PURPOSE:To determine the efficacy and safety of AZR-MD-001 (0.5 % and 1.0 %) ophthalmic ointment, relative to vehicle, over 3-6 months of treatment, in participants with meibomian gland dysfunction (MGD). METHODS:This was a Phase 2, randomized, vehicle-controlled, multicenter extension clinical trial. Eligible participants were adults with MGD (meibomian gland secretion score (MGS) ≤12 out of 15 glands) who discontinued all other dry eye or MGD treatments. Participants were randomized 1:1:1 to apply AZR-MD-001 1.0 %, 0.5 %, or vehicle to the lower eyelids, twice weekly. Key exploratory endpoints included the least-squared mean difference between groups in the change from baseline in clinical signs (meibomian gland yielding score; MGYLS) and symptoms (Ocular Surface Disease Index; OSDI), at clinic visits at Month 4.5 and 6, and safety measures from 36 months. RESULTS:Participants (66.5 % female) were randomized, at baseline, to AZR-MD-001 0.5 % (n = 82), 1.0 % (n = 83), or vehicle (n = 80). Statistically significant improvements, compared to vehicle, were observed at Month 6 in MGYLS for both AZR-MD-001 groups (0.5 % group: 1.9, 95 % CI 0.9 to 2.8, P = 0.002; 1.0 % group: 1.1, 95 % CI 0.2 to 2.1, P = 0.026), and in OSDI score for the 0.5 % group (-4.5, 95 % CI -8.0 to -0.9, P = 0.0135). The most common adverse events for AZR-MD-001 were application site pain, superficial punctate keratitis and eye pain; most were mild to moderate in severity, and decreased in incidence over time. CONCLUSIONS:AZR-MD-001 (0.5 %) was efficacious in treating signs and symptoms of MGD over six months, with a lower observed incidence of new adverse events over time.

BACKGROUND:Contact lens discomfort (CLD) is a common problem for CL wearers, and patients with CLD often have changes in meibomian gland function and structure. In a Phase 2 trial AZR-MD-001 0.5% (AZR) ophthalmic ointment improved meibomian gland dysfunction (MGD) in non-lens wearers. The current study evaluated the efficacy and safety of AZR in participants with CLD and concomitant MGD. METHODS:Adults with CLD (Contact Lens Dry Eye Questionnaire-8 >12, range 0-37) and MGD (Meibomian Gland Secretion Score [MGS] ≤12, range 0-45) were randomized (1:1) to AZR:vehicle applied twice-weekly in a three-month multicenter, prospective, double-masked study. Endpoints included difference in change from baseline (CFB) in the number of Meibomian Glands Yielding Liquid Secretion (MGYLS), MGS, the ability to wear their lenses as long as desired, and safety. RESULTS:At Month 3, AZR (n = 34) significantly increased the MGYLS and MGS versus vehicle (n = 33), with least squares mean difference (LSMD) CFB in MGYLS of 5.0 (SE = 0.47) for AZR and 1.6 (0.45) for vehicle, P < 0.0001; MGS of 13.8 (SE = 0.67) for AZR and 3.8 (SE = 0.68) for vehicle, P < 0.0001. Significantly more participants treated with AZR were able to wear lenses as long as desired (43% vs. 6%, P = 0.0023). The most common treatment-emergent adverse event (TEAE) was eye irritation (61.8% AZR; 0% vehicle). All TEAEs related to treatment were mild/moderate, transient, and did not result in discontinuation. CONCLUSION:AZR-MD-001 0.5% significantly improved MGD signs and hours of comfortable CL wear, demonstrating good efficacy, safety, and tolerability in those with CLD.

PURPOSE:Meibomian gland dysfunction (MGD) is a chronic progressive disease with downstream effects on ocular signs and symptoms. AZR-MD-001 is a selenium sulfide ophthalmic ointment that was investigated as a potential treatment option for patients with MGD. METHODS:A Phase 2, multi-center, double-masked, parallel group study was conducted across 29 sites, with 245 patients randomized 1:1:1 to AZR-MD-001 0.5%, AZR-MD-001 1.0% or vehicle applied to the lower eyelid, twice weekly. Patients were eligible for the trial if they presented with signs and symptoms of MGD. Co-primary efficacy endpoints were the changes from baseline in number of open glands (Meibomian Glands Yielding Liquid Secretion [MGYLS] score) and patient-reported ocular surface symptoms (Ocular Surface Disease Index [OSDI] total score) at Month 3. Efficacy outcomes were captured at Day 14, Month 1.5 and Month 3. Safety and tolerability were assessed for treatment-emergent adverse events (TEAEs). RESULTS:AZR-MD-001 0.5% (n = 82 patients) treatment resulted in significant improvements in MGYLS score, with patients experiencing an average increase from baseline of 4.2 and 2.4 open glands secreting meibum for the drug and vehicle, respectively (p < 0.001) and from baseline a mean OSDI total score improvement of 7.3 and 3.8 for the drug and vehicle, respectively (p < 0.05). Most TEAEs were mild and transient, with 3 serious adverse events (SAEs) reported with AZR-MD-001 (none related to study drug). CONCLUSIONS:Co-primary endpoints were met for AZR-MD-001 0.5% at Month 3, with a statistically significant improvement in the signs and symptoms of MGD. AZR-MD-001 was safe and well tolerated. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03652051, ANZCTR Registration Number: AZ201801.