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A Double-masked, Randomized, Multi-center, Active-controlled, Parallel, 3-month Study Assessing the Safety and Ocular Hypotensive Efficacy of AR-13324 Ophthalmic Solution, 0.02% Compared to Timolol Maleate Ophthalmic Solution, 0.5% in Patients With Elevated Intraocular Pressure

Trial Profile

A Double-masked, Randomized, Multi-center, Active-controlled, Parallel, 3-month Study Assessing the Safety and Ocular Hypotensive Efficacy of AR-13324 Ophthalmic Solution, 0.02% Compared to Timolol Maleate Ophthalmic Solution, 0.5% 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 Glaucoma; Ocular hypertension
  • Focus Registrational; Therapeutic Use
  • Acronyms Rocket 1
  • 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 not met - negative

Purpose

This pivotal non-inferiority 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 700239574 and 700247331].

Primary Endpoints

Not met, 23 Apr 2015

Intraocular pressure (IOP)

Non-inferiority of IOP-lowering for Rhopressa compared with timolol [1]

Other Endpoints

Extent of Exposure

description: Exposure to study medication in days for all treatment groups.
time_frame: 3 months [2]

Diseases Treated

Indication Qualifiers Patient Segments
Glaucoma treatment -
Ocular hypertension treatment -

Biomarker

NCT Number Biomarker Name Biomarker Function
NCT02207491 Maleic acid Arm Group Description, 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: 400

    Actual: 411

  • Sex male & female
  • Age Group ≥ 18 years; Adult

Patient Inclusion Criteria

Subject 1. 0-2 years of age and 18 years or greater. 2. Diagnosis of open angle glaucoma or ocular hypertension 3. Unmedicated (post-washout) IOP (Intraocular Pressure) >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 (individuals who are excluded for this criterion are not allowed to attempt requalification), 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
NCT02207491 ClinicalTrials.gov: US National Institutes of Health
AR13324CS301 -

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 2015

  • End Dates

    Planned : 01 Aug 2015

    Actual : 01 Mar 2015

Other Details

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

Interventions

Drugs Route Formulation
NetarsudilPrimary Drug Ophthalmic Drops
Timolol Ophthalmic Drops

Timolol maleate Ophthalmic Solution 0.5% BID

1 drop Timolol maleate twice daily (BID) in the morning (AM) & 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% & 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)

Results

Publications

  1. Aerie Pharmaceuticals. Aerie Pharmaceuticals Reports Initial RhopressaTM Phase 3 Efficacy Results. Media-Rel 2015;.

    Media Release
  2. 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

Authors

Author Total Publications First Author Last Author
Aerie Pharmaceuticals 1 1 1
Heah T 1 - -
Katz LJ 1 - -
Kopczynski CC 1 - -
McLaurin E 1 - -
Novack GD 1 - -
Ramirez-Davis N 1 - -
ROCKET-1 and ROCKET-2 Study Groups 1 - 1
Serle JB 1 1 -
Usner DW 1 - -

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
18 Apr 2018 Other trial event Last checked against ClinicalTrials.gov record. Updated 18 Apr 2018
13 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 06 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
01 Mar 2016 Results Results published in the British Journal of Ophthalmology Updated 10 Sep 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
28 Apr 2015 Other trial event According to an Aerie Pharmaceuticals media release, additional findings from this trial will be discussed during a live conference call and webcast by the company on 7th May 2015. Updated 30 Apr 2015
23 Apr 2015 Results Results published in Aerie Pharmaceuticals Media Release. Updated 05 May 2015
23 Apr 2015 Endpoint not met Primary endpoint has not been met (Intraocular pressure (IOP)), according to Aerie Pharmaceuticals media release. Updated 05 May 2015
23 Apr 2015 Status change - completed Status changed from active, no longer recruiting to completed according to an Aerie Pharmaceuticals media release. Updated 30 Apr 2015
12 Jan 2015 Other trial event Efficacy results are expected in May 2015, according to an Aerie Pharmaceuticals media release. Updated 15 Jan 2015
02 Dec 2014 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting, 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; NCT02207491) Updated 13 Aug 2014
14 Jul 2014 Status change - recruiting Status changed from planning to recruiting according to an Aerie Pharmaceuticals media release. Updated 18 Jul 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
10 Dec 2013 New trial record New trial record Updated 10 Dec 2013

References

  1. Aerie Pharmaceuticals. Aerie Pharmaceuticals Reports Initial RhopressaTM 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 Third Quarter 2014 Financial Results and Provides Business and Product Development Update. Media-Rel 2014;.

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

    Media Release
  5. 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
  6. 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
  7. Aerie Pharmaceuticals. Aerie Pharmaceuticals Announces FDA Advisory Committee Meeting for Rhopressa(T) (netarsudil ophthalmic solution) 0.02%. Media-Rel 2017;.

    Media Release
  8. Aerie Pharmaceuticals. Aerie Pharmaceuticals Announces FDA Acceptance of NDA Submission for Rhopressa(TM) (netarsudil ophthalmic solution) 0.02%. Media-Rel 2017;.

    Media Release
  9. 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
  10. Aerie Pharmaceuticals. Aerie Pharmaceuticals to Announce First Quarter 2015 Financial Results and Host Conference Call on Thursday, May 7, 2015. Media-Rel 2015;.

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

    Media Release
  12. 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
  13. Aerie Pharmaceuticals. Aerie Pharmaceuticals Announces Acceleration of Expected Timeline for Reporting Efficacy Results from Phase 3 Registration Trial (Rocket 1) of RhopressaTM. Media-Rel 2015;.

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

    Media Release
  15. 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
  16. 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
  17. Aerie Pharmaceuticals Inc. Aerie Pharmaceuticals Reports Third Quarter 2013 Financial Results and Provides Business and Product Development Update. Media-Rel 2013;.

    Media Release
  18. 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
  19. 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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