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A Double-masked, Randomized, Multi-center, Active-controlled, Parallel, 12-month Study Assessing the Safety and Ocular Hypotensive Efficacy of AR-13324 Ophthalmic Solution, 0.02% q.d. and b.i.d. Compared to Timolol Maleate Ophthalmic Solution, 0.5% b.i.d. in Patients With Elevated Intraocular Pressure

Trial Profile

A Double-masked, Randomized, Multi-center, Active-controlled, Parallel, 12-month Study Assessing the Safety and Ocular Hypotensive Efficacy of AR-13324 Ophthalmic Solution, 0.02% q.d. and b.i.d. Compared to Timolol Maleate Ophthalmic Solution, 0.5% b.i.d. in Patients With Elevated Intraocular Pressure

Status: Completed
Phase of Trial: Phase III

Latest Information Update: 07 Nov 2021

At a glance

  • Drugs Netarsudil (Primary) ; Timolol
  • Indications Ocular hypertension; Open-angle glaucoma
  • Focus Registrational; Therapeutic Use
  • Acronyms Rocket 2
  • Sponsors Aerie Pharmaceuticals
  • Most Recent Events

    • 18 Dec 2017 According to an Aerie Pharmaceuticals media release, the US FDA has approved Rhopressa (netarsudil ophthalmic solution) 0.02% for the lowering of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.
    • 13 Oct 2017 According to an Aerie Pharmaceuticals media release, the Dermatologic and Ophthalmic Drugs Advisory Committee of the US FDA has voted in favor of Rhopressa™ (netarsudil ophthalmic solution) 0.02%.
    • 20 Sep 2017 According to an Aerie Pharmaceuticals media release, a meeting of the Dermatologic and Ophthalmic Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) has been scheduled with the company for October 13, 2017 to review the NDA for Rhopressa (netarsudil ophthalmic solution) 0.02% for the treatment of patients with open-angle glaucoma or ocular hypertension.

Trial Overview

Outcome

Primary endpoint met - positive

Purpose

This pivotal noninferiority trial compared the efficacy and tolerability of AR 13324 [Rhopressa] and timolol in patients with glaucoma and elevated intraocular pressure.

Comments

The US FDA approved Rhopressa (netarsudil ophthalmic solution) 0.02% for the lowering of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension (as of 18th Dec 2017).

This is one of three trials in the phase III registrational programme for AR 13324 [see also trial profile 700239568 and 700247331]. According to a company media release, Aerie Pharmaceuticals plans to enrol approximately 1300 patients in these three trials.

Primary Endpoints

Met on 16 Sep 2015

Intraocular pressure (IOP)

Non-inferiority of IOP-lowering for Rhopressa compared with timolol
Primary endpoint range to include patients with baseline intraocular pressures (IOPs) ranging from above 20 mmHg (millimeters of mercury) to below 25 mmHg [1]

Other Endpoints

Extent of Exposure

description: Exposure to study medication in days for all treatment groups
time_frame: 12 Months [2]

Diseases Treated

Indication Qualifiers Patient Segments
Ocular hypertension treatment -
Open-angle glaucoma treatment -

Biomarker

NCT Number Biomarker Name Biomarker Function
NCT02207621 Maleic acid Arm Group Label, Official Title
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Subjects

  • Subject Type patients
  • Number

    Planned: 690

    Actual: 756

  • Sex male & female
  • Age Group ≤ 99 years (mean age -60 years); adolescent; adult; child; elderly; infant; neonate

Patient Inclusion Criteria

Subject inclusion criteria 1. 0-2 years of age and 18 years or greater 2. Diagnosis of open angle glaucoma or ocular hypertension 3. Unmedicated (post-washout) intraocular pressure (IOP) >20 mm Hg and < 27 mm Hg in the study eye at 2 qualification visits 4. Corrected visual acuity in each eye equivalent to 20/200 5. Able and willing to give signed informed consent (parent or guardian consent for pediatric patient) and follow study instructions Subject

Patient 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. Intraocular pressure ≥27 mm Hg (unmedicated) in both eyes or use of more than two ocular hypotensive medications within 30 days of screening. Note: fixed dose combinations count as two medications. 3. Known hypersensitivity to any component of the formulations to be used (benzalkonium chloride, etc.), to topical anesthetics or beta-adrenoceptor antagonists. 4. Previous glaucoma intraocular surgery or glaucoma laser procedures in either eye 5. Refractive surgery in either eye. 6. Ocular trauma in either eye within the six months prior to screening, or ocular surgery or non-refractive laser treatment within the three months prior to screening. 7. Recent or current evidence of ocular infection or inflammation in either eye. Current evidence of clinically significant blepharitis, conjunctivitis, or a history of herpes simplex or zoster keratitis at screening in either eye. 8. Ocular medication in either eye of any kind within 30 days of screening. 9. Clinically significant ocular disease in either eye (e.g., corneal edema, 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. 10. Central corneal thickness in either eye greater than 600 µm at screening. 11. Any abnormality in either eye preventing reliable applanation tonometry of either eye. Systemic: 12. Clinically relevant abnormalities (as determined by the investigator) in laboratory tests at screening which may impact the study. 13. Known hypersensitivity or contraindication to beta-adrenoceptor antagonists (e.g., chronic obstructive pulmonary disease or bronchial asthma; abnormally low blood pressure or heart rate; second or third degree heart block or congestive heart failure; severe diabetes). 14. Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia gravis, hepatic, renal, endocrine or cardiovascular disorders) which might interfere with the study. 15. Participation in any investigational study within 30 days prior to screening. 16. Changes of systemic medication that could have an effect on intraocular pressure within 30 days prior to screening, or anticipated during the study. 17. 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..

Trial Details

Identifiers

Identifier Owner
NCT02207621 ClinicalTrials.gov: US National Institutes of Health
AR13324CS302 -

Organisations

  • Sponsors Aerie Pharmaceuticals
  • Affiliations Aerie Pharmaceuticals

Trial Dates

  • Initiation Dates

    Planned : 01 Jun 2014

    Actual : 11 Jul 2014

  • Primary Completion Dates

    Planned : 01 Aug 2015

    Actual : 01 Mar 2016

  • End Dates

    Planned : 01 Jun 2016

    Actual : 01 Mar 2016

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
NetarsudilPrimary Drug Ophthalmic Drops, Solution
Timolol Ophthalmic Drops, Solution

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) Drug: AR-13324 Ophthalmic Solution 0.02% (1 drop once daily (QD), PM, OU) Other Name: Netarsudil Other: Placebo (1 drop QD, AM, OU)

Timolol maleate Ophthalmic Solution 0.5% BID

1 drop twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU) Drug: Timolol maleate Ophthalmic Solution 0.5% BID (1 drop BID, AM/PM, 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) Drug: AR-13324 Ophthalmic Solution 0.02% BID (1 drop BID, AM/PM, OU) Other Name: Netarsudil

Results

Adverse events

Phase III: Interim safety data from the phase III ROCKET 2 trial showed that netarsudil mesylate was generally safe and well tolerated. The most common adverse event was hyperaemia, which was reported as increased in 30% of patients and regarded as mild in 76% of patients. At 12 month, 70% of patients with prior conjunctival hyperemia had no hyperemia. Other adverse events observed were conjunctival hemorrhages, cornea verticillata, instillation site pain and blurry vision (5%- 23%). Netarsudil mesylate dosed twice-daily generated higher incidence of adverse events [3] [1] .

Publications

  1. Aerie Pharmaceuticals. Aerie Pharmaceuticals Reports Positive Rhopressa(TM) Phase 3 Efficacy Results. Media-Rel 2015;.

    Media Release
  2. Aerie Pharmaceuticals. Aerie Pharmaceuticals Reports Positive RhopressaTM QD (netarsudil ophthalmic solution) 0.02% 12 Month Interim Safety Results for Rocket 2. Media-Rel 2016;.

    Media Release
  3. Serle JB, Katz LJ, McLaurin E, Heah T, Ramirez-Davis N, Usner DW, et al. Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). Am-J-Ophthalmol 2018;186116-127.

    PubMed | CrossRef Fulltext
  4. Kahook MY, Serle JB, Mah FS, Kim T, Raizman MB, Heah T, et al. Long-term Safety and Ocular Hypotensive Efficacy Evaluation of Netarsudil Ophthalmic Solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2). Am-J-Ophthalmol 2019;200130-137.

    PubMed | CrossRef Fulltext

Authors

Author Total Publications First Author Last Author
Aerie Pharmaceuticals 2 2 2
Heah T 2 - -
Kahook MY 1 1 -
Katz LJ 1 - -
Kim T 1 - -
Kopczynski CC 2 - -
Mah FS 1 - -
McLaurin E 1 - -
Novack GD 2 - -
Raizman MB 1 - -
Ramirez-Davis N 2 - -
ROCKET-1 and ROCKET-2 Study Groups 1 - 1
ROCKET-2 Study Group 1 - 1
Serle JB 2 1 -
Usner DW 2 - -

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Brian Levy, O.D., M.S. Aerie Pharmaceuticals, Inc.
-

Centres

Centre Name Location Trial Centre Country
Aerie Pharmaceuticals
-
USA
Aerie Pharmaceuticals, Inc.
-
-

Trial History

Event Date Event Type Comment
01 Apr 2019 Results Results, evaluating long term (over 12 months) safety and efficacy of Netarsudil ophthalmic solution for intraocular pressure treatment, published in the American Journal of Ophthalmology Updated 02 Jan 2020
09 Apr 2018 Other trial event Last checked against ClinicalTrials.gov record. Updated 09 Apr 2018
06 Apr 2018 Biomarker Update Biomarkers information updated Updated 07 Nov 2021
01 Feb 2018 Results Results evaluating the efficacy and ocular and systemic safety of netarsudil 0.02% ophthalmic solution from ROCKET 1 and ROCKET 2 trial published in the American Journal of Ophthalmology Updated 05 Feb 2019
18 Dec 2017 Other trial event According to an Aerie Pharmaceuticals media release, the US FDA has approved Rhopressa (netarsudil ophthalmic solution) 0.02% for the lowering of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Updated 21 Dec 2017
13 Oct 2017 Other trial event According to an Aerie Pharmaceuticals media release, the Dermatologic and Ophthalmic Drugs Advisory Committee of the US FDA has voted in favor of Rhopressa™ (netarsudil ophthalmic solution) 0.02%. Updated 17 Oct 2017
20 Sep 2017 Other trial event According to an Aerie Pharmaceuticals media release, a meeting of the Dermatologic and Ophthalmic Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) has been scheduled with the company for October 13, 2017 to review the NDA for Rhopressa (netarsudil ophthalmic solution) 0.02% for the treatment of patients with open-angle glaucoma or ocular hypertension. Updated 26 Sep 2017
15 May 2017 Other trial event According to an Aerie Pharmaceuticals media release, the company has received notification from U.S. Food and Drug Administration (FDA) that the FDA has completed its initial 60 day review of the RhopressaTM NDA (new drug application) and determined that the application is sufficiently complete to permit a substantive review. The FDA has set the PDUFA goal date for the completion of the FDA's review of the RhopressaTM NDA for February 28, 2018. Updated 22 May 2017
01 Mar 2017 Other trial event According to an Aerie Pharmaceuticals media release, on February 28, 2017 the company has resubmitted its NDA (New Drug Application) for Rhopressa to the FDA after notification by its contract drug product manufacturer that the vendor's Tampa, Florida facility is now ready for pre-approval inspection by the FDA for Rhopressa. Updated 07 Mar 2017
23 Dec 2016 Other trial event According to an Aerie Pharmaceuticals media release, the company expects to resubmit the Rhopressa NDA filing near the end of the first quarter of 2017 after receiving notification from the contract drug product manufacturer that the manufacturing line related to the product is inspection ready. Updated 29 Dec 2016
27 Oct 2016 Other trial event According to an Aerie Pharmaceuticals media release, the company has withdrawn the NDA (new drug application) that was submitted to the FDA. The filing was withdrawn as the result of a third party manufacturing facility in Tampa, Florida not being ready for pre-approval inspection by the FDA. The drug product contract manufacturer has advised Aerie and the FDA that it expects to be prepared for FDA inspection in January 2017, and Aerie expects to resubmit the Rhopressa NDA filing at that time. Updated 10 Nov 2016
06 Sep 2016 Other trial event According to an Aerie Pharmaceuticals media release, the company has submitted a New Drug Application (NDA) to the US FDA for netarsudil ophthalmic solution (Rhopressa) to treat patients with glaucoma based on results from Rocket 1 and Rocket 2 trials. Updated 22 Sep 2016
11 Jul 2016 Status change - completed Status changed from active, no longer recruiting to completed. Updated 14 Jul 2016
22 Feb 2016 Other trial event Top-line results from this trial will be presented at the American Glaucoma Society (AGS) 26th Annual Meeting, according to an Aerie Pharmaceuticals media release. Updated 25 Feb 2016
17 Feb 2016 Other trial event According to an Aerie Pharmaceuticals media release, company is planning to submit NDA to the FDA and 90-day efficacy readout is expected in the third quarter of 2016. Updated 19 Feb 2016
17 Feb 2016 Interim results According to an Aerie Pharmaceuticals media release, company reported the successful 12-month interim safety results of this trial. Updated 19 Feb 2016
16 Sep 2015 Results Efficacy results published in the Aerie Pharmaceuticals media release. Updated 18 Sep 2015
16 Sep 2015 Other trial event According to an Aerie Pharmaceuticals media release, safety results are expected at the end of 2015 or early 2016. Updated 17 Sep 2015
16 Sep 2015 Endpoint met Primary endpoint has been met (Intraocular pressure (IOP)), as reported in Aerie Pharmaceuticals media release. Updated 17 Sep 2015
15 Jun 2015 Other trial event According to Aerie Pharmaceuticals media release, FDA has agreed to change the primary endpoint to include patients with baseline intraocular pressures ranging from 20 to 25mmHg instead of 20 to 27mmHg in this trial. Updated 16 Jun 2015
24 Mar 2015 Status change - active, no longer recruiting According to Aerie Pharmaceuticals media release, status changed from recruiting to active, no longer recruiting. Updated 26 Mar 2015
02 Dec 2014 Other trial event Enrolment is proceeding on schedule, according to an Aerie Pharmaceuticals media release. Updated 05 Dec 2014
11 Nov 2014 Other trial event As per media release, the company expects to submit an NDA filing by mid-2016 Updated 24 Dec 2014
13 Aug 2014 Other trial event New source identified and integrated (ClinicalTrials.gov; NCT02207621). Updated 13 Aug 2014
14 Jul 2014 Other trial event According to an Aerie Pharmaceuticals media release, 3-month efficacy results are expected in mid-2015. Updated 18 Jul 2014
14 Jul 2014 Status change - recruiting Status changed from planning to recruiting according to an Aerie Pharmaceuticals media release. Updated 18 Jul 2014
10 Dec 2013 New trial record New trial record Updated 10 Dec 2013

References

  1. Aerie Pharmaceuticals. Aerie Pharmaceuticals Reports Positive Rhopressa(TM) Phase 3 Efficacy Results. Media-Rel 2015;.

    Media Release
  2. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.

    Available from: URL: http://clinicaltrials.gov
  3. Aerie Pharmaceuticals. Aerie Pharmaceuticals Reports Positive RhopressaTM QD (netarsudil ophthalmic solution) 0.02% 12 Month Interim Safety Results for Rocket 2. Media-Rel 2016;.

    Media Release
  4. Aerie Pharmaceuticals. Aerie Pharmaceuticals Reports Third Quarter 2014 Financial Results and Provides Business and Product Development Update. Media-Rel 2014;.

    Media Release
  5. Aerie Pharmaceuticals. Aerie Pharmaceuticals Receives Positive Feedback from FDA. Media-Rel 2015;.

    Media Release
  6. Aerie Pharmaceuticals. Aerie Pharmaceuticals Announces Resubmission of NDA for RhopressaT (netarsudil ophthalmic solution) 0.02%. Media-Rel 2017;.

    Media Release
  7. Serle JB, Katz LJ, McLaurin E, Heah T, Ramirez-Davis N, Usner DW, et al. Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). Am-J-Ophthalmol 2018;186116-127.

    PubMed | CrossRef Fulltext
  8. Aerie Pharmaceuticals. Aerie Pharmaceuticals Initiates Phase 3 Registration Trials of RhopressaTM, Novel Triple-Action Product to Lower Intraocular Pressure in Patients with Glaucoma. Media-Rel 2014;.

    Media Release
  9. Aerie Pharmaceuticals. Aerie Pharmaceuticals Announces FDA Advisory Committee Meeting for Rhopressa(T) (netarsudil ophthalmic solution) 0.02%. Media-Rel 2017;.

    Media Release
  10. Kahook MY, Serle JB, Mah FS, Kim T, Raizman MB, Heah T, et al. Long-term Safety and Ocular Hypotensive Efficacy Evaluation of Netarsudil Ophthalmic Solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2). Am-J-Ophthalmol 2019;200130-137.

    PubMed | CrossRef Fulltext
  11. Aerie Pharmaceuticals. Aerie Pharmaceuticals Announces FDA Acceptance of NDA Submission for Rhopressa(TM) (netarsudil ophthalmic solution) 0.02%. Media-Rel 2017;.

    Media Release
  12. Aerie Pharmaceuticals. Aerie Pharmaceuticals Submits New Drug Application to U.S. Food and Drug Administration for Rhopressa(TM) (netarsudil ophthalmic solution) 0.02%. Media-Rel 2016;.

    Media Release
  13. Aerie Pharmaceuticals. Aerie Pharmaceuticals Announces FDA Advisory Committee Vote in Favor of Rhopressa(T) (netarsudil ophthalmic solution) 0.02%. Media-Rel 2017;.

    Media Release
  14. Aerie Pharmaceuticals. Aerie Pharmaceuticals Inc. Initiates Phase 3 Safety-Only Registration Trial in Canada of RhopressaTM in Patients with Glaucoma. Media-Rel 2014;.

    Media Release
  15. Aerie Pharmaceuticals. Aerie Pharmaceuticals Provides Update on Timing of NDA Filing for Rhopressa(TM)(netarsudil ophthalmic solution) 0.02%. Media-Rel 2016;.

    Media Release
  16. Aerie Pharmaceuticals. Aerie Pharmaceuticals Completes Enrollment in Phase 3 Registration Trial (Rocket 1) of Rhopressa(Tm), Novel Triple-Action Product to Lower Intraocular Pressure in Patients with Glaucoma. Media-Rel 2014;.

    Media Release
  17. Aerie Pharmaceuticals. Aerie Pharmaceuticals Announces Four New Abstracts to be Presented at the American Glaucoma Society 26th Annual Meeting Next Week. Media-Rel 2016;.

    Media Release
  18. Aerie Pharmaceuticals Inc. Aerie Pharmaceuticals Reports Third Quarter 2013 Financial Results and Provides Business and Product Development Update. Media-Rel 2013;.

    Media Release
  19. Aerie Pharmaceuticals. Aerie Pharmaceuticals Completes Enrollment in Second Phase 3 Registration Trial (Rocket 2) of Rhopressa(Tm), Novel Triple-Action Product to Lower Intraocular Pressure in Patients with Glaucoma. Media-Rel 2015;.

    Media Release
  20. Aerie Pharmaceuticals. Aerie Pharmaceuticals Reports Positive Topline Efficacy Results of Rocket 4 Phase 3 Trial of RhopressaTM (netarsudil ophthalmic solution) 0.02%. Media-Rel 2016;.

    Media Release
  21. Aerie Pharmaceuticals. Aerie Pharmaceuticals Announces U.S. FDA Approval of Rhopressa(R)(netarsudil ophthalmic solution) 0.02% for the Lowering of Elevated Intraocular Pressure in Patients with Open-Angle Glaucoma or Ocular Hypertension. Media-Rel 2017;.

    Media Release
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