Phase I Randomized Study of SCAI-005 Ophthalmic Solution: Safety, Tolerability, and Pharmacokinetics in Healthy...

To evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of SCAI-005-a topical ophthalmic solution of axitinib for neovascular age-related macular degeneration (AMD), a VEGF receptor tyrosine kinase inhibitor-following single and multiple ascending doses (SAD and MAD) in healthy Korean adults.

Randomized, double-masked, placebo-controlled, single- and multiple-ascending-dose phase I study.

Forty-eight healthy Korean adults were randomized 3:1 (active:placebo) into six cohorts across SAD (0.04% as a single drop, 0.08% as a single drop, and 0.08% as two drops) and MAD (0.04% 1 drop three times daily (TID), 0.08% 1-drop TID, and 0.08% two-drop TID for 7 days) groups.

SCAI-005 or placebo was administered topically to 1 eye per subject. Serial blood samples were collected for systemic PK analysis using noncompartmental analysis. Safety was assessed through treatment-emergent adverse events (TEAEs), ophthalmic examinations, vital signs, electrocardiography, and clinical laboratory tests.

Primary outcomes were safety and tolerability. Secondary outcomes included systemic PK parameters (C_max and AUC_last) and dose proportionality.

Forty-seven of 48 subjects (97.9%) completed the study. TEAEs were reported in 7 subjects (14.6%), with no obvious dose-dependent trend in this small sample. All treatment-related TEAEs were grade 1 in severity. No clinically significant changes were observed in ophthalmic assessments. SCAI-005 was rapidly absorbed following topical administration, with day 8 postdose peak systemic concentrations (C_max) approximately 66- to 282-fold lower than the reported steady-state C_max for oral axitinib 5 mg twice daily. Because predose trough concentrations were below the assay limit in most subjects, formal steady state could not be confirmed; repeated-dose parameters are therefore reported as day 8 postdose descriptive PK parameters. In the dose proportionality analysis, C_max findings were broadly consistent with dose proportionality in both SAD and MAD cohorts. AUC_last slope estimates were above unity in both cohorts (1.64-1.69) with confidence intervals not including unity.

Topical SCAI-005 was generally well tolerated in this small first-in-human study in healthy Korean adults, producing low systemic axitinib exposure and no obvious short-term safety signal. These findings will require confirmation in phase II studies enrolling the target neovascular AMD population.

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