Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3

Inclusion Criteria: * Be at least 18 years of age; * Provide written informed consent; * Have a subject reported history of dry eye prior to Visit 1; * Have a history of use or desire to use eye drops for dry eye symptoms 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 worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the 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 6 months; * Have used Restasis®, Xiidra® Cequa®, or TrueTear® within 45 days of Visit 1 or Lipiflow® within 6 months of Visit 1; * Have an intraocular pressure (IOP) \> 25 mmHg at Visit 1; * Have any planned ocular and/or lid surgeries over the study period; * 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 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 logarithm of the minimum angle of resolution (logMAR) +0.7 as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) scale in both eyes at Visit 1; * Have an uncontrolled systemic disease; * Be a woman who is pregnant, nursing or planning a pregnancy; * Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 4 (or early termination visit) if of childbearing potential. Non-childbearing potential is defined as a woman who is permanently sterilized (e.g., has had a hysterectomy or bilateral tubal ligation or bilateral oophorectomy), 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; intrauterine device (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, she 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 study drug 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; * Have used an investigational drug or device within 30 days of Visit 1; * Be currently using any medication known to cause ocular drying (e.g., antihistamines, anti-depressants) or increased lacrimation (e.g., cholinergics) that is not used on a stable dosing regimen for at least 30 days prior to Visit 1; * Be receiving systemic corticosteroid therapy (not including inhaled corticosteroids), ophthalmic topical steroids, topical nonsteroidal antiinflammatory drugs (NSAIDs), topical antibiotics, immunotherapy, or cytotoxic therapy within 14 days of Visit 1 or anticipate such therapy throughout the study period. * Be unable or unwilling to follow instructions, including participation in all study assessments and visits.