This double-blind, placebo-controlled, single ascending dose study is designed to demonstrate safety, tolerability and pharmacokinetics of SKI-O-703 in healthy volunteers. The results of this study will guide selection of dose levels for future multiple dose studies in healthy volunteers and adult patients with moderately to severely active rheumatoid arthritis.
This is a double-blind, placebo-controlled study in healthy adult volunteers that will be conducted to evaluate the safety, tolerability, and pharmacokinetics of ascending single doses of SKI-O-703. A total of 48 subjects are planned to participate in 6 cohorts (8 subjects each). In each cohort, 6 subjects will be randomly assigned to receive SKI-O-703 and 2 subjects will be randomly assigned to matching placebo. Dosing will be initiated in the 50 mg dose cohort and sequentially escalated to the 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg cohorts.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
48
SKI-O-703 25 mg capsule or 200 mg capsule without excipient
Placebo 180 mg capsule filled with microcrystalline cellulose
PPD Development, LP
Austin, Texas, United States
Number of participants (Healthy Volunteers) with reported adverse events receiving single dose of SKI-O-703 as assessment of safety and tolerability.
Safety and tolerability of SKI-O-703 as measured by subject incidence of treatment-related Adverse Events.
Time frame: 28 days
Area under the concentration versus time curve from time 0 to the last quantifiable concentration (AUC0-t) for estimating the pharmacokinetic parameters of SKI-O-592 (the free base of SKI-O-703) and its metabolites.
AUC0-t will be reported
Time frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4
Area under the concentration versus time curve from time 0 extrapolated to infinity (AUC0-inf)
AUC0-inf will be reported
Time frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4
Maximum observed plasma concentration (Cmax)
Cmax will be reported
Time frame: Days 0 (pre-dose), 1 (dosing), and post-dose at days 2, 3 and 4
Time to reach the maximum observed plasma concentration (Tmax)
Tmax will be reported
Time frame: Day 0 (pre-dose), Day1 (dosing), and post-dose at days 2, 3 and 4
Apparent terminal elimination half-life (T1/2)
T1/2 will be reported
Time frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4
Apparent volume of distribution (Vd/F) (SKI-O-592, free base of SKI-O-703)
Vd/F will be reported
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Time frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4
Apparent oral clearance (CL/F) (SKI-O-592 only)
CL/F will be reported.
Time frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4
Terminal elimination rate constant (Kel)
Kel will be reported.
Time frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4
Mean residence time (MRT)
MRT will be reported.
Time frame: Day 0 (pre-dose), Day 1 (dosing), and post-dose at days 2, 3 and 4
Metabolite ratio (Rmet), calculated as AUC0-t (metabolite) / AUC0-t (parent) (metabolites M1, M2 and M4 only).
Rmet will be reported.
Time frame: Day 0 (pre-dose), Day 1 (dosing) and post-dose at Days 2, 3 and 4
Renal clearance (SKI-O-592, free base of SKI-O-703 only)
Renal clearance will be reported.
Time frame: Day 1 (dosing), and post-dose at days 2, 3 and 4
Amount of drug excreted in urine over the collection intervals of 0 to 4 hours (Ae0-4), 4 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 48 hours, and 48 to 72 hours post dose.
Ae will be reported
Time frame: Day 1 (dosing), and post-dose at days 2, 3 and 4