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Arthur Driscoll, Charles D Blizzard, Michael Bassett, Monica OConnor, Steve Takach, Doug Molla, Peter K Jarrett, Amarpreet Sawhney; 90 Day Canine Toxicity Study Demonstrating the Safety of a Sustained Release Travoprost Punctum Plug. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4885.
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To evaluate the potential ocular toxicity and irritation, and systemic toxicity of the Travoprost Punctum Plug (OTX-TP1) after repeat insertion every 30 days over a 90 day period in beagles and the reversibility, persistence, and delayed occurrence of any toxic effects after a 14 day recovery period.
The study conduct was in accordance with FDA 21 CFR, Part 58 GLP for Non Clinical Laboratory Studies. Baseline ophthalmic exams and clinical pathology were conducted prior to study dosing. OTX-TP1 was inserted into the vertical canaliculus in one eye of 16 male and female beagles; the contralateral eye received no treatment. A control group of 16 canines received a sham insertion procedure in one eye and the contralateral eye received a placebo vehicle punctum plug. At 30 and 60 days, punctum plugs were removed and new plugs inserted. Ophthalmic examinations were performed throughout the study and included slit lamp biomicroscopy, fluorescein staining, fundoscopy, and tonometry. Plasma and tear fluid were collected during the study. Daily general clinical observations were recorded; body weight and food consumption were recorded weekly. Canines were sacrificed at Day 91 or Day 105 (14 day recovery period) and clinical pathology and complete necropsies conducted. Histology was assessed on all ocular tissues and nasal turbinates.
The punctum plugs were well tolerated overall (Table 1). Punctum plug retention was high, with plugs present in 97% of assessments. Macroscopic and microscopic assessments exhibited no test article related toxicity findings. Ophthalmic observations were limited and indicated only slight irritation; observations were minor in nature, therefore were not considered adverse. Test articles demonstrated no effect on clinical pathology, body weights, or food consumption. Sustained local drug release of travoprost was demonstrated by drug detected in tear fluid. No measurable levels of drug were detected in plasma, confirming no systemic exposure.
OTX-TP1 exhibited no ocular or systemic toxicity in a clinically relevant canine model. OTX-TP1 demonstrated sustained local drug delivery. In a clinical setting, administration of a biodegradable sustained release travoprost punctum plug may improve patient compliance with relative to eye drop administration and be a safer and more convenient alternative to eye drops.
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