Pharmacokinetics, Safety, and Tolerability of Intravenous Felbinac Trometamol in Healthy Chinese Volunteers: A First-in-Human Single- and Multiple-Dose Escalation Phase I Study with a Randomized, Double-Blind, Placebo-Controlled Design.

Min Wu, Cuiyun Li, Hong Zhang, Jixuan Sun, Xiaoxue Zhu, Xiaojiao Li, Xuedong Gao, Wei Wang, Yanhua Ding

CNS drugs 2020 Aug

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Felbinac trometamol, an anti-inflammatory and analgesic drug, has been used to treat immediate postoperative pain. The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics of single or multiple intravenous infusions of felbinac trometamol in healthy Chinese volunteers. A total of 56 healthy subjects were enrolled in a single-ascending dose study (11.78-377.00 mg), meanwhile 36 subjects were enrolled in a multiple-ascending dose study (47.13-188.50 mg). Safety endpoints included treatment-emergent adverse events, vital signs, electrocardiograms, and laboratory parameters. Pharmacokinetic endpoints included exposure of subjects to felblinac and metabolites of the drug in plasma, urine, and feces. Felblinac time to maximum plasma concentration was obtained at 0.5 h, corresponding to the end of the infusion. Maximum plasma concentration and area under the curve increased in a dose-dependent manner for felblinac and its metabolite, showing linear pharmacokinetic characteristics at single and multiple doses. After intravenous infusions of multiple doses three times (30 min each time) per day, the accumulation ratio of felblinac and its metabolite based on the area under the curve had a range of 1.34-1.45 and 1.60-1.87, respectively, across cohorts. After administration of the fourth dose, the plasma concentration of both felblinac and its metabolites was maintained at a steady state. Felbinac trometamol was well tolerated. Neither treatment-emergent adverse event frequency nor severity increased with increasing felbinac trometamol dose. Felbinac trometamol was well tolerated in our study. Based on the dose range in this study, 94.25 mg is the recommended target dose for a phase II study. CTR20170496 and CTR20180896. The dates of registration are 2017-06-19 and 2018-07-02 ( https://www.chinadrugtrials.org.cn/ ).

Citation

Min Wu, Cuiyun Li, Hong Zhang, Jixuan Sun, Xiaoxue Zhu, Xiaojiao Li, Xuedong Gao, Wei Wang, Yanhua Ding. Pharmacokinetics, Safety, and Tolerability of Intravenous Felbinac Trometamol in Healthy Chinese Volunteers: A First-in-Human Single- and Multiple-Dose Escalation Phase I Study with a Randomized, Double-Blind, Placebo-Controlled Design. CNS drugs. 2020 Aug;34(8):867-877