July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Pharmacokinetics of OTX-TIC, a Sustained Release Travoprost Intracameral Implant in Rabbits
Author Affiliations & Notes
  • Charles D Blizzard
    Ocular Therapeutix, Inc, Nashua, New Hampshire, United States
  • Ankita Desai
    Ocular Therapeutix, Inc, Nashua, New Hampshire, United States
  • Jennifer Langh
    Ocular Therapeutix, Inc, Nashua, New Hampshire, United States
  • Noah Buff
    Ocular Therapeutix, Inc, Nashua, New Hampshire, United States
  • Jamie L Metzinger
    Ocular Therapeutix, Inc, Nashua, New Hampshire, United States
  • Michael H Goldstein
    Ocular Therapeutix, Inc, Nashua, New Hampshire, United States
  • Ann Gelormini
    Ocular Therapeutix, Inc, Nashua, New Hampshire, United States
  • Arthur Driscoll
    Ocular Therapeutix, Inc, Nashua, New Hampshire, United States
  • Footnotes
    Commercial Relationships   Charles Blizzard, Ocular Therapeutix (E); Ankita Desai, Ocular Therapeutix (E); Jennifer Langh, Ocular Therapeutix (E); Noah Buff, Ocular Therapeutix (E); Jamie L Metzinger, Ocular Therapeutix (E); Michael Goldstein, Ocular Therapeutix (E); Ann Gelormini, Ocular Therapeutix (E); Arthur Driscoll, Ocular Therapeutix (E)
  • Footnotes
    Support  Ocular Therapeutix
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3777. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Charles D Blizzard, Ankita Desai, Jennifer Langh, Noah Buff, Jamie L Metzinger, Michael H Goldstein, Ann Gelormini, Arthur Driscoll; Pharmacokinetics of OTX-TIC, a Sustained Release Travoprost Intracameral Implant in Rabbits. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3777.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : To assess the pharmacokinetic (PK) profile of travoprost release from an intracameral hydrogel implant, OTX-TIC, over 5 months.

Methods : OTX-TIC was injected into the anterior chamber (AC) of 24 New Zealand White rabbits (NZW) through a 27 G needle. Aqueous humor (AH) samples were collected post-dose (n=6 eyes per day for 34 and 63 days; n=12 eyes per day for 91, 126 and 153 days). Drug concentrations in the AH was measured by LC/MS/MS. In vitro drug release was assessed in physiologically representative conditions (PBS, pH 7.4, 37 °C) and analyzed by UPLC/UV.

Results : OTX-TIC, currently in Phase 1 clinical trials, resides in the inferior iridocorneal angle within the AC. It is formulated to release travoprost with zero-order kinetics over 4 months in animals (potentially longer in humans), and approximately 25% of the sustained dose is released in vitro each month. AH samples in NZW rabbits demonstrated elevated travoprost free acid (TFA) levels post-injection through 4 months and an absence at 5 months. The decrease in TFA concentration observed at 126 days corresponds to the decrease in in vitro release rate observed at 119 days. Drug concentrations of 10.9, 20.0 and 8.7 ng/mL at 1, 2 and 3 months, respectively are comparable to the maximum TFA concentration (Cmax) of 10.2 ± 3.0 ng/mL from a single eye drop administration of Travatan Z in NZW rabbits at 1 hour, as reported in the literature (Travatan Z NDA 21-994).

Conclusions : OTX-TIC delivers sustained TFA levels to the AH comparable to the Cmax delivered from a Travatan Z eye drop in NZW rabbits. As OTX-TIC resides in the inferior iridocorneal angle, it potentially releases therapeutic concentrations of TFA into the AH demonstrating promise as a potential sustained release glaucoma treatment.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Schematic of OTX-TIC residing in the iridocorneal angle

Schematic of OTX-TIC residing in the iridocorneal angle

 

Pharmacokinetics of TFA in the AH of NZW rabbits release from OTX-TIC over 5 months and corresponding in vitro travoprost release at relevant periods

Pharmacokinetics of TFA in the AH of NZW rabbits release from OTX-TIC over 5 months and corresponding in vitro travoprost release at relevant periods

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×