Effect of Topical Naltrexone Ophthalmic Solution on the Signs and Symptoms of Dry Eye in Diabetic Subjects
Condition: Dry Eye Disease
MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases
Intervention: Naltrexone; Placebos
Intervention description: naltrexone formulated as ophthalmic solution; Placebo ophthalmic solution
Intervention MeSH terms: Naltrexone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: naltrexone; dry eye; diabetic subjects

Summary:

      The objective of this exploratory study is to determine the safety and efficacy of 0.002%
      Naltrexone Ophthalmic Solution, compared to placebo for the treatment of the signs and
      symptoms of dry eye in diabetic subjects.
    

Eligibility criteria:

        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:

               1. 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);

               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