BOL-303259-X With Timolol 0.5% in Subjects With Open-Angle Glaucoma or Ocular Hypertension (Constellation)

A Randomized, Single-Center, Open-Label, Crossover Study Comparing the Efficacy of BOL-303259-X Ophthalmic Solution With Timolol Maleate Ophthalmic Solution 0.5% in Subjects With Open-Angle Glaucoma or Ocular Hypertension.

This clinical investigation is being performed to compare the effect of BOL-303259-X dosed once daily (QD) with timolol maleate 0.5% dosed twice daily (BID) in reducing intraocular pressure (IOP) measured over a 24-hour period in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have a diagnosis of OAG or OHT in 1 or both eyes.
• Subjects who are treatment-naïve must meet the following IOP requirements at Visit 1 (Screening), and pretreated subjects must meet the following IOP requirements at Visit 2 (Washout): Intraocular pressure ≥ 22 mmHg in at least 1 eye and ≤ 36 mmHg in both eyes.

Exclusion Criteria:

• Subjects who have been exposed to BOL-303259-X within 3 months prior to Visit 1 (Screening).
• Subjects with a history or presence of chronic generalized systemic disease that the Investigator feels might increase the risk to the subject or confound the results of the study.
• Subjects with an irregular daily sleep schedule.
• Subjects who are unable to wear sleep monitoring device for 7 days prior to laboratory study.
• Subjects with an anticipated need to initiate or modify medication (systemic or topical) that is known to affect IOP.
• Subjects for whom concomitant use of medications may interact with the safety or efficacy of a nitric oxide.
• Subjects with known hypersensitivity or contraindications to latanoprost or any of the ingredients in the study drugs.
• Subjects who are expected to require treatment with ocular or systemic corticosteroids.
• Subjects who are in need of any other topical or systemic treatment of OAG or OHT.
• Subjects who are unable to discontinue contact lens use during and for 24 hours before the laboratory study.
• Subjects with a central corneal thickness greater than 600 μm in either eye.
• Subjects with any condition that prevents reliable applanationtonometry in either eye.
• Subjects with advanced glaucoma and subjects with a cup/disc ratio greater than 0.8 or a history of split fixation, or a field loss threatening fixation in either eye.
• Subjects with previous or active corneal disease.
• Subjects with a history of severe dry eye.
• Subjects with active optic disc hemorrhage.
• Subjects with a history of central/branch retinal vein or artery occlusion.
• Subjects with a history of macular edema.
• Subjects with very narrow angles and subjects with angle closure, congenital, and secondary glaucoma, and subjects with history of angle closure in either eye.
• Subjects with a diagnosis of a clinically significant or progressive retinal disease in either eye.
• Subjects with any intraocular infection or inflammation within 3 months prior to Visit 1 (Screening).
• Subjects with a history of ocular laser surgery within the 3 months prior to Visit 1 (Screening).
• Subjects with a history of incisional ocular surgery or severe trauma within 3 months prior to Visit 1 (Screening).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Timolol Maleate; Timolol maleate ophthalmic solution 0.5% administered 1 drop BID once in morning and once in the evening for 4 weeks.	Drug: Timolol maleate; Topical ophthalmic solution
Experimental: BOL-303259-X; BOL-303259-X topical ophthalmic solution administered 1 drop QD in the evening for 4 weeks.	Drug: BOL-303259-X; Topical ophthalmic solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24 Hour IOP	Supine intraocular pressure (IOP) measured in the study eye following 4 weeks of treatment	after 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour Ocular Perfusion Pressure	Sitting Ocular Perfusion Pressure = 95/140 x mean arterial blood pressure - IOP; Supine Ocular Perfusion Pressure = 115/130 x mean arterial blood pressure - IOP; the nocturnal time frame encompassed measures taken at 10pm, 12am, 2am and 4 am; whereas the diurnal time frame encompassed measures taken at 6am, 8am, 10am, 12pm, 2pm, 4pm, 6pm, and 8pm.	after 4 weeks of treatment
IOP Area Under the Curve Over 24 Hours	The Area Under the Curve(AUC) is the weighted average of IOP over all 24-hour IOP assessment times (2pm, 4pm, 6pm, 8pm, 10pm, 12am, 2am, 4am, 6am, 8am, 10am, 12pm). The AUC was calculated using the trapezoidal rule.	after 4 weeks of treatment

Collaborators and Investigators

• Sponsor: Bausch & Lomb Incorporated

Publications and helpful links

General Publications

• Liu JHK, Slight JR, Vittitow JL, Scassellati Sforzolini B, Weinreb RN. Efficacy of Latanoprostene Bunod 0.024% Compared With Timolol 0.5% in Lowering Intraocular Pressure Over 24 Hours. Am J Ophthalmol. 2016 Sep;169:249-257. doi: 10.1016/j.ajo.2016.04.019. Epub 2016 Jul 22.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: October 12, 2012
• First Submitted That Met QC Criteria: October 12, 2012
• First Posted (Estimate): October 16, 2012

Study Record Updates

• Last Update Posted (Actual): September 4, 2018
• Last Update Submitted That Met QC Criteria: August 3, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• 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: 803