A phase I, open-label, single-arm study evaluating the ocular safety of OTX-101 and systemic absorption of cyclosporine in healthy human volunteers

Purpose: To evaluate the ocular safety of OTX-101 0.09%--a novel, nanomicellar, clear, aqueous solution of cyclosporine (CsA)--and to determine the systemic exposure to CsA following ophthalmic administration. Patients and methods: Healthy volunteers [greater than or equal to]18 years of age were re...

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Published inClinical ophthalmology (Auckland, N.Z.) p. 591
Main Authors Karpecki, Paul M, Weiss, Sidney L, Kramer, William G, O'Connor, Patrick, Evans, David, Johnston, Josh, Jasper, April L, Justice, Angela, Ogundele, Abayomi B, Devries, Doug
Format Journal Article
LanguageEnglish
Published Dove Medical Press Limited 01.04.2019
Subjects
Analysis
Chromatography
Cyclosporins
Diseases
Eye diseases
Itching
Labels
Liquid chromatography
Mass spectrometry
Pharmaceutical industry
Spectroscopy
Time
India
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Summary:Purpose: To evaluate the ocular safety of OTX-101 0.09%--a novel, nanomicellar, clear, aqueous solution of cyclosporine (CsA)--and to determine the systemic exposure to CsA following ophthalmic administration. Patients and methods: Healthy volunteers [greater than or equal to]18 years of age were recruited for participation in this phase 1, open-label, single-center, single-arm, study. Subjects received one drop of OTX-101 0.09% in each eye every 12 hours for 7 days, and once on day 8. Blood samples were collected predose, and 0.25, 0.5, 1, 2, 4, 8, and 12 hours post-first dose on day 1 and day 8. CsA levels in whole blood samples were analyzed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters (maximal whole blood concentration [[C.sub.max], ng/mLl, time to [C.sub.max] [[T.sub.max], hoursl), and area under the concentration-time curve from 0 to the last measurement [[AUC.sub.(0-t)], h-ng/mL]) were calculated using noncompartmental analysis. Safety assessments included subject-reported adverse events (AEs), vital signs, visual acuity, intraocular pressure measurement, biomicroscopy, and direct ophthalmoscopy. Results: A total of 16 subjects were enrolled; 15 subjects completed the study. Blood sample analysis indicated limited systemic exposure to CsA; three subjects had a CsA concentration greater than or equal to the lower limit of quantitation (LLOQ) on day 1; only four subjects had three consecutive CsA concentration measurements [greater than or equal to]LLOQ on day 8; the mean[+ or -]SD for [C.sub.max] was 0.17[+ or -]0.02 ng/mL, [T.sub.msx] was 1.5[+ or -]0.58 hours, and [AUC.sub.(0-t)] was 0.53[+ or -]0.06 h x ng/mL. Three subjects reported three AEs (eye pain, eye pruritis, and eye irritation) during the study. No clinically significant changes in the safety assessments were noted. Conclusion: The OTX-101 formulation was well tolerated. Systemic exposure to CsA was negligible in healthy volunteers after twice-daily ocular administration. No evidence for systemic accumulation of CsA was observed. Keywords: dry eye disease, cyclosporine, pharmacokinetic, systemic exposure
ISSN:1177-5483
1177-5483
DOI:10.2147/OPTH.S187945