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

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 tes