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Madalina Natu Tavares, Mirian Gillissen, George Mihov; Pathway of injectable PEA microfibers to clinical development: preclinical safety evaluation in support of First-in-Man clinical study. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6422.
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© ARVO (1962-2015); The Authors (2016-present)
Compliance with topical drugs for the treatments for ocular hypertension and glaucoma is poor, and therefore sustained release dosage forms are desired to advance the treatment of these diseases. Subconjunctival administration of DSM’s polyesteramide (PEA) microfiber drug delivery implants have the potential to deliver the active compound over a multi-month period of time and degrade safely in the ocular tissue (M. Kropp et al. 2014, J. Thies et al. 2014). To advance DSM’s PEA microfiber into first-in-man studies, key safety and tolerability attributes in GLP toxicology studies were evaluated.
New Zealand white rabbits were used to evaluate safety and tolerability in GLP toxicology studies for 12 months. Single dose, triple dose, placebo and sham groups were included in the study. Clinical ophthalmic examinations (slit-lamp biomicroscopy, indirect ophthalmoscopy) and intraocular pressure measurements (IOP) were performed and examinations utilized a modified McDonald-Shadduck scoring system. Terminal investigations included histopathlogy analysis, while in vivo microfiber degradation was evaluated at 4, 6, 9 and 12 months.
Gross ocular observations found ocular swelling and irritation in most study animals one day after test article implantation, which resolved over the following days. These observations were seen in all groups, including control and sham groups, indicating that they were likely due to the implantation procedure and unrelated to the test article. Clinical ophthalmic examinations similarly found conjunctival congestion and swelling in the days immediately following test article implantation in most study animals, a finding that resolved at later time points. Later findings of occasional conjunctival congestion, swelling, and discharge were scattered, not systematically correlated with any group, and generally resolved quickly. No adverse events were observed over the course of the study suggesting both the microfiber and its degradation products are well tolerated. No adverse changes in IOP were observed during the first 6 months of the study.
Subconjunctival administration of DSM’s polyesteramide (PEA) microfibers resulted in safety and tolerability observations which were mild and transient.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
Conjunctival swelling in single dose group
Conjunctival swelling in triple dose group
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