Nebivolol 0.5, 1.0, or Timolol 0.5 Suspension Compared to Timolol 0.5 Solution to Treat Glaucoma/Ocular Hypertension

NCT04910100 | Completed Phase 2 Results FDA Drug

• 1 other identifier: BTQ-1901-1902-201
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety (in the eye and throughout the body) and effectiveness of nebivolol (0.5 and 1 percent) and timolol (0.5 percent) eye drop suspensions. These eye drops will be compared to timolol 0.5 percent eye drop solution in participants with open angle glaucoma (the most common type of glaucoma) or high eye pressure (ocular hypertension).

Conditions

Open-Angle Glaucoma; Ocular Hypertension

Outcome Measures

Primary Outcomes (1)

• Intraocular Pressure Over 84 Days

  Measured utilizing a calibrated Goldmann tonometer; two consecutive IOP measurements of each eye will be performed. If the 2 measurements differ by more than 2 mm Hg, a third measurement will be taken. The primary efficacy analysis will be the between-group comparison of the mean IOP values in the study eye at 10AM, 2 hours postdose, and 4PM, at each of the Visit 4/Day 15, Visit 5/Day 42, and Visit 6/Day 84 visits (ie, a total of 9 between-group comparisons). A hierarchical analysis will be conducted to compare each of the investigational products against the comparator, timolol 0.5% ophthalmic solution, as follows: (1) nebivolol 1% ophthalmic suspension, (2) nebivolol 0.5% ophthalmic suspension, and (3) timolol ophthalmic suspension.

  Over 84 days

Secondary Outcomes (2)

• Intraocular Pressure: Change From Baseline in Diurnal IOP at Each Visit

  Day 15: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes; Day 42: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes; Day 84: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes

• Intraocular Pressure: Change From Baseline at All Time Points at Each Visit

  Day 15: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes; Day 42: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes; Day 84: 8 AM ± 30 minutes, 2 hours post-dose ± 30 minutes, 4 PM ± 30 minutes

Study Arms (4)

Nebivolol Ophthalmic Suspension 1 Percent

EXPERIMENTAL

Administered twice daily to both eyes for 84 days (12 weeks)

Drug: Nebivolol Ophthalmic Suspension 1 Percent

Nebivolol Ophthalmic Suspension 0.5 Percent

EXPERIMENTAL

Administered twice daily to both eyes for 84 days (12 weeks)

Drug: Nebivolol Ophthalmic Suspension 0.5 Percent

Timolol Ophthalmic Suspension 0.5 Percent

EXPERIMENTAL

Administered twice daily to both eyes for 84 days (12 weeks)

Drug: Timolol Ophthalmic Suspension 0.5 Percent

Timolol Ophthalmic Solution 0.5 Percent

ACTIVE COMPARATOR

Administered twice daily to both eyes for 84 days (12 weeks)

Drug: Timolol Ophthalmic Solution 0.5 Percent

Interventions

Nebivolol Ophthalmic Suspension 1 Percent DRUG

1 drop instilled into each eye twice daily

Nebivolol Ophthalmic Suspension 1 Percent

Nebivolol Ophthalmic Suspension 0.5 Percent DRUG

1 drop instilled into each eye twice daily

Nebivolol Ophthalmic Suspension 0.5 Percent

Timolol Ophthalmic Suspension 0.5 Percent DRUG

1 drop instilled into each eye twice daily

Timolol Ophthalmic Suspension 0.5 Percent

Timolol Ophthalmic Solution 0.5 Percent DRUG

1 drop instilled into each eye twice daily

Timolol Ophthalmic Solution 0.5 Percent

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to understand and sign an informed consent form prior to any study related procedures.
• Able to administer or have a caregiver accurately administer an eye drop.
• Have POAG or OHT in both eyes that requires therapy for IOP and is adequately controlled, in the opinion of the Investigator, on no more than 2 ocular hypotensive medications (fixed dose combinations count as 2 medications). Subjects with OHT on no ocular hypotensive medication are acceptable. Presence of POAG in one eye and OHT in the fellow eye is acceptable.
• \. Able, in the opinion of the Investigator, to safely discontinue use of ocular hypotensive medications, if applicable, and undergo the appropriate required washout period for ocular hypotensive medications prior to Visit 3/Qualification/Baseline.
• \. At Visit 3/Qualification/Baseline, at least one eye must have unmedicated (post washout) IOP ≥ 22 and ≤ 34 mm Hg at 8:00 AM and ≥ 18 and ≤ 34 mm Hg at 10:00 AM and 4:00 PM in the same eye(s) qualifying at the Visit 3 8:00 AM time point. The IOP must be at least 22 mm Hg at each consecutive measurement at the 8:00 AM time point.
• \. No significant VF (visual field) loss, defined as a mean deviation in either eye greater than - 12 dB or a central point of fixation \< 5 dB in either eye. If the VF performed at or within 90 days prior to Visit 1 does not meet study required parameters, it may be repeated (test should be prior to randomization at Visit 3/Qualification/Baseline).
• \. Best corrected visual acuity (BCVA) of +0.6 logMAR or better in both eyes at Visit 1/Screening and Visit 3/Qualification/Baseline.
• \. Central corneal thickness ≥ 480 and ≤ 600 μm in both eyes. Pachymetry within 90 days prior to Screening is acceptable.
• \. Shaffer gonioscopic grade ≥ 3 (in at least 3 quadrants) in both eyes. Gonioscopy within 90 days prior to randomization is acceptable.
• \. Female subjects must be 1-year postmenopausal, surgically sterilized (total hysterectomy, bilateral oophorectomy or bilateral tubal ligation \> 90 days prior to Visit 1/Screening), or women of childbearing potential with a negative urine pregnancy test at Visit 1/Screening and Visit 3/Qualification/Baseline who are not breastfeeding or planning a pregnancy during the study. Women of childbearing potential must use an acceptable form of contraception throughout the study. Acceptable methods include the use of at least one of the following:
• Intrauterine (IUD) device
• Hormonal contraceptive (oral, injection, patch, implant, ring); subjects must have been on the same hormonal contraceptive for ≥ 90 days prior to Visit 1/Screening
• Double barrier method (spermicide used with either a condom or diaphragm)
• Abstinence

You may not qualify if:

• Ocular
• Intraocular pressure ˃ 34 mm Hg in either eye at Visit 1/Screening, Visit 2/Washout Safety Check, or Visit 3/Qualification/Baseline.
• Other forms of glaucoma in either eye, e.g., congenital glaucoma, closed-angle glaucoma, uveitic glaucoma, pseudoexfoliation or pigment dispersion syndrome, or history of angle closure. Narrow angles treated with peripheral iridotomy are allowed if at least 4 months status post iridotomy.
• Current or recent (within 30 days prior to Visit 1/Screening) clinically significant ocular infection or inflammation, in the opinion of the Investigator, in either eye.
• History of conjunctivitis within 90 days prior to Visit 1/Screening, or history of herpes simplex or herpes zoster in either eye.
• Clinically significant ocular disease, in the opinion of the Investigator, in either eye (including, but not limited to corneal edema, uveitis, severe dry eye, proliferative diabetic retinopathy or macular degeneration) that might interfere with the study, confound study results, or put the subject at increased risk.
• Have a cup-to disc (CD) ratio \> 0.8 at Visit 1/Screening in either eye.
• Intravitreal steroid injections within 6 months prior to Visit 1/Screening. Subconjunctival or subtenon steroid injections within 90 days prior to Visit 1/Screening.
• Use of topical ocular medications within 30 days prior to Visit 1/Screening other than ocular hypotensive medications and medications used as part of an eye examination. Artificial tears may be used during this period provided the use is not required for severe dry eye disease.
• Clinically significant ocular trauma or incisional ocular surgery (including routine cataract surgery) in either eye within 6 months prior to Visit 1/Screening. Glaucoma filtering surgery, or minimally invasive glaucoma surgery within 12 months prior to Visit 1/Screening. Laser surgery for IOP reduction within 6 months prior to Visit 1/Screening. Non-incisional ocular surgery or non-glaucomatous laser treatment within 90 days prior to Visit 1/Screening.
• Refractive surgery in either eye (i.e., radial keratotomy, photorefractive keratectomy \[PRK\], laser-assisted in situ keratomileusis \[LASIK\], corneal cross-linking, limbal relaxing incision) within 6 months prior to Visit 1/Screening.
• Any ocular (e.g., corneal) abnormality preventing accurate assessment of IOP.
• Contact lens wear within 1 week prior to Visit 1/Screening or unwillingness to discontinue wear of contacts lenses prior to and during the study period.
• Aphakia.
• General

Sponsors & Collaborators

• Betaliq, Inc.: lead
• Trial Runners, LLC: collaborator
• Summit Analytical LLC: collaborator

Study Sites (1)

Site 0012

Newport Beach, California, 92663, United States

Location

MeSH Terms

Conditions

Glaucoma, Open-Angle; Ocular Hypertension

Condition Hierarchy (Ancestors)

Glaucoma; Eye Diseases

Results Point of Contact

• Title: Barry Butler
• Organization: BLP Management Group LLC

bbutler@blpmgmt.com

813-766-9539

Study Officials

• Kristin Peterson

  Trial Runners, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study is observer masked. The study medication will be provided in foil pouches contained in identical-appearing boxes. An unmasked staff member not involved in performing study endpoint-related procedures (i.e., IOP measurement) will be responsible for providing dosing instructions, dispensing study medication, and conducting study medication accountability and dosing compliance assessment. The identity of the study medications will be masked to the Investigator and study personnel responsible for study endpoint-related procedures. IOP measurements will be performed by the Investigator/designee who will be masked to the readout of the tonometer, which will be read and entered into the source documentation (whether electronic or paper) by a second staff member once the Investigator/designee reaches the correct applanation effect in the slit lamp.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible participants will be randomized in a 1:1:1:1 ratio to 4 treatment arms: nebivolol 0.5% ophthalmic suspension; nebivolol 1.0% ophthalmic suspension; timolol 0.5% ophthalmic suspension; and timolol 0.5% ophthalmic solution.

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: June 2, 2021
• Study Start: April 15, 2021
• Primary Completion: March 31, 2022
• Study Completion: April 29, 2022
• Last Updated: April 17, 2024
• Results First Posted: April 17, 2024

Record last verified: 2024-04

Locations

US (1)