A Phase 1, Open-label, Dose Escalation Study to Evaluate the Safety and Tolerability of Latanoprost Sustained Release (SR) Insert in Patients With Primary Open Angle Glaucoma (POAG) or Ocular Hypertension (OHT)
Overview
- Phase
- Phase 1
- Intervention
- Latanoprost
- Conditions
- Primary Open Angle Glaucoma (POAG)
- Sponsor
- Daniel Moore
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Intraocular Pressure
- Status
- Terminated
- Last Updated
- 11 years ago
Overview
Brief Summary
This study is a phase 1, open-label, dose-escalation, safety and tolerability study, which will be conducted at one study site. This study will include 3 cohorts. Each cohort will have approximately 5 subjects. Subjects will not be randomized into the study. The first cohort will receive low dose drug insert, second cohort will receive 2 low dose drug inserts thus achieving twice the drug levels compared to cohort I and third cohort will receive high dose drug insert.
Detailed Description
The purpose of this study is to determine the tolerability and safety of the biodegradable extended release Latanoprost subconjunctival insert for primary open angle glaucoma (POAG) and ocular hypertension (OHT) patients. Intraocular pressure lowering ability of biodegradable extended release Latanoprost subconjunctival insert in POAG and OHT patients will also be evaluated. Low dose inserts have an initial release rate of approximately 1 µg/day slowing to 0.2 µg/day after approximately 10 days; this release rate is maintained. High dose inserts have an initial release of approximately 4 µg/day, which slows to approximately 1 ug/day after 10 days. Each drop of Xalatan (the commercial form of latanoprost) contains approximately 1 µg of latanoprost. The first cohort will receive inserts that initially provide the same dose as is administered topically before their release rate slows down to a lower dose. The inserts used in this study are composed of a drug core in a (Poly Lactic Glycolic acid) PLGA polymer tube. One end of the tube is capped with an impermeable polymer (silicone) and the other end with a permeable polymer (Polyvinyl alcohol). Drug release occurs across the permeable end and is a function of internal diameter of the tube. Low dose insert and high dose insert are exactly the same except that for low dose inserts the internal diameter of the PLGA tubes is smaller. Thus different release rates (and drug loading) are obtained with the same formulation. Inserts are designed to provide steady state release for 3-6 months.
Investigators
Daniel Moore
Sponsor/PI
University of Kentucky
Eligibility Criteria
Inclusion Criteria
- •Male and female POAG and OHT subjects who are well controlled on mono therapy or dual therapy, who have not undergone any prior glaucoma surgeries and are not allergic or non-responders to any prostaglandin analogues, will be included in this study.
- •At least 18 years old at time of consent.
- •Diagnosis of primary open-angle glaucoma (including pigmentary or pseudoexfoliative glaucoma patients) or ocular hypertension in 1 or both eyes.
- •IOP deemed as well controlled by investigators, with prostaglandin analogue/ prostanoid either as a monotherapy or part of dual medical therapy.
- •Subjects with mild or moderate glaucoma where subjects can be without IOP lowering treatment for up to 2 months.
- •Mean IOP of at least 22 mmHg in the study eye and not more than 36 mmHg in either eye at 8 AM on the baseline visit (after 4 weeks of washout).
- •Mean IOP of at least 20 mmHg in the same eye that qualified at 8 AM and not more than 36 mmHg in either eye at 10 AM, 12 PM, 2 PM and 4 PM on baseline visit.
- •Best Corrected Visual Acuity of 20/100 or better by Snellen's visual acuity measurement in each eye (or equivalent ETDRS Visual acuity).
- •Clear ocular media with good view of optic disc and macula.
- •Negative urine pregnancy test at baseline for women of childbearing potential.
Exclusion Criteria
- •Closed/barely open anterior chamber angle or a history of acute angle closure (i.e., 75% of the circumference of the angle is 10° or less) in either eye.
- •Subjects with diagnosis of secondary glaucoma.
- •Diagnosis of a clinically significant or progressive retinal disease (e.g. diabetic retinopathy, macular degeneration) in either eye that would inhibit accurate VA testing.
- •Advanced glaucoma defined by a cup/disc ratio \>0.8 or a history of severe central visual field loss in either eye.
- •History of intolerance and or lack of response to prostaglandin analogues.
- •History of hypersensitivity to latanoprost or any other ingredient in the study drug.
- •Central corneal thickness greater than 600 μm in either eye.
- •Any condition that prevents reliable applanation tonometry (e.g. significant abnormalities of the corneal surface) in either eye.
- •History of severe dry eye.
- •Eye lid abnormalities i.e. entropion, ectropion or lower lid retraction.
Arms & Interventions
Arm 1
Group 1 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 0.5µg Latanoprost.
Intervention: Latanoprost
Active Comparator - Arm 2
Group 2 will be given two, low dose Latanoprost SR inserts that contain a combined daily dose of 1.0µg Latanoprost.
Intervention: Latanoprost
Active Comparator - Arm 2
Group 2 will be given two, low dose Latanoprost SR inserts that contain a combined daily dose of 1.0µg Latanoprost.
Intervention: Arm 2
Active Comparator - Arm 3
Group 3 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 2.0µg Latanoprost.
Intervention: Latanoprost
Active Comparator - Arm 3
Group 3 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 2.0µg Latanoprost.
Intervention: Latanoprost SR insert
Outcomes
Primary Outcomes
Intraocular Pressure
Time Frame: 12 months
1. Local reaction around the insert site including swelling, hyperemia, scarring, erosion, infection in the study eye 2. Hyperemia grading for both eyes 3. Discomfort and tolerability scale 4. Occurrence of iritis/uveitis in the study eye 5. Detection of macular thickening/edema in the study eye
Secondary Outcomes
- Intraocular pressure parameters i.e. mean IOP, IOP range, percentage reduction in IOP, IOP fluctuation.(12 months)