September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A Phase 1 Pharmacokinetic Study to Assess the Relative Systemic Bimatoprost Exposure Following Placement of a Novel Bimatoprost Ocular Insert in Healthy Adults
Author Affiliations & Notes
  • Gary Walker
    Clinical Research, ForSight VISION 5, Menlo Park, California, United States
  • James E Patrick
    Patrick's Pharmaceutical Consulting, LLC, Aiken, South Carolina, United States
  • Kenneth N Sall
    Sall Eye Research Medical Center, Artesia, California, United States
  • William G Kramer
    Kramer Consulting, LLC, North Potomac, Maryland, United States
  • Robyn L Phelps
    PharmAdvance Consulting, Inc, Sequim, Washington, United States
  • Shweta Soni
    Clinical Research, ForSight VISION 5, Menlo Park, California, United States
  • Melanie Gee-Shihabi
    Intertek Pharmaceutical Services, San Diego, California, United States
  • Charles P Semba
    Clinical Research, ForSight VISION 5, Menlo Park, California, United States
  • Footnotes
    Commercial Relationships   Gary Walker, ForSight VISION 5, Inc (E); James Patrick, ForSight VISION 5, Inc (C); Kenneth Sall, ForSight VISION 5, Inc (F); William Kramer, ForSight VISION 5, Inc (C); Robyn Phelps, ForSight VISION 5, Inc (C); Shweta Soni, ForSight VISION 5, Inc (E); Melanie Gee-Shihabi, ForSight VISION 5, Inc (C), Intertek Pharmaceutical Services (E); Charles Semba, ForSight VISION 5, Inc (E)
  • Footnotes
    Support  ForSight VISION 5, Inc
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3024. doi:
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    • Get Citation

      Gary Walker, James E Patrick, Kenneth N Sall, William G Kramer, Robyn L Phelps, Shweta Soni, Melanie Gee-Shihabi, Charles P Semba; A Phase 1 Pharmacokinetic Study to Assess the Relative Systemic Bimatoprost Exposure Following Placement of a Novel Bimatoprost Ocular Insert in Healthy Adults. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3024.

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

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Abstract

Purpose : In the treatment of glaucoma and ocular hypertension, there is an unmet need to improve adherence to medications to lower intraocular pressure. A novel sustained-release topical ocular insert designed to deliver bimatoprost (BIM) for up to 6-months with a single applied dose is under investigation as an alternative to daily eye drops. Human pharmacokinetics of BIM and BIM-acid after placement of the BIM insert was evaluated.

Methods : A single center, single arm, open-label study was conducted in 11 (6 M, 5 F; mean age 23.5 yrs) healthy adult subjects. After screening with placebo (non-medicated) inserts (OU) for 7-days, eligible subjects had 13 mg BIM inserts placed OU at Day 0. On Day 0, whole blood was obtained at baseline (pre-exposure), then at 2, 5, 10, 15, 30 minutes; 1, 1.5, 2, 4, 6, 8, 12, 24 hours. Additional whole blood samples were obtained on Days 3 and 7. The ocular inserts were then removed. All 11 subjects completed the study. Whole blood concentrations of BIM and BIM-acid were assayed using a validated liquid chromatography atmospheric pressure ionization tandem mass spectrometry (LC-MS/MS) method. The validated linear ranges of the assays for BIM and BIM-acid were 0.025–10.0 ng/mL and 0.050–10.0 ng/mL, respectively. The intra-assay (within-day) and inter-assay (between-day) accuracy and precision for the assay met acceptance criteria.

Results : Transient levels of BIM were observed in whole blood through 72 hours but in the majority of subjects BIM levels were below the limit of quantitation after 8 hours (0.0250 ng/mL), suggesting minimal systemic exposure to BIM from the ocular insert. No detectable levels of BIM were observed at Day 7 in any subject. The geometric mean maximum whole blood concentration of BIM 0.0773 ng/mL occurred at a median Tmax of 10 minutes (0.167 hrs) and the geometric mean AUC (0-t) was 0.1219 hr x ng/mL. The whole blood concentrations of BIM-acid were below the lower limit of quantitation (0.050 ng/mL) of the assay at all time points. There were no serious ocular adverse events (AEs) and ocular AEs were generally mild and consistent with BIM exposure.

Conclusions : A novel sustained release BIM ocular insert was evaluated as a potential alternative to eye drops. There is minimal systemic exposure to BIM from the 13 mg BIM insert (OU) in healthy adult subjects when exposed over a 7-day period.

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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