September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Safety, Tolerability and Pharmacokinetics of P-321 Ophthalmic Solution in Subjects with Mild to Moderate Dry Eye Disease
Author Affiliations & Notes
  • Jose L Boyer
    Parion Sciences, Durham , North Carolina, United States
  • Anita Woodring
    Parion Sciences, Durham , North Carolina, United States
  • John Ansede
    Parion Sciences, Durham , North Carolina, United States
  • William Thelin
    Parion Sciences, Durham , North Carolina, United States
  • M Ross Johnson
    Parion Sciences, Durham , North Carolina, United States
  • Kenneth N Sall
    Sall Research Medical Center, Artesia, California, United States
  • Gary N Foulks
    University of Louisville, Louisville, Kentucky, United States
  • Richard C Boucher
    University of North Carolina, Chapel Hill, North Carolina, United States
  • Footnotes
    Commercial Relationships   Jose Boyer, Parion Sciences, Inc. (E); Anita Woodring, Parion Sciences, Inc. (E); John Ansede, Parion Sciences, Inc. (E); William Thelin, Parion Sciences, Inc. (E); M Johnson, Parion Sciences, Inc. (E); Kenneth Sall, Parion Sciences, Inc. (C); Gary Foulks, Parion Sciences, Inc. (C); Richard Boucher, Parion Sciences, Inc. (I)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2875. doi:
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    • Get Citation

      Jose L Boyer, Anita Woodring, John Ansede, William Thelin, M Ross Johnson, Kenneth N Sall, Gary N Foulks, Richard C Boucher; Safety, Tolerability and Pharmacokinetics of P-321 Ophthalmic Solution in Subjects with Mild to Moderate Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2875.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To evaluate the safety, tolerability and pharmacokinetics of P-321 Ophthalmic Solution versus placebo in subjects with mild to moderate Dry Eye Disease.

Methods : P-321 is a novel potent epithelial sodium channel (ENaC) blocker formulated as a sterile, non-preserved aqueous solution.
P-321-101 was a single-center, dose escalation, randomized, double-masked, placebo-controlled, Phase 1/2a trial. The study consisted of 4 consecutive cohorts: Cohorts 1-3 evaluated the study drug for up to 15 days and Cohort 4 for 28 days. The concentrations of P-321 were 0.0005%, 0.0015%, 0.005%, and 0.01% for Cohorts 1-4, respectively, delivered as one drop per eye, twice daily. Subjects with mild to moderate dry eye disease were randomized to P-321 or placebo in a 3:1 ratio. Cohorts 1, 2 and 3 consisted of 5 clinical visits with up to 8 subjects enrolled in each cohort, and Cohort 4 consisted of 8 visits and 24 subjects. Safety and tolerability were assessed at each clinic visit. Additional exploratory assessments and drug levels in tears, plasma and urine were conducted.

Results : P-321 Ophthalmic Solution was well tolerated at all concentrations tested. The incidence of adverse events observed in subjects taking P-321 was similar to subjects on placebo. No serious adverse events were reported at any drug level. Seven subjects in the trial experienced 9 drug related events, and all were classified as mild. Two cases of mild conjunctival hyperemia, one in P-321 and one in placebo were observed. No subject discontinued treatment due to an adverse event. No treatment-related safety concerns were observed for ocular surface staining, visual acuity and intraocular pressure. There was no evidence of systemic or clinical laboratory abnormalities. No quantifiable concentrations of drug were found in plasma or urine samples, suggesting that P-321 is not systemically available.

Conclusions : P-321 Ophthalmic Solution was well-tolerated in subjects with mild to moderate dry eye disease at all concentrations with the 0.01% concentration for up to 28 days. There were no serious adverse events or clinically relevant adverse effects on any ocular or systemic safety measures. No evidence of systemic exposure of P-321 was observed.
Further investigations of P-321 Ophthalmic Solution for the treatment of dry eye disease are warranted based on the findings of this study.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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