Abstract
BACKGROUND: Cipepofol (HSK3486), a gamma-aminobutyric acid type A (GABAA) receptor agonist, has garnered considerable attention as a potential alternative to propofol. This study aimed to evaluate the effects of a single intravenous (IV) bolus dose of cipepofol (0.4 mg/kg) on QTc interval in healthy subjects. PATIENTS AND METHODS: This was a single-center, randomized, blinded (except for moxifloxacin), placebo- and positive-controlled study with a six-sequence, three-period crossover study. Subjects were randomized to 1 of 3 treatment groups in each period: Group A (placebo); Group B (single dose of 0.4 g moxifloxacin, positive control); and Group C (cipepofol [HSK3486], 0.4 mg/kg via IV bolus). The primary endpoint was the change-from-baseline in QTc interval, corrected for heart rate (HR) using the individual QT correction method (QTcI) - ΔQTcI. Secondary endpoints included change-from-baseline in other electrocardiographic (ECG) parameters. Safety/tolerability and pharmacokinetics of cipepofol were also assessed. RESULTS: Forty-eight subjects were randomized, and demographic characteristics were comparable across the six sequences. The LS mean placebo-corrected ΔQTcI (ΔΔQTcI) interval following cipepofol bolus ranged from -1.7 to 4.1 milliseconds. The upper bound of the two-sided 90% confidence interval for ΔΔQTcI interval remained < 10 milliseconds at all post-dose timepoints. In addition, no clinically significant effects of cipepofol were observed on the PR interval or QRS interval (ventricular depolarization time). Assay sensitivity was successfully demonstrated by the expected QTc interval prolongation within 2-4 h post-moxifloxacin administration. No subjects in the cipepofol treatment period developed a new QTcI interval >480 or an increase in QTcI interval from baseline >60 milliseconds. All adverse events were mild to moderate in severity, and no serious adverse events or deaths occurred. CONCLUSION: Cipepofol exhibited no clinically relevant effects on the QTc interval or other ECG parameters, and was safe and well tolerated in healthy subjects. CLINICAL TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT06379867).