Phase 3 Study of the Safety and Efficacy of OmegaD Softgels in the Treatment of Dry Eye Disease

A Randomized, Multicenter, Double-Masked, Placebo Controlled Study of the Safety and Efficacy of OmegaD Softgels in the Treatment of Dry Eye Disease

This is a phase 3 study to evaluate the safety and efficacy of OmegaD softgels for the treatment of dry eye disease. A daily dose of 2 OmegaD softgels dosed orally BID will be compared to 2 placebo softgels (mineral oil ) dosed orally BID for 84 days. Approximately 300 subjects will be evaluated for their signs and symptoms of dry eye disease and for safety throughout the study.

Inflammation is a key component of dry eye disease. Increasing the systemic levels of omega-3 fatty acids relative to omega-6 levels can mediate immune responses. Evaluating whether omega-3 supplementation can improve dry eye disease signs, symptoms and associated measures of inflammation may present a new therapeutic option for dry eye disease.

The primary objective of this study is to evaluate the safety and efficacy of twice daily (BID) dosing of OmegaD softgels in subjects with dry eye disease.

Male and female subjects between 18 years and 90 years of age, with at least moderate ocular surface disease (OSDI ≥ 20) dry eye symptoms and a clinical diagnosis of dry eye disease supported by global clinical assessment will be screened and enrolled. Each subject must have, in at least one eye, tear osmolarity of ≥ 312 mOsm/L and meibomian gland dysfunction as defined by a grade of 1 or 2 on the meibomian orifice size scale at both Screening and Baseline in at least one eye. In addition, Tear break up time (TBUT) must be ≤ 7 seconds in both eyes at Screening and the Schirmer's test score in both eye(s) must be ≥ 5 mm at Screening.

Approximately 300 subjects will be randomized (1:1) to 1 of 2 treatment arms and treated for 84 days (12 weeks) with either OmegaD softgels; 2 softgels BID or placebo softgels; 2 softgels BID. The study will be double-masked with OmegaD and placebo being identical-appearing softgels.

Subjects will participate in safety and efficacy assessments throughout the study. Efficacy assessments will include, tear osmolarity, meibomian gland dysfunction grading, TBUT, Schirmer's Test, and dry eye symptoms based on the OSDI questionnaire, Safety assessments will include, slit lamp examination and adverse events.

Inclusion Criteria:

1. Subjects age ≥ 18 years and ≤ 90 years on the date of informed consent.
2. All subjects must provide signed written consent prior to participation in any study-related procedures.
3. At least moderate ocular surface disease as measured by an OSDI score ≥ 20 at Screening.
4. Clinical diagnosis of dry eye disease supported by global clinical assessment.
5. Presence of tear osmolarity in at least one eye ≥ 312 mOsm/L at both Screening and Baseline.
6. Schirmer's test score (anesthetized) ≥ 5 mm in both eyes at Screening.
7. TBUT ≤ 7 seconds in both eyes at Screening.
8. Presence of meibomian gland dysfunction as defined by a grade of 1 or 2 on the meibomian orifice size scale in at least one eye at both Screening and Baseline. The qualifying osmolarity level and meibomian orifice size grade must be present in the same eye at both Screening and Baseline if only one eye qualifies.

Exclusion Criteria:

1. Any previous reconstructive or cosmetic eyelid surgery that may, in the Investigator's opinion, affect the normal function of the lids (eg, blepharoplasty, ptosis repair, entropion/ectropion repair) that could affect study parameters/assessments.

2. Cataract extraction, with or without minimally invasive glaucoma surgery (eg, iStent), within 90 days prior to Screening.

3. Any previous invasive glaucoma surgery (eg, trabeculectomy, shunts, valves) and/or corneal surgery (eg, penetrating keratoplasty, lamellar keratoplasty, Descemet's stripping endothelial keratoplasty [DSEK]).

4. Lid scrubs with over-the-counter (OTC) products (eg, OCuSOFT lid scrub, SteriLid, baby shampoo, etc.) and/or warm compresses within 14 days prior to Screening and throughout the study period.

5. Prescription and OTC ophthalmic mast cell stabilizers and antihistamines within 21 days prior to Screening and throughout the study period (systemic mast cell stabilizers are allowed, and systemic antihistamines are permitted with certain restrictions [see exclusion criterion 16]).

6. Chronic daily use (defined as > 7 consecutive days at the recommended dosing frequency) of systemic narcotics for any chronic pain syndrome (eg, fibromyalgia, rheumatoid arthritis, etc.) during the study period. Short-term, as-needed dosing of a systemic narcotic for ≤ 72 hours is allowed, but not at Screening or on the day of the study visit.

7. Allergy to fish oil or mineral oil (component of placebo softgels) or any component of the softgel material.

8. Clinically significant eyelid deformity or eyelid movement disorder that is caused by conditions such as notch deformity, incomplete lid closure, entropion, ectropion, hordeolum, or chalazion.

9. Active or anticipated seasonal and/or perennial allergic conjunctivitis or rhinitis.

10. Previous ocular disease leaving sequelae or requiring current topical eye therapy other than for dry eye disease, including, but not limited to, active corneal or conjunctival infection or inflammation of the eye and ocular surface scarring.

11. History or presence of abnormal nasolacrimal drainage.

12. Laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) performed within one year prior to Screening and throughout the study period.

13. Ophthalmic artificial tear drop use within 2 hours prior to any study visit. Any OTC artificial tear (preserved or unpreserved) should be continued at the same frequency and with no change in drop brand.

14. Contact lens wear within 12 hours prior to Screening or any study visit; subjects determined to have worn contact lenses within 12 hours must be rescheduled.

15. History of cauterization of the punctum or existing silicone punctal plug(s); history of silicone plug removal or collagen plug insertion or removal within 12 months prior to Screening and throughout the study period.

16. Started or changed the dose of systemic medications known to affect tear production within 30 days prior to Screening and throughout the study period. Short-term, as-needed dosing of a systemic medication is allowed with certain restrictions. One 7-day course of systemic antihistamines is allowed, but not within 7 days of Screening or any other study visit. One short (≤ 72 hour) course of the other systemic medications that affect tear production is allowed but not within 30 days of Screening or on the day of any other study visit. These include, but are not limited to, the following medications:

    • Immunomodulators
    • Tricyclic antidepressants
    • Diuretics
    • Corticosteroids (intranasal, inhaled, topical dermatological, and perianal steroids are permitted)

17. Use of any topical prescription ophthalmic medications (including cyclosporine [Restasis®, Cequa®] or topical lifitegrast [Xiidra®], steroids, nonsteroidal anti-inflammatory drugs [NSAIDs], anti-glaucoma medications, anti-microbials), topical macrolides, or oral nutraceuticals (fish, flax, black currant seed oils, etc.) within 21 days prior to Screening and throughout the study period.

18. Use of oral tetracyclines or oral macrolides within 21 days prior to Screening and throughout the study period; use of isotretinoin (Accutane®) within 90 days prior to Screening and throughout the study period.

19. Chronic daily use (defined as > 7 consecutive days at the recommended dosing frequency) of oral NSAIDs during the study period. ANY use of oral NSAIDs during the study period must be discussed with the Medical Monitor. Aspirin of any dosage is permitted.

20. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Acceptable methods include the use of at least one of the following: intrauterine device (IUD), hormonal (oral, injection, patch, implant, ring), barrier with spermicide (condom, diaphragm), or abstinence. An adult woman is considered to be of childbearing potential unless she is 1 year postmenopausal or postsurgical hysterectomy. All women of childbearing potential, including those post-tubal ligation, must have a negative urine pregnancy test result at Visit 1 (Screening), Visit 2 (Baseline), and Visit 4 (Day 84) examinations and must intend to not become pregnant during the study.

21. Participation in any drug or device clinical investigation within 30 days prior to entry into this study and/or during the period of study participation.