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Eugene B McLaurin, David G Evans, Robert Noecker, Jamie Lynne Metzinger, Deepa Mulani, Jonathan H Talamo; A Single Center Study of the Plasma Pharmacokinetics of DEXTENZATM (dexamethasone insert) 0.4 mg in Healthy Volunteers. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4106.
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To evaluate the plasma pharmacokinetics (PK) of DEXTENZA as an extended release drug (dexamethasone) insert when placed in the canaliculus of the eyelid in healthy volunteers.
This was an open-label, single-center study. DEXTENZA was inserted unilaterally into the inferior canaliculus in eligible patients. During the day of insertion, subjects underwent blood draws at 1 hour (± 30 min) pre-insertion and at the following post-insertion schedule: Hours 1, 2, 4, 8 and 16. Follow-up visits occurred at Days 2, 4, 8, 15, 22 and 29 for additional plasma collection. The primary PK endpoints evaluated were Cmax, AUC and Tmax. Other parameters evaluated included ease of insertion, presence of insert at all study visits, ease of product visualization, and if necessary, ease of removal. During the study period, subjects were monitored for adverse events that may be associated with the placement and subsequent presence of DEXTENZA.
A total of 16 healthy volunteers ranging from 19 to 55 years (mean: 31.7 years) were enrolled; a majority of subjects were female (68.7%). Plasma concentrations of dexamethasone were below the lower limit of quantitation (LLOQ = 0.05 ng/mL) at all time-points in 5 of the 16 subjects. In the remaining 11 subjects, plasma dexamethasone concentrations were below LLOQ at 1 and 2 hours post-insertion, and at the Day 15, 22 and 29 Visits. In the 11% of samples (21 of 190) that were above the LLOQ, plasma dexamethasone concentrations ranged from 0.05 ng/mL to 0.81 ng/mL. Plasma concentrations did not appear to be related to age, gender, or body weight of subjects. Four subjects (25%) experienced a total of four adverse events (AEs). Three subjects (18.7%) experienced elevated IOP; the event was considered related to treatment, of mild severity, and resolved upon removal or hydrolysis of DEXTENZA. No serious AEs were reported.
The results of this study indicate that DEXTENZA results in negligible systemic exposure to dexamethasone with the vast majority of samples being below the LLOQ; this result is in line with previous studies. Elevated IOP in phakic patients with young, healthy eyes is congruent with the mechanism of action. The safety profile of DEXTENZA is consistent with that reported previously with the ocular administration of dexamethasone.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Mean Plasma Concentration of Dexamethasone vs. Time
Overall Summary of Adverse Events
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