NCT05042986

A Study of the Absorption, Metabolism, and Excretion of [14C]-SKI-O-703 Following a Single Oral Dose in Healthy Male Subjects

A Phase I, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-SKI-O-703 Following a Single Oral Dose in Healthy Male Subjects

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Oscotec Inc. · Industry
• Sex: Male
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This will be a Phase I, open-label, nonrandomized, single dose study in healthy male subjects. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the dose administration. Subjects will be admitted into the study site on Day -1 and be confined to the study site until at least Day 8. On the morning of Day 1, all subjects will receive a single oral dose of \[14C\]-SKI-O-703. Subjects will be discharged if the following discharge criteria are met: plasma radioactivity levels below the limit of quantitation for 2 consecutive collections, ≥ 90% mass balance recovery, and ≤ 1% of the total radioactive dose is recovered in combined excreta (urine and feces) in 2 consecutive 24-hour periods. If discharge criteria are not met by Day 8, subjects will remain in the study site up to Day 15.

Detailed description

SKI-O-703 is being developed by Oscotec Inc. and is currently being studied for the treatment of adult patients with moderately to severely active rheumatoid arthritis and for the treatment of patients with persistent and chronic immune thrombocytopenia. SKI-O-592 (the free base of SKI-O-703) has demonstrated high selectivity and potency against spleen tyrosine kinase in a biochemical assay. For immunoreceptor activation linked to SYK, the effect of SKI-O-592 on the anti-inflammatory response consisting of tumor necrosis factor alpha, β-hexosaminidase, and CD69 expression was greater than the effects of first-generation SYK inhibitors (eg, R406) in several immune cell lines and in human primary cells. This anti-inflammatory activity was responsible for the selective inhibition of p-SYK (Y525/526), which led to the sequential inhibition of downstream effectors. In vitro studies revealed excellent SYK selectivity of SKI-O-592 that led to no inhibition of SYK-independent signal pathways, indicating that SKI-O-592 shows more potent anti-inflammatory activity to allow continuous administration of SKI-O-703 compared with the first-generation SYK inhibitors. SKI-O-703 is currently not approved or marketed in any country.

Conditions

• Healthy Volunteers

Interventions

Type	Name	Description
DRUG	.[14C]-SKI-O-703	Single oral dose of 200 mg (100 μCi in 200 mg salt \[0.5 μCi/mg as salt\], equivalent to 100 μCi in 142 mg active \[0.7 μCi/mg as active\]) of \[14C\]-SKI-O-703 containing approximately 100 μCi of \[14C\]-SKI-O-703 per capsule after an overnight fast.

Timeline

• Start date: 2021-08-10
• Primary completion: 2021-09-29
• Completion: 2021-09-29
• First posted: 2021-09-13
• Last updated: 2022-04-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study