Abstract
Purpose :
Meibomian gland dysfunction (MGD) is the root cause of many downstream ocular surface symptoms with no FDA-approved medications available. AZR-MD-001 is being developed for the treatment and management of the symptoms of MGD. The purpose of these pre-clinical studies was to evaluate the toxicology profile of AZR-MD-001 in repeat dose toxicology studies in rabbits and dogs.
Methods :
In pivotal repeat dose toxicology studies, conducted per Good Laboratory Practice (GLP) regulations, animals (Dutch Belted rabbits for 6 months and beagle dogs for 3 months, both with a 4-week recovery period) were treated with vehicle daily (QD) or AZR-MD-001 at concentration of 1% or 2.5%, either twice weekly (2.5%) or QD (1% and 2.5%). Test article or vehicle control was applied along the lower eyelid margin of both eyes. Measurements included general health observations, body weight, electrocardiography (ECG; dogs only), ocular assessment of both eyes by tolerability scale, Dermal Draize, Ocular Draize and intraocular pressure. Ophthalmic examinations were performed by Board Certified Veterinary Ophthalmologist including slit-lamp biomicroscopy with modified McDonald-Shadduck scoring, fluorescein staining, eyelid evaluation, and indirect ophthalmoscopy. Blood was collected for toxicokinetic (TK) analysis and clinical pathology. On necropsy all organs were weighed. The eyes, ocular adnexa, and nasal turbinates were sent for a histopathological evaluation.
Results :
No ocular or eyelid pathologies were observed by macroscopic observations or slit-lamp examinations. No systemic effects were found by clinical observations, body weight, ECG (dogs), clinical pathology, and organ weights. TK analyses demonstrated no effect on endogenous plasma selenium levels. No test article-related macroscopic or microscopic findings were observed in animals at scheduled necropsy. No sex-differences were noted.
Conclusions :
These findings demonstrated that AZR–MD–001, up to 2.5%, QD in both eyes was well tolerated both ocularly and systemically in test animals. The nonclinical toxicology program supported the clinical Phase 2 program and supports continuing to Phase 3 studies evaluating the safety and efficacy of AZR–MD–001 up to a concentration of 1.0% dosed twice a week in humans.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.