Safety, Tolerability, and Pharmacokinetics of Kukoamine B in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Phase I Study.

Introduction: Kukoamine B (KB) is a novel sepsis therapeutic drug targeting lipopolysaccharide and CpG DNA. This study aims to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of multiple doses of KB in healthy volunteers.

Methods: Healthy volunteers were randomized at a 1:1:1:1 ratio to receive multiple intravenous infusion doses of KB 0.06 mg/kg, 0.12 mg/kg, 0.24 mg/kg or placebo (administered every 8 h per day) for 7 days and subsequently followed up for another 7 days at Peking Union Medical College Hospital. Primary endpoints were adverse events (AEs), and the secondary endpoints were PK parameters of the first administration and the last administration.

Results: Data of the 18 health volunteers in KB groups and 6 in the placebo group were pooled and analyzed. AEs occurred in 12 (66.67%) volunteers in the KB groups and 4 (66.67%) volunteers in the placebo group. Treatment-related adverse events (TRAEs) occurred in 8 (44.44%) volunteers in the KB groups and 2 (33.33%) volunteers in the placebo group. Hypertriglyceridemia (4 [22.22%] vs. 2 [33.33%]) and sinus bradycardia (3 [16.67%] vs. 0) were the most common AEs. The mean elimination half-life, clearance, and distribution volume of KB were 3.40-4.88 h, 9.35-13.49 L/h, and 45.74-101.90 L, respectively. The average accumulation ratios of area under the plasma concentration-time curve and maximum plasma concentration were 1.06 and 1.02, respectively.

Conclusion: Single and multiple intravenous infusions of KB at a dose range of 0.06-0.24 mg/kg are safe and tolerable in healthy volunteers.

Trial Registration: ClinicalTrials.gov identifier, NCT02690961.