Safety Study of Latanoprost Slow Release Insert

NCT ID: NCT01180062

Last Updated: 2014-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-01-31

Study Completion Date

2014-06-30

Brief Summary

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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

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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.

Conditions

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Primary Open Angle Glaucoma (POAG) Ocular Hypertension (OHT)

Keywords

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Latanoprost subconjunctival insert

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

Group 1 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 0.5µg Latanoprost.

Group Type ACTIVE_COMPARATOR

Latanoprost

Intervention Type DRUG

Group 1 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 0.5µg Latanoprost.

Group 2 will be given two, low dose Latanoprost SR inserts that contain a combined daily dose of 1.0µg Latanoprost.

Duration of drug release is expected to be 3-6 months.

Group 3 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 2.0µg 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.

Group Type ACTIVE_COMPARATOR

Latanoprost

Intervention Type DRUG

Group 1 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 0.5µg Latanoprost.

Group 2 will be given two, low dose Latanoprost SR inserts that contain a combined daily dose of 1.0µg Latanoprost.

Duration of drug release is expected to be 3-6 months.

Group 3 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 2.0µg Latanoprost.

Arm 2

Intervention Type DRUG

Group 2 will be given two, low dose Latanoprost SR inserts that contain a combined daily dose of 1.0µg 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.

Group Type ACTIVE_COMPARATOR

Latanoprost

Intervention Type DRUG

Group 1 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 0.5µg Latanoprost.

Group 2 will be given two, low dose Latanoprost SR inserts that contain a combined daily dose of 1.0µg Latanoprost.

Duration of drug release is expected to be 3-6 months.

Group 3 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 2.0µg Latanoprost.

Latanoprost SR insert

Intervention Type DRUG

Group 3 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 2.0µg Latanoprost.

Interventions

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Latanoprost

Group 1 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 0.5µg Latanoprost.

Group 2 will be given two, low dose Latanoprost SR inserts that contain a combined daily dose of 1.0µg Latanoprost.

Duration of drug release is expected to be 3-6 months.

Group 3 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 2.0µg Latanoprost.

Intervention Type DRUG

Arm 2

Group 2 will be given two, low dose Latanoprost SR inserts that contain a combined daily dose of 1.0µg Latanoprost.

Intervention Type DRUG

Latanoprost SR insert

Group 3 will be given a single, low dose Latanoprost SR insert that contains a daily dose of 2.0µg Latanoprost.

Intervention Type DRUG

Other Intervention Names

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Xalatan Xalatan Xalatan

Eligibility Criteria

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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.

1. At least 18 years old at time of consent.
2. Diagnosis of primary open-angle glaucoma (including pigmentary or pseudoexfoliative glaucoma patients) or ocular hypertension in 1 or both eyes.
3. IOP deemed as well controlled by investigators, with prostaglandin analogue/ prostanoid either as a monotherapy or part of dual medical therapy.
4. Subjects with mild or moderate glaucoma where subjects can be without IOP lowering treatment for up to 2 months.
5. 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).
6. 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.
7. Best Corrected Visual Acuity of 20/100 or better by Snellen's visual acuity measurement in each eye (or equivalent ETDRS Visual acuity).
8. Clear ocular media with good view of optic disc and macula.
9. Negative urine pregnancy test at baseline for women of childbearing potential.
10. An informed consent document signed and dated by the subject or a legally acceptable representative.
11. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria

1. 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.
2. Subjects with diagnosis of secondary glaucoma.
3. Diagnosis of a clinically significant or progressive retinal disease (e.g. diabetic retinopathy, macular degeneration) in either eye that would inhibit accurate VA testing.
4. Advanced glaucoma defined by a cup/disc ratio \>0.8 or a history of severe central visual field loss in either eye.
5. History of intolerance and or lack of response to prostaglandin analogues.
6. History of hypersensitivity to latanoprost or any other ingredient in the study drug.
7. Central corneal thickness greater than 600 μm in either eye.
8. Any condition that prevents reliable applanation tonometry (e.g. significant abnormalities of the corneal surface) in either eye.
9. History of severe dry eye.
10. Eye lid abnormalities i.e. entropion, ectropion or lower lid retraction.
11. Evidence of corneal punctate staining, exposure keratopathy or keratitis, history of infectious keratitis i.e. herpes.
12. History of ocular cicatricial diseases i.e. cicatricial pemphigoid, pemphigus, S-J syndrome, conjunctival scarring secondary to topical medications.
13. History of endothelial dystrophy (Fuchs, corneal guttata) or corneal edema.
14. History of iritis or uveitis.
15. History of clinically significant aspirin intolerant asthma (AIA).
16. History of any ocular surgery or trauma in either eye within 3 months of the screening visit.
17. History of glaucoma filtration surgery including but not limited to Trabeculectomy, Canaloplasty, Trabectome and Glaucoma Drain surgery.
18. History of ocular infection, ocular inflammation, or laser surgery in either eye within 3 months of the screening visit.
19. Unable to discontinue contact lens use.
20. Anticipate the need to initiate or modify medication (systemic or topical) that is known to affect IOP during the study period.
21. Any severe acute or chronic medical or psychiatric condition that could increase the risk associated with study participation or could interfere with the interpretation of study results and, in the judgment of the investigator, could make the patient inappropriate for entry into this study.
22. Treatment with an investigational drug or device within 30 days preceding the device placement.
23. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of nonhormonal contraception as outlined in this protocol from at least 14 days prior to the first dose of study medication and throughout the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Daniel Moore

OTHER

Sponsor Role lead

Responsible Party

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Daniel Moore

Sponsor/PI

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Daniel B. Moore, M.D.

Role: PRINCIPAL_INVESTIGATOR

Univ of Kentucky

Locations

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Univ of Ky Dept of Ophthalmology and Visual Sciences

Lexington, Kentucky, United States

Site Status

Countries

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United States

Other Identifiers

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IND# 109,182

Identifier Type: OTHER

Identifier Source: secondary_id

10-0476-F1V

Identifier Type: -

Identifier Source: org_study_id