This double-blind, placebo-controlled, multiple ascending dose study is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of SKI-O-703 in healthy volunteers.
This is a double-blind, placebo-controlled study in healthy adult volunteers, to evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple ascending doses of SKI-O-703. A total of 24 subjects are planned to participate in 3 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 with a 200 mg once daily (QD) dose cohort and escalated to 400 mg QD, under fasting conditions, for 7 days. In the third cohort, a 200 mg twice daily (BID) dose will be studied for 7 days. Evening dosing will occur 12 hours after the morning dose and will be preceded by fasting for at least 3 hours. After all 8 subjects in each cohort have received the study drug and been monitored, the decision to escalate to the next dose cohort will be made.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
24
SKI-O-703 200 mg capsule with no inactive excipients.
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 multiple 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: 21 days
Area under the concentration versus time curve within a dosing interval (AUC0-tau), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
AUC0-tau will be reported.
Time frame: Days 1-7 (dosing), post-dose (days 8-10).
Area under the concentration versus time curve from time 0 to the last measurable concentration (AUC0-t), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
AUC0-t will be reported.
Time frame: Days 1-7 (dosing), post-dose (days 8-10).
Area under the concentration versus time curve within a dosing interval (AUC0-inf), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
AUC0-inf will be reported.
Time frame: Day 7 only
Maximum observed concentration (Cmax), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
Cmax will be reported.
Time frame: Days 1-7 (dosing), post-dose (days 8-10).
Apparent oral clearance (CL/F), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
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CL/F will be reported.
Time frame: Days 1-7 (dosing), post-dose (days 8-10).
Terminal elimination rate constant (Kel), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
Kel will be reported.
Time frame: Day 7
Time to reach the maximum observed concentration, to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
Tmax will be reported.
Time frame: Days 1-7 (dosing), post-dose (days 8-10).
Apparent terminal elimination half-life (t1/2), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
t1/2 will be reported.
Time frame: Day 7 only
Apparent volume of distribution (Vd/F), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
Vd/F will be reported.
Time frame: Days 1-7 (dosing), post-dose (days 8-10).
Metabolite ratio (Rmet), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
Rmet will be reported.
Time frame: Days 1-7 (dosing), post-dose (days 8-10).
Accumulation ratio based on AUC0-tau (RAUC), to investigate pharmacokinetic profiles of SKI-O-592 (the free base of SKI-O-703) and its metabolites (M2 and M4) in healthy volunteers.
RAUC will be reported.
Time frame: Days 1-7 (dosing), post-dose (days 8-10).