Effect of Topical Naltrexone Ophthalmic Solution on the Signs and Symptoms of Dry Eye in Diabetic Subjects

This is a Phase 2, single-center, double-masked, randomized, placebo-controlled study to compare the safety and efficacy of Naltrexone Ophthalmic Solution, 0.002% to placebo for the treatment of the signs and symptoms of dry eye in diabetic subjects. Subjects eligible to be randomized will receive one of the following treatments to be administered bilaterally BID for 29 days (from Visit 2 to Visit 5): Naltrexone Ophthalmic Solution, 0.002% or Placebo Ophthalmic Solution (Vehicle). During a 10-day study run-in period (for the purpose of subject selection) prior to randomization, all subjects will receive Placebo Ophthalmic Solution (Vehicle) bilaterally BID. Participants who terminate early during the application period will be asked to complete safety assessments (if the participants agree) prior to study exit. Participants who are terminated early from the study will not be replaced.

Inclusion criteria

• Provide written informed consent;
• Have a diagnosis of type 1 or type 2 diabetes mellitus prior to Visit 1;
• Have a reported history of dry eye for at least 6 months prior to Visit 1;
• Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1;
• Have a corneal fluorescein staining score of ≥ 2 in any region (inferior, superior, or central regions) in at least one eye at Visits 1 and 2 (must be the same eye at Visits 1 and 2);
• Have at least one of the following at Visits 1 and 2:

• A total lissamine green conjunctival score of ≥ 2 in at least one eye, based on the sum of the temporal and nasal regions at Visits 1 and 2 (must be the same eye at Visits 1 and 2);
• Report an OSDI score ≥ 20 at Visits 1 and 2.

Exclusion criteria

• Have any clinically significant slit lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction (MGD), lid margin inflammation or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters;
• Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1;
• Have concurrent neurotrophic keratopathy from a source other than diabetes (h/o HSV keratitis, h/o HZO with ocular manifestations, or CN VII palsy or other condition resulting in lagophthalmos);
• Have active diabetic foot ulcers;
• Have a corneal sensitivity score ≤ 1.5 cm as measured by Cochet-Bonnet at Visit 1;
• Report an OSDI score > 75 at Visits 1 and 2;
• Have worn contact lenses within 21 days of Visit 1 or anticipate using contact lenses during the study (no contact lens wear during study);
• Have used any eye drops within 2 hours of Visit 1;
• Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 24 months;
• Have used cyclosporine 0.05% or lifitigrast 5.0% ophthalmic solution within 45 days of Visit 1;
• Have any planned ocular and/or lid surgeries over the study period or any ocular surgery within the last 12 months;
• Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit 1;
• Be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter (OTC) solutions, artificial tears, gels or scrubs, and cannot discontinue these medications for the duration of the trial (excluding medications allowed for the conduct of the study);
• Have corrected visual acuity greater than or equal to logMAR +0.7 as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) scale in either eye at Visit 1;
• Have concurrent autoimmune disease causing dry eye (e.g., rheumatoid arthritis, Sjogren's, GVHD, Steven's Johnson, Grave's);
• Have Fuchs endothelial dystrophy;
• Have recurrent corneal erosion syndrome or anterior basement membrane dystrophy;
• Be a woman who is pregnant, nursing, or planning a pregnancy;
• Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 5 (or early termination visit) if of childbearing potential. Non-childbearing potential is defined as a woman who is permanently sterilized (i.e., has had a hysterectomy or bilateral tubal ligation), or is post-menopausal (without menses for 12 consecutive months);
• Be a woman of childbearing potential who is not using an acceptable means of birth control; acceptable methods of contraception include: hormonal - oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as a diaphragm or condom; IUD; or surgical sterilization of partner. For non-sexually active females, abstinence may be regarded as an adequate method of birth control; however, if the subject becomes sexually active during the study, they must agree to use adequate birth control as defined above for the remainder of the study;
• Have a known allergy and/or sensitivity to the test article or its components;
• Have a condition or be in a situation which the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study;
• Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days of Visit 1;
• Be currently using any medication known to cause ocular drying that is not used on a stable dosing regimen for at least 30 days prior to Visit 1;
• Be unable or unwilling to follow instructions, including participation in all study assessments and visits.
• Be currently using a systemic opioid antagonist (e.g., Naltrexone or Naloxone) or have used a systemic opioid antagonist in the previous 90 days