AR-12286 in Combination With Latanoprost

Condition(s) targeted: Glaucoma; Ocular Hypertension

Intervention: Latanoprost 0.005% (Drug); AR-12286 Ophthalmic Solution 0.5% (Drug); Timolol maleate ophthalmic solution 0.5% (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Aerie Pharmaceuticals

This is a double-masked, randomized, multi-center, active-controlled, crossover comparison of the addition of AR-12286 or timolol to latanoprost in the treatment of elevated intraocular pressure (IOP).

Official title: A Phase 2, Double-masked, Randomized, Active-controlled, Crossover Study Assessing the Safety and Ocular Hypotensive Efficacy of AR-12286 or Timolol Added to Patients With Elevated Intraocular Pressure Currently Using Latanoprost

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Intraocular pressure

Secondary outcome:

Ocular safety

Systemic safety

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 18 years of age or greater.

- Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT).

- Currently using prostaglandin analogue (monotherapy or combination therapy) O. U. ≥ 1

month at time of study entry (first qualification visit) in study eye(s).

- Qualification Visit 1 (Screening) IOP at 16: 00 hrs: PG monotherapy patients: ≥ 18 mm

Hg; Combination therapy patients: >= 16 mm Hg. Qualification Visit 2 (post latanoprost run-in) IOP ≥ 20 mm Hg at 08: 00 hrs and 10: 00 hrs, IOP ≥ 18 mm Hg at 16: 00 hrs in study eye(s). (Note: combination therapy may include any combination of topical ocular hypotensive agents).

- Corrected visual acuity in each eye +1. 0 logMAR or better by ETDRS in each eye

(equivalent to 20/200).

- Able and willing to give signed informed consent and follow study instructions

Exclusion Criteria: In either eye:

- Previously randomized to treatment in a clinical study of AR-12286.

- Intraocular pressure > 36 mm Hg.

- History of acute angle-closure glaucoma, or closed or narrow angle upon gonioscopy

- Known hypersensitivity or contraindication to timolol maleate ophthalmic solution, or

any component of the formulation (benzalkonium chloride, etc.), or to topical anesthetics, including history of conjunctival hyperemia with topical latanoprost of severity greater than 1 on a 0-3 scale.

- Ocular trauma within the past six months, or ocular surgery or laser treatment within

the past three months.

- Contact lens wear within 30 minutes of instillation of study medication.

- PG monotherapy patients: Ocular hypotensive medication (other than prostaglandin)

within 4 weeks of Visit 0 (Study entry, first qualification visit). Combination therapy patients: Ocular hypotensive medication (other than prostaglandin and current additional agent) within 4 weeks of Visit 0 (Study entry, first qualification visit).

- Conjunctival hyperemia of grade 2+ or greater at Visit 1.

- Any other ocular medication within 4 weeks of Visit 1 with the exception of

lubricating drops for dry eye (which may be used throughout the study).

- Clinically significant ocular disease (e. g. corneal edema, uveitis, severe

keratoconjunctivitis sicca) which might interfere with the study, including glaucomatous damage so severe that treatment with only latanoprost for two periods of up to 4 weeks is not judged safe (e. g., advanced glaucomatous optic nerve head or visual field loss).

- Any abnormality preventing reliable applanation tonometry of either eye.

In study eye(s):

- Glaucoma: pseudoexfoliation or pigment dispersion component, history of angle

closure. Note: Previous laser peripheral iridotomy is acceptable.

- Previous glaucoma intraocular surgery or laser procedures.

- Refractive surgery (e. g., radial keratotomy, PRK, LASIK, etc.).

- Central corneal thickness greater than 600 µ.

Systemic:

- Known bronchial asthma (history or current), severe chronic obstructive pulmonary

disease, sinus bradycardia, second or third degree atrioventricular block or overt cardiac failure.

- Clinically significant abnormalities in laboratory tests at screening, recognizing

that subjects are not fasting at the time of drawing blood.

- Clinically significant systemic disease (e. g., uncontrolled diabetes, myasthenia

gravis, hepatic, renal, cardiovascular or endocrine disorders) which might interfere with the study.

- Participation in any investigational study within the past 30 days.

- Changes of systemic medication that could have a substantial effect on IOP 4 weeks

prior to screening, or anticipated during the study.

- Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or

not using a medically acceptable form of birth control.

David Silverstone, M.D., New Haven, Connecticut 06510, United States

Coastal Research Associates, LLC, Roswell, Georgia 30076, United States

Heart of America Eye Care, P.A., Shawnee Mission, Kansas 66204, United States

Taustine Eye Center, Louisville, Kentucky 40217, United States

Alan L Robin, M.D., Baltimore, Maryland 21209, United States

Comprehensive Eye Care, St Louis, Missouri 63090, United States

Rochester Ophthalmology Group, Rochester, New York 14618, United States

Glaucoma Consultants of the Capital Region, Slingerlands, New York 12159, United States

Charlotte Eye Ear Nose and Throat, Charlotte, North Carolina 28210, United States

Thomas K. Mundorf, M.D., Charlotte, North Carolina 28204, United States

The Eye Institute, Tulsa, Oklahoma 74104, United States

Wills Eye Hospital, Philadelphia, Pennsylvania 19107, United States

Black Hills Regional Eye Institute, Rapid City, South Dakota 57701, United States

Cataract & Glaucoma Center, El Paso, Texas 79902, United States

Stacy R. Smith, M.D., Salt Lake City, Utah 84117, United States

Starting date: February 2011
Last updated: April 18, 2014