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Study Comparing the Safety and Efficacy of AR-13324 to Latanoprost in Patients With Elevated Intraocular Pressure

Sponsor
Aerie Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01731002
Collaborator
(none)
224
Enrollment
22
Locations
3
Arms
5.9
Duration (Months)
10.2
Patients Per Site
1.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Double-masked, randomized, multi-center, dose-response, active-controlled parallel-comparison of AR-13324 to latanoprost

Condition or Disease Intervention/Treatment Phase
  • Drug: AR-13324 Ophthalmic Solution 0.01%
  • Drug: AR-13324 Ophthalmic Solution 0.02%
  • Drug: Latanoprost ophthalmic solution 0.005%
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
224 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Double-masked, Randomized, Multi-center, Active-controlled, Dose-response Parallel-group Study Comparing the Safety and Ocular Hypotensive Efficacy of AR-13324 to Latanoprost in Patients With Elevated Intraocular Pressure
Study Start Date :
Nov 1, 2012
Actual Primary Completion Date :
May 1, 2013
Actual Study Completion Date :
May 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: AR-13324 Ophthalmic Solution 0.01%

1 drop to study eye once daily

Drug: AR-13324 Ophthalmic Solution 0.01%
Administered to study eye, once daily (QD) in the evening (PM) for 28 days
Experimental: AR-13324 Ophthalmic Solution 0.02%

1 drop to study eye once daily

Drug: AR-13324 Ophthalmic Solution 0.02%
Administered to study eye, QD in the PM for 28 days
Other Names:
  • Netarsudil

    		•
    Active Comparator: Latanoprost Ophthalmic Solution 0.005%

    1 drop to study eye once daily

    Drug: Latanoprost ophthalmic solution 0.005%
    Administered to study eye, QD in the PM for 28 days
    Other Names:
  • Latanoprost

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Intraocular Pressure (IOP) [Study treatment was administered for 28 days]

      The primary efficacy endpoint was the mean IOP across subjects within treatment group on each day at each post-treatment timepoint. IOP was measured at 0800, 1000, and 1600 hours on days 0, 14, and 28. IOP was also measured at 0800 hours on Day 7 and follow-up days 29 and 30.

    Secondary Outcome Measures

    1. Extent of Exposure [28 Days]

      Exposure to study medication in days for all treatment groups.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. 18 years of age or greater.

    2. Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT).

    3. Unmedicated (post-washout) Intraocular Pressure (IOP) ≥ 24 mm Hg at 2 eligibility visits (08:00 hr), 2-7 days a part, and ≥ 22 mm Hg at 10:00 and 16:00 hrs at the second qualification visit. If only one eye meets the IOP criteria it must be the same eye that met the criteria at all the qualification timepoints.

    4. Corrected visual acuity in each eye +1.0 logMAR or better by ETDRS in each eye (equivalent to 20/200).

    5. Able and willing to give signed informed consent and follow study instructions.

    Exclusion Criteria:

    Ophthalmic

    1. Glaucoma: pseudoexfoliation or pigment dispersion component, history of angle closure or narrow angles. Note: Previous laser peripheral iridotomy is NOT acceptable.

    2. IOP > 36 mm Hg.

    3. Known hypersensitivity to any component of the formulation (benzalkonium chloride, etc.), or to topical anesthetics.

    4. Previous glaucoma intraocular surgery or glaucoma laser procedures in study eye(s, e.g., laser trabeculoplasty).

    5. Refractive surgery in study eye(s) (e.g., radial keratotomy, photorefractive keratectomy (PRK), laser eye surgery (LASIK), etc.).

    6. Ocular trauma within the past six months, or ocular surgery or laser treatment within the past three months prior to screening.

    7. Evidence of ocular infection, inflammation, clinically significant blepharitis or conjunctivitis at screening (Visit 0), or a history of herpes simplex keratitis

    8. Ocular medication of any kind within 30 days of Visit 0, with the exception of a) ocular hypotensive medications (which must be washed out according to the provided schedule), b) lid scrubs (which may be used prior to, but not after Visit 0) or c) lubricating drops for dry eye (which may be used throughout the study).

    9. Clinically significant ocular disease (e.g. uveitis, severe keratoconjunctivitis sicca) which might interfere with the study, including glaucomatous damage so severe that washout of ocular hypotensive medications for one month is not judged safe (i.e., cup-disc ratio > 0.8).

    10. Central corneal thickness greater than 600 µm.

    11. Any abnormality preventing reliable applanation tonometry of either eye.

    Systemic:

    1. Clinically significant abnormalities (as determined by the treating physician) in laboratory tests at screening.

    2. Known hypersensitivity or contraindication to latanoprost.

    3. Clinically significant systemic disease (e.g., myasthenia gravis, hepatic, renal, endocrine or cardiovascular disorders) which might interfere with the study.

    4. Participation in any investigational study within 30 days prior to screening.

    5. Changes of systemic medication that could have a substantial effect on IOP within 30 days prior to screening, or anticipated during the study.

    6. Due to the current status of the preclinical safety program, women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. An adult woman is considered to be of childbearing potential unless she is one year post-menopausal or three months post-surgical sterilization. All females of childbearing potential must have a negative urine pregnancy test result at the screening examination and must not intend to become pregnant during the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Kenneth Sall, M.D. Artesia California United States 90701
    2 United Medical Research Institute Inglewood California United States 90301
    3 Aesthetic Eye Care Institute Newport Beach California United States 92657
    4 North Bay Eye Associates Petaluma California United States 94954
    5 Centre For Health Care Poway California United States 92064
    6 Clayton Eye Center Morrow Georgia United States 30260
    7 Coastal Research Associates, LLC Roswell Georgia United States 30076
    8 Bradley Kwapiszeski, MD Shawnee Mission Kansas United States 66204
    9 Taustine Eye Center Louisville Kentucky United States 40217
    10 Alan L Robin, M.D. Baltimore Maryland United States 21209
    11 Seidenberg Protzko Eye Associates Havre De Grace Maryland United States 21078
    12 Great Lakes Eye Care Saint Joseph Michigan United States 49085
    13 Ophthalmic Consultants of Long Island Lynbrook New York United States 11563
    14 Rochester Ophthalmological Group Rochester New York United States 14618
    15 Charlotte Eye Ear Nose and Throat Charlotte North Carolina United States 28210
    16 Michael E. Tepedino, M.D. High Point North Carolina United States 27262
    17 The Eye Institute Tulsa Oklahoma United States 74104
    18 Wills Eye Hospital Philadelphia Pennsylvania United States 19107
    19 Texan Eye Austin Texas United States 78731
    20 Cataract & Glaucoma Center El Paso Texas United States 79902
    21 Medical Center Ophth. Associates San Antonio Texas United States 78731
    22 Virginia Eye Consultants Norfolk Virginia United States 23502

    Sponsors and Collaborators

    • Aerie Pharmaceuticals

    Investigators

    • Study Director: Theresa Heah, MD, Aerie Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Aerie Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01731002
    Other Study ID Numbers:
    • AR-13324-CS202
    First Posted:
    Nov 21, 2012
    Last Update Posted:
    Apr 17, 2018
    Last Verified:
    Jun 1, 2016
    Keywords provided by Aerie Pharmaceuticals
    Glaucoma
    Additional relevant MeSH terms:
    Glaucoma
    Glaucoma, Open-Angle
    Ocular Hypertension
    Pharmaceutical Solutions
    Latanoprost
    Ophthalmic Solutions

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title AR-13324 Ophthalmic Solution 0.01% AR-13324 Ophthalmic Solution 0.02% Latanoprost Ophthalmic Solution 0.005%
    Arm/Group Description 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM)
    Period Title: Overall Study
    STARTED 75 72 77
    COMPLETED 71 68 74
    NOT COMPLETED 4 4 3

    Baseline Characteristics

    Arm/Group Title AR-13324 Ophthalmic Solution 0.01% AR-13324 Ophthalmic Solution 0.02% Latanoprost Ophthalmic Solution 0.005% Total
    Arm/Group Description 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM) Total of all reporting groups
    Overall Participants 75 72 77 224
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63.5
    (11.54)
    66.3
    (10.25)
    65.7
    (11.82)
    65.1
    (11.26)
    Sex: Female, Male (Count of Participants)
    Female
    42
    56%
    45
    62.5%
    45
    58.4%
    132
    58.9%
    Male
    33
    44%
    27
    37.5%
    32
    41.6%
    92
    41.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    16
    21.3%
    15
    20.8%
    15
    19.5%
    46
    20.5%
    Not Hispanic or Latino
    59
    78.7%
    57
    79.2%
    62
    80.5%
    178
    79.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    2.7%
    2
    2.8%
    0
    0%
    4
    1.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    17
    22.7%
    16
    22.2%
    19
    24.7%
    52
    23.2%
    White
    56
    74.7%
    53
    73.6%
    58
    75.3%
    167
    74.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    1
    1.4%
    0
    0%
    1
    0.4%

    Outcome Measures

    1. Primary Outcome
    Title Intraocular Pressure (IOP)
    Description The primary efficacy endpoint was the mean IOP across subjects within treatment group on each day at each post-treatment timepoint. IOP was measured at 0800, 1000, and 1600 hours on days 0, 14, and 28. IOP was also measured at 0800 hours on Day 7 and follow-up days 29 and 30.
    Time Frame Study treatment was administered for 28 days

    Outcome Measure Data

    Analysis Population Description
    Modified intent to treat (mITT) population (3 subjects were excluded, leaving 221)
    Arm/Group Title AR-13324 Ophthalmic Solution 0.01% AR-13324 Ophthalmic Solution 0.02% Latanoprost Ophthalmic Solution 0.005%
    Arm/Group Description 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM)
    Measure Participants 74 71 76
    Day 0, 0800 hours
    27.34
    (3.529)
    27.11
    (3.031)
    26.78
    (2.749)
    Day 0, 1000 hours
    25.55
    (3.411)
    25.41
    (3.024)
    25.18
    (2.719)
    Day 0, 1600 hours
    24.49
    (3.128)
    24.29
    (2.602)
    24.58
    (2.515)
    Day 7, 0800 hours
    21.89
    (4.672)
    21.15
    (4.047)
    20.03
    (3.173)
    Day 14, 0800 hours
    21.24
    (4.295)
    20.80
    (3.679)
    19.30
    (3.033)
    Day 14, 1000 hours
    19.28
    (3.581)
    18.88
    (3.461)
    18.09
    (2.884)
    Day 14, 1600 hours
    18.90
    (3.578)
    18.72
    (3.585)
    17.86
    (2.977)
    Day 28, 0800 hours
    21.95
    (4.717)
    21.24
    (4.034)
    19.24
    (2.899)
    Day 28, 1000 hours
    19.69
    (4.358)
    19.53
    (3.726)
    18.40
    (2.994)
    Day 28, 1600 hours
    18.82
    (3.281)
    19.13
    (3.656)
    18.34
    (3.052)
    2. Secondary Outcome
    Title Extent of Exposure
    Description Exposure to study medication in days for all treatment groups.
    Time Frame 28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AR-13324 Ophthalmic Solution 0.01% AR-13324 Ophthalmic Solution 0.02% Latanoprost Ophthalmic Solution 0.005%
    Arm/Group Description 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM)
    Measure Participants 75 72 77
    Mean (Standard Deviation) [days]
    27.6
    (4.07)
    26.8
    (4.6)
    27.8
    (1.35)

    Adverse Events

    Time Frame 28 Days
    Adverse Event Reporting Description
    Arm/Group Title AR-13324 Ophthalmic Solution 0.01% AR-13324 Ophthalmic Solution 0.02% Latanoprost Ophthalmic Solution 0.005%
    Arm/Group Description 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM) 1 drop to study eye once daily (QD) in the evening (PM)
    All Cause Mortality
    AR-13324 Ophthalmic Solution 0.01% AR-13324 Ophthalmic Solution 0.02% Latanoprost Ophthalmic Solution 0.005%
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/75 (1.3%) 0/72 (0%) 0/77 (0%)
    Serious Adverse Events
    AR-13324 Ophthalmic Solution 0.01% AR-13324 Ophthalmic Solution 0.02% Latanoprost Ophthalmic Solution 0.005%
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/75 (1.3%) 0/72 (0%) 2/77 (2.6%)
    Infections and infestations
    Pneumonia Streptococcal 0/75 (0%) 0/72 (0%) 1/77 (1.3%)
    Injury, poisoning and procedural complications
    Fall 0/75 (0%) 0/72 (0%) 1/77 (1.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute Leukaemia 1/75 (1.3%) 0/72 (0%) 0/77 (0%)
    Other (Not Including Serious) Adverse Events
    AR-13324 Ophthalmic Solution 0.01% AR-13324 Ophthalmic Solution 0.02% Latanoprost Ophthalmic Solution 0.005%
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 43/75 (57.3%) 45/72 (62.5%) 18/77 (23.4%)
    Eye disorders
    Conjunctival Hyperaemia 29/75 (38.7%) 34/72 (47.2%) 12/77 (15.6%)
    Ocular Hyperaemia 10/75 (13.3%) 7/72 (9.7%) 0/77 (0%)
    Lacrimation Increased 4/75 (5.3%) 5/72 (6.9%) 0/77 (0%)
    Conjunctival Haemorrhage 4/75 (5.3%) 4/72 (5.6%) 0/77 (0%)
    Foreign Body Sensation in Eyes 0/75 (0%) 5/72 (6.9%) 3/77 (3.9%)
    General disorders
    Instillation Site Pain 5/75 (6.7%) 9/72 (12.5%) 4/77 (5.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    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 of Clinical Project Management
    Organization Aerie Pharmaceuticals, Inc.
    Phone 908-947-3543
    Email nramirez@aeriepharma.com
    Responsible Party:
    Aerie Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01731002
    Other Study ID Numbers:
    • AR-13324-CS202
    First Posted:
    Nov 21, 2012
    Last Update Posted:
    Apr 17, 2018
    Last Verified:
    Jun 1, 2016