A First-in-human Safety, Tolerability and Pharmacokinetics study of Benapenem in Healthy Chinese Volunteers [Clinical Therapeutics]

Objective: The objective of this trial is to investigate the safety, tolerability and pharmacokinetics (PK) of benapenem administrated by single or multiple intravenous infusions in healthy Chinese volunteers.

Methods: The trial was divided into 3 parts. Part A: 94 subjects were enrolled in a double-blind, placebo-controlled, sequential ascending single-dose study. The subjects were randomly assigned to groups receiving placebo or benapenem for injection at doses of 62.5, 125, 250, 500, 1000, 2000 or 3000 mg, respectively. The effects of intravenous infusion time on the subjects of 250, 500 and 1000 mg group were explored. Part B: 12 subjects were enrolled in a single-dose PK study under fasting conditions receiving 250, 500 or 1000 mg of benapenem for injection. Part C: 36 subjects were given 250, 500 and 1000 mg of benapenem for injection once daily for 7 consecutive days.

Findings: The results showed that benapenem for injection was well tolerated during the studies. The major observed adverse events were mild and all were resolved spontaneously without any medical intervention. Benapenem was mainly excreted through the kidneys in the form of parent molecule and metabolites.

Implications: The PK and safety profiles of benapenem in healthy Chinese volunteers support its once-daily dosing in future clinical investigations. (Part A, Part B & Part C has been registered at ClinicalTrials.gov under identifier NCT03588156, NCT03578588 & NCT03570970, respectively.)

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