Safety of the Dexamethasone Punctum Plug is Demonstrated in a Canine
Toxicity Study
Author Block: C. Blizzard, A. Desai, A. Sawhney, M. McGrath, P. Jarrett, A. Driscoll, B. Cowe, D.
Molla, M. O’Connor
Purpose: To evaluate the potential ocular toxicity, irritation and systemic toxicity of the
Dexamethasone Punctum Plug (OTX-DP) after insertion in beagles over a 35-day period and
the reversibility, persistence, and delayed occurrence of any toxic effects after a recovery
period.
Methods: The study conformed to FDA 21 CFR, Part 58 GLP for Non Clinical Laboratory
Studies. OTX-DP was inserted in the vertical canaliculus bilaterally in 16 canines. A control
group of 16 canines had a blank vehicle punctum plug administered in one eye and the
contralateral eye received an insertion sham procedure. Ophthalmic examinations included slit
lamp biomicroscopy, fluorescein staining, fundoscopy and tonometry. Daily clinical
observations, daily food checks, and weekly weight measurements were performed. Canines
were sacrificed at Day 36 or after a 14 day recovery period (Day 50) and necropsy was
performed. Clinical pathology samples were collected (hematology, clinical chemistry,
coagulation, and urinalysis). Histopathology of the lacrimal anatomy and eye for each implant
site, nasal turbinates and adrenal gland was performed. Analysis of drug in plasma and tear
fluid samples was performed. Intraocular pressure (lOP) was measured over the study
duration.
Results: Pharmacokinetics
demonstrated dexamethasone release
into canine tear fluid over the study
duration (ARVO 2013 Abstract #1089).
Plasma drug levels were absent
demonstrating only localized delivery
with no systemic exposure. The
principal findings are summarized in
Table One. There were no findings of
ocular, local or systemic toxicity. No
effects were observed on body weights,
food consumption, hematology, clinical
chemistry, coagulation or urinalysis. Ophthalmic examinations indicated none to only mild
irritation that were comparable across all groups. Posterior eye segment scoring was normal.
The drug product was stable over the study duration. No delayed toxic occurrences after
recovery. lOP was in normal range for all animals.
Conclusions: OTX-DP is a biodegradable punctum plug capable of delivering dexamethasone
for up to one month for the treatment of ocular inflammation. OTX-DP at an elevated dose was
evaluated in beagles. Results demonstrated ocular and systemic safety when exposed to
dexamethasone delivered from OTX- DP over 35 days. Findings established that the OTX-DP
and insertion procedure were well tolerated in all animals.