Comparing the Safety and Efficacy of BOL-303259-X Ophthalmic Solution With Timolol Maleate Ophthalmic Solution in Subjects With Open-Angle Glaucoma or Ocular Hypertension (LUNAR)

A Randomized, Multicenter, Double-Masked, Parallel-Group Study Comparing the Safety and Efficacy of BOL-303259-X Ophthalmic Solution With Timolol Maleate Ophthalmic Solution 0.5% in Subjects With Open-Angle Glaucoma or Ocular Hypertension

In participants with a diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT), the primary objective is to demonstrate that the mean IOP reduction after 3 months of treatment with BOL-303259-X once daily (QD) is non-inferior to timolol maleate 0.5% twice daily (BID). The secondary objective is to demonstrate the superiority of BOL-303259-X QD to timolol maleate 0.5% BID. This assessment will be performed if the non-inferiority of BOL-303259-X QD to timolol maleate 0.5% BID is determined. An open label safety phase will be conducted at the end of Visit 6 (3 months) where all participants will receive BOL-303259-X QD for an additional 3 months.

Study Overview

• Status: Completed
• Conditions: Ocular Hypertension; Open-Angle Glaucoma
• Intervention / Treatment: Drug: BOL-303259-X; Drug: BOL-303259-X; Drug: Timolol

• Study Type: Interventional
• Enrollment (Actual): 420
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14609
      • Bausch & Lomb Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must have a diagnosis of OAG (including pigmentary or pseudoexfoliative) or OHT in 1 or both eyes.
• Participants must meet the following IOP requirements at Visit 3
• mean/median IOP ≥ 24 mmHg at a minimum of 2 time points in the same eye
• IOP ≤ 36 mmHg at all 3 measurement time points in both eyes.
• Participants with a best-corrected visual acuity (BCVA), using the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol, of +0.7 logMAR units (Snellen equivalent of approximately 20/100) or better in either eye.

Exclusion Criteria:

• Participants with known hypersensitivity or contraindications to latanoprost, NO treatment, timolol maleate, other beta-adrenergic receptor antagonists or any of the ingredients in the study drugs.
• Participants with a central corneal thickness greater than 600 μm in either eye.
• Participants with advanced glaucoma and participants with a cup/disc ratio greater than 0.8 or a history of split fixation, or a field loss threatening fixation in either eye.
• Participants who do not have an intact posterior capsule in either eye .
• Participants with aphakia in either eye.
• Participants with previous or active corneal disease in either eye.
• Participants with current or a history of severe dry eye in either eye.
• Participants with current or a history of optic disc hemorrhage in either eye.
• Participants with current or a history of central/branch retinal vein or artery occlusion in either eye.
• Participants with current or a history of macular edema in either eye.
• Participants with very narrow angles (3 quadrants with less than Grade 2 according to Shaffer's anterior chamber angle grading system) and participants with angle closure,congenital, and secondary glaucoma, and participants with history of angle closure in either eye.
• Participants with a diagnosis of a clinically significant or progressive retinal disease in either eye.
• Participants with any intraocular infection or inflammation in either eye within 3 months(90 days) prior to Visit 1 (Screening).
• Participants with a history of ocular laser surgery in either eye within the 3 months(90 days) prior to Visit 1 (Screening).
• Participants with a history of incisional ocular surgery or severe trauma in either eye within 3 months (90 days) prior to Visit 1 (Screening).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BOL-303259-X; BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months (Visit 6) into the study eye(s).	Drug: BOL-303259-X; BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning; Drug: BOL-303259-X; All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).
Active Comparator: Timolol; Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months (Visit 6) into study eye(s).	Drug: BOL-303259-X; BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning; Drug: BOL-303259-X; All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).; Drug: Timolol; Timolol will be administered BID once in the morning and once in the evening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean IOP	Mean intraocular pressure (IOP) in the study eye measured at the specified time points: 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3).	8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IOP ≤ 18 mm Hg	Percentage of participants with IOP ≤ 18 mm Hg consistently at all 9 time points in the first 3 months	8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)
IOP Reduction ≥ 25%	Percentage of participants with IOP reduction ≥ 25% consistently at all 9 time points in the first 3 months	8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Ocular and Systemic Adverse Events	Following assessments through 3 months (Visit 6), all participants, irrespective of previous randomization, converted to a single open label safety arm receiving BOL-303259-X QD in the evening for an additional 3 months through Visit 7. Adverse events were recorded throughout the comparative efficacy phase and open label extension phase.	6 months

Collaborators and Investigators

• Sponsor: Bausch & Lomb Incorporated
• Investigators: Study Director: Jason Vittitow, Bausch & Lomb Incorporated

Publications and helpful links

General Publications

• Weinreb RN, Liebmann JM, Martin KR, Kaufman PL, Vittitow JL. Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular Hypertension: Pooled Phase 3 Study Findings. J Glaucoma. 2018 Jan;27(1):7-15. doi: 10.1097/IJG.0000000000000831.
• Medeiros FA, Martin KR, Peace J, Scassellati Sforzolini B, Vittitow JL, Weinreb RN. Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: The LUNAR Study. Am J Ophthalmol. 2016 Aug;168:250-259. doi: 10.1016/j.ajo.2016.05.012. Epub 2016 May 20.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: December 11, 2012
• First Submitted That Met QC Criteria: December 12, 2012
• First Posted (Estimate): December 17, 2012

Study Record Updates

• Last Update Posted (Actual): November 21, 2018
• Last Update Submitted That Met QC Criteria: October 25, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Intraocular pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Timolol
• Other Study ID Numbers: 770