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Glenn Noronha, Henry F Edelhauser, Samir Patel, Brian Burke, Rozemarijn S Verhoeven; Safety and toxicokinetics of suprachoroidal space (SCS) injections of CLS1001 (triamcinolone acetonide, TA) in albino rabbits. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4887.
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© 2017 Association for Research in Vision and Ophthalmology.
To evaluate the ocular tolerance and toxicokinetics of two bilateral SCS injections of TA in albino rabbits.
Sixteen male and female New Zealand White rabbits were randomized according to body weight and assigned to treatment groups (4 rabbits/sex/group). Each animal received a bilateral SCS injection of vehicle (100 μL) or TA (100 μL of 40 mg/mL) on Day 0 and Day 90. The injection was administered using a microneedle (750±25 μm, Clearside Biomedical, Alpharetta, GA). External and/or subconjunctival reflux was observed immediately following SCS injection in all groups. Therefore the delivered dose is presented as a theoretical dose. Animals were clinically observed daily over 1 month and then two times/week. Ophthalmic examinations with modified McDonald-Shadduck scoring, intraocular pressure (IOP), fundus assessment, and systemic exposure to TA were conducted at baseline, Days 1, 7, 14, 28, 60, 90, 91, 97, 104, 118, 150, and week 26. Day 90 assessments were made before the 2nd dosing. Macroscopic observations at necropsy, ocular histopathology, electroretinography, and central corneal thickness (CCT) were measured at baseline, Day 1, and Week 26. Blood sampling for hematology and biochemistry analysis were collected prior to necropsy.
All animals were in good health throughout the study. There were no treatment- or administration-related effects on food or water consumption, clinical observations, ophthalmic examinations, CCT, hematologic or biochemical parameters, or electroretinography. Decreased IOP was observed in all groups on Days 1 and 91. Increased IOP (~2-3 mmHg, not considered adverse) was observed in the TA group compared to vehicle. No effects were observed at necropsy and there were no adverse effects related to the test item or method of administration as assessed by histopathology on Day 1 or Week 26. Conjunctival inflammatory cells and edema of the ciliary processes were observed in both groups on Days 1 and 91 but not considered adverse. Plasma TA concentration peaked on Day 1 with a mean Cmax of 12 ng/mL; it was still quantifiable at very low levels in individual animals on Day 60, and was undetectable in all but one animal by Week 13.
Two bilateral SCS injections of TA or vehicle delivered at a 90 day interval over a period of 26 weeks were well tolerated in albino rabbits. Systemic exposure was minimal.
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