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Trial record 8 of 19 for:    netarsudil

Double-masked Study of AR-13324 Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension (Rocket-1)

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ClinicalTrials.gov Identifier: NCT02207491
Recruitment Status : Completed
First Posted : August 4, 2014
Results First Posted : April 13, 2018
Last Update Posted : April 13, 2018
Sponsor:
Information provided by (Responsible Party):
Aerie Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Ocular Hypertension
Open-angle Glaucoma
Interventions Drug: Timolol maleate Ophthalmic Solution 0.5% BID
Drug: AR-13324 Ophthalmic Solution 0.02%
Other: Placebo
Enrollment 411
Recruitment Details 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.
Pre-assignment Details

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.

Arm/Group Title AR-13324 Ophthalmic Solution 0.02% & Placebo Timolol Maleate Ophthalmic Solution 0.5% BID
Hide Arm/Group Description 1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU) 1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
Period Title: Overall Study
Started 202 209
Completed 171 196
Not Completed 31 13
Reason Not Completed
Adverse Event             20             4
Withdrawal by Subject             3             2
Non-compliant             0             1
Lost to Follow-up             0             1
Lack of Efficacy             3             0
Physician Decision             2             0
Protocol Violation             3             5
Arm/Group Title AR-13324 Ophthalmic Solution 0.02% & Placebo Timolol Maleate Ophthalmic Solution 0.5% BID Total
Hide Arm/Group Description 1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU) 1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU) Total of all reporting groups
Overall Number of Baseline Participants 202 209 411
Hide Baseline Analysis Population Description
Randomized Population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 202 participants 209 participants 411 participants
65.8  (11.65) 64.2  (11.34) 65.0  (11.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 202 participants 209 participants 411 participants
Female
114
  56.4%
136
  65.1%
250
  60.8%
Male
88
  43.6%
73
  34.9%
161
  39.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 202 participants 209 participants 411 participants
Hispanic or Latino
27
  13.4%
28
  13.4%
55
  13.4%
Not Hispanic or Latino
175
  86.6%
181
  86.6%
356
  86.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 202 participants 209 participants 411 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   1.0%
4
   1.9%
6
   1.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
43
  21.3%
51
  24.4%
94
  22.9%
White
157
  77.7%
153
  73.2%
310
  75.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   0.5%
1
   0.2%
1.Primary Outcome
Title Intraocular Pressure (IOP)
Hide Description The primary efficacy outcome is mean IOP
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title AR-13324 Ophthalmic Solution 0.02% & Placebo Timolol Maleate Ophthalmic Solution 0.5% BID
Hide Arm/Group Description:
1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU)
1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
Overall Number of Participants Analyzed 182 188
Mean (Standard Deviation)
Unit of Measure: mmHg
Day 1, 0800 hours Number Analyzed 182 participants 188 participants
23.42  (1.756) 23.37  (1.658)
Day 1, 1000 hours Number Analyzed 182 participants 188 participants
22.28  (2.128) 21.92  (2.053)
Day 1, 1600 hours Number Analyzed 182 participants 188 participants
21.78  (2.385) 21.45  (2.365)
Day 15, 0800 hours Number Analyzed 177 participants 187 participants
18.68  (3.342) 18.33  (2.566)
Day 15, 1000 hours Number Analyzed 176 participants 186 participants
17.29  (3.303) 17.55  (2.570)
Day 15, 1600 hours Number Analyzed 176 participants 186 participants
17.24  (3.294) 17.70  (2.661)
Day 43, 0800 hours Number Analyzed 170 participants 184 participants
19.35  (3.629) 18.24  (2.924)
Day 43, 1000 hours Number Analyzed 170 participants 184 participants
18.14  (3.502) 17.44  (2.725)
Day 43, 1600 hours Number Analyzed 170 participants 183 participants
17.86  (3.580) 17.71  (2.820)
Day 90 (month 3), 0800 hours Number Analyzed 157 participants 181 participants
19.81  (3.647) 18.47  (2.711)
Day 90 (month 3), 1000 hours Number Analyzed 158 participants 181 participants
18.92  (3.702) 17.96  (2.674)
Day 90 (month 3), 1600 hours Number Analyzed 158 participants 181 participants
18.48  (3.595) 17.74  (2.546)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AR-13324 Ophthalmic Solution 0.02% & Placebo, Timolol Maleate Ophthalmic Solution 0.5% BID
Comments Assuming zero difference between AR-13324 and timolol, a 2-tailed alpha of 0.05 at each of 9 time points, a common SD of 3.0 mmHg, and a correlation between time points of 0.60 or less, 170 PP subjects per arm were necessary to have 90% power to show clinical noninferiority of AR-13324 to timolol in mean IOP.
Type of Statistical Test Non-Inferiority
Comments Clinical noninferiority was to be concluded if the upper limit of the 95% CIs around the difference (AR-13324 - timolol) was within 1.5 mmHg at all time points and was within 1.0 mmHg at a majority of the time points.
Statistical Test of Hypothesis P-Value <0.0001
Comments Calculated p-value
Method ANCOVA
Comments Statistical analysis applies at all 3 timepoints on Day 15, Day 43, and Day 90
2.Secondary Outcome
Title Extent of Exposure
Hide Description Exposure to study medication in days for all treatment groups.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title AR-13324 Ophthalmic Solution 0.02% & Placebo Timolol Maleate Ophthalmic Solution 0.5% BID
Hide Arm/Group Description:
1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU)
1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
Overall Number of Participants Analyzed 203 208
Mean (Standard Deviation)
Unit of Measure: days
82.8  (21.44) 87.4  (15.53)
Time Frame Adverse event data was collected during the course of the 90-day treatment period.
Adverse Event Reporting Description 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.
 
Arm/Group Title AR-13324 Ophthalmic Solution 0.02% & Placebo Timolol Maleate Ophthalmic Solution 0.5% BID
Hide Arm/Group Description 1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU) 1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
All-Cause Mortality
AR-13324 Ophthalmic Solution 0.02% & Placebo Timolol Maleate Ophthalmic Solution 0.5% BID
Affected / at Risk (%) Affected / at Risk (%)
Total   0/203 (0.00%)      0/208 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
AR-13324 Ophthalmic Solution 0.02% & Placebo Timolol Maleate Ophthalmic Solution 0.5% BID
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/203 (1.48%)      4/208 (1.92%)    
Cardiac disorders     
Congestive Heart Failure  1  0/203 (0.00%)  0 1/208 (0.48%)  1
Exacerbation of Coronary Artery Disease  1  1/203 (0.49%)  1 0/208 (0.00%)  0
Infections and infestations     
Pneumonia  1  0/203 (0.00%)  0 1/208 (0.48%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate Cancer  1  1/203 (0.49%)  1 0/208 (0.00%)  0
Nervous system disorders     
Left Upper Extremity Numbness  1  0/203 (0.00%)  0 1/208 (0.48%)  1
Stroke (CVA)  1  0/203 (0.00%)  0 1/208 (0.48%)  1
Reproductive system and breast disorders     
Worsening of Adenomyosis  1  0/203 (0.00%)  0 1/208 (0.48%)  1
Respiratory, thoracic and mediastinal disorders     
Acute Respiratory Failure  1  0/203 (0.00%)  0 1/208 (0.48%)  1
Vascular disorders     
Hypertension  1  1/203 (0.49%)  1 0/208 (0.00%)  0
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AR-13324 Ophthalmic Solution 0.02% & Placebo Timolol Maleate Ophthalmic Solution 0.5% BID
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   145/203 (71.43%)      75/208 (36.06%)    
Eye disorders     
Conjunctival hyperemia  1  108/203 (53.20%)  17/208 (8.17%) 
Conjunctival Haemmorrhage  1  32/203 (15.76%)  2/208 (0.96%) 
Cornea Verticillata  1  12/203 (5.91%)  0/208 (0.00%) 
Erythema of Eyelid  1  12/203 (5.91%)  0/208 (0.00%) 
Vision Blurred  1  11/203 (5.42%)  1/208 (0.48%) 
General disorders     
Instillation Site Pain  1  30/203 (14.78%)  42/208 (20.19%) 
Instillation Site Erythema  1  24/203 (11.82%)  4/208 (1.92%) 
Investigations     
Vital Dye Staining Cornea Present  1  17/203 (8.37%)  19/208 (9.13%) 
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Nancy Ramirez-Davis, Director Clinical Project Management
Organization: Aerie Pharmaceuticals, Inc.
Phone: 908-947-3543
Responsible Party: Aerie Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02207491     History of Changes
Other Study ID Numbers: AR-13324-CS301
First Submitted: July 31, 2014
First Posted: August 4, 2014
Results First Submitted: January 17, 2018
Results First Posted: April 13, 2018
Last Update Posted: April 13, 2018