A phase 1, open-label, single-arm study evaluating the ocular safety of OTX-101 and systemic absorption of cyclosporine in healthy human volunteers

• Published in: Clinical ophthalmology (Auckland, N.Z.) N.Z.), 2019-01, Vol.13, p.591-596
• 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: Article
• Language: English
• Subjects: Blood & organ donations; Consent; cyclosporine; dry eye disease; Electrocardiography; Eye diseases; Family medical history; FDA approval; Laboratories; Ophthalmology; Original Research; Participation; Pharmaceuticals; pharmacokinetic; systemic exposure; Vital signs
• ISSN: 1177-5467; 1177-5483; 1177-5483
• DOI: 10.2147/OPTH.S187945

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. Healthy volunteers ≥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 , ng/mL], time to C [T , hours]), and area under the concentration-time curve from 0 to the last measurement [AUC , 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. 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 ≥LLOQ on day 8; the mean±SD for C was 0.17±0.02 ng/mL, T was 1.5±0.58 hours, and AUC was 0.53±0.06 h·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. 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.