Background and ObjectivePerampanel is a once-daily oral anti-seizure medication indicated for focal-onset seizures and generalized tonic-clonic seizures. This study investigated the single-and multiple-dose pharmacokinetics of perampanel in healthy Chinese adults. Methods Study 052 (NCT03424564) was a phase I, single-center, open-label, parallel-group study. In the single-dose part of the study, subjects received a single oral dose of perampanel 2, 4, or 8 mg. In the multiple-dose part, subjects received once-daily oral perampanel 2 mg on Days 1-7 and 4 mg on Days 8-21. Pharmacokinetic parameters were determined from perampanel plasma concentrations using non-compartmental analysis. Dose proportionality after single doses of perampanel was assessed. Safety and tolerability were evaluated. Results In the single-dose part (N = 30), median time to reach maximum concentration (t max ) was 0.75-1.0 h, mean terminal elimination phase half-life (t ½ ) was 85.6-122 h, mean maximum observed concentration (C max ) was 77.9-276 ng/mL, and mean area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC (0-t) ) was 4070-15100 ng•h/mL. Single-dose pharmacokinetics were linear for perampanel 2-8 mg. In the multiple-dose part (N = 12), Day 21 steady-state (4 mg/day) parameters were median time at which the highest drug concentration occurs at steady state (t ss,max ), 1.25 h; mean t ½ , 109 h; mean maximum observed concentration at steady state (C ss,max ), 453 ng/mL; and mean area under the concentration-time curve over the dosing interval on multiple dosing (AUC (0-τ) ), 7540 ng•h/mL. For single-and multiple-dose perampanel, the most common treatment-emergent adverse events were dizziness and somnolence. Conclusions Single-and multiple-dose pharmacokinetics of perampanel in healthy Chinese adults revealed rapid perampanel absorption, slow elimination, and a linear relationship with single perampanel doses of 2-8 mg. Findings were consistent with previous studies of perampanel pharmacokinetics in other ethnic/racial populations of healthy subjects. Single and multiple doses of perampanel were generally safe and well tolerated. Clinical Trial Registration NCT03424564; registered February 2018.
CSPCHA115 is a highly selective and potent antagonist of chemoattractant receptor‐homologous molecule expressed on TH2 cells (CRTH2). This study aimed to evaluate the pharmacokinetics (PKs), safety, and tolerability of single and multiple ascending doses of CSPCHA115 in Chinese healthy subjects. Two phase I studies both adopted a randomized, double‐blind, placebo‐controlled, single‐center, and ascending‐dose design. In the single ascending dose (SAD) study, subjects were randomly allocated to receive a single dose of CSPCHA115 (25–1000 mg) or a placebo. In the multiple ascending dose (MAD) study, 100, 200, 400, or 600 mg of CSPCHA115 or placebo were given to subjects once daily for 7 days. PK parameters were estimated by noncompartmental analysis. Safety was assessed by monitoring treatment‐emergent adverse events (TEAEs), clinical laboratory tests, electrocardiograms, vital signs, and physical examinations throughout the study period. Forty‐eight healthy subjects were enrolled in the SAD study, and 40 healthy subjects were in the MAD study. Following single and multiple administrations, CSPCHA115 was rapidly absorbed with a median time to maximum concentration of ~0.5–3.5 h; and the systemic exposure of CSPCHA115 generally increased dose‐proportionally within the dose range studied. Steady‐state was approximately achieved by day 5, and <1.5‐fold accumulation was observed following multiple doses. Mean terminal half‐life was ~8.16–16.43 h after a single dose. CSPCHA115 was well‐tolerated in both studies, with a low overall incidence of TEAEs. The most common TEAE related to CSPCHA115 was hypertriglyceridemia. No significant safety concerns were identified in healthy subjects.
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