Phase 1 trial shows linear pharmacokinetics and good tolerability for HRS-8427 in healthy Chinese adults
This phase 1 randomized controlled trial assessed the pharmacokinetics, safety, and tolerability of the novel anti-carbapenem-resistant cephalosporin HRS-8427 in 79 healthy Chinese adults. The study used single ascending doses (400-6,000 mg) and multiple ascending doses (1,000-3,000 mg every 8 hours). The setting and comparator were not reported.
Pharmacokinetic analysis showed approximately dose-proportional increases in Cmax and AUC across the single-dose range of 400-6,000 mg, though drug exposure increased slightly less than the dose. The mean plasma half-life ranged from 3.89 to 4.28 hours. The drug was primarily excreted unchanged in urine (62.13% to 71.12% of the dose). With multiple dosing every 8 hours, there was minimal systemic accumulation of Cmax and AUC, and pharmacokinetics did not change with repeated administration.
Regarding safety, 62 treatment-emergent adverse events occurred in 29 subjects, yielding an incidence of 36.7% (29/79). No serious adverse events were observed. Three subjects withdrew due to adverse events (one in the 2,000 mg single-dose group and two in the 3,000 mg multi-dose group). The study concluded that both single and multiple intravenous doses, up to 6,000 mg and 2,000 mg respectively, were well tolerated.
Key limitations include the early-phase design, the healthy volunteer population, and the absence of efficacy data or a reported comparator. The funding and conflicts of interest were not reported. Practice relevance is limited as this is a first-in-human safety and pharmacokinetic study; clinical utility for treating infections remains to be established in patient trials.
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