
|
8.4%
17/203 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
9.1%
19/208 • Adverse event data was collected during the course of the 90-day treatment period.
The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. Three (3) subjects received incorrect study medication from that to which they were randomized, shown in the Participant Flow.
|
Additional Information
Nancy Ramirez-Davis, Director 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