First-in-human, phase I single-ascending-dose study of the safety, pharmacokinetics, and relative bioavailability of selatinib, a dual EGFR-ErbB2 inhibitor in healthy subjects.
Summary: We assessed the pharmacokinetics and safety of a single oral administration of selatinib to healthy Chinese subjects and evaluated the potential bioavailability advantage of selatinib relative to lapatinib. Healthy subjects aged 18–40 years were enrolled in this two-part study: Part 1, a si...
| Publicado en: | Investigational New Drugs Vol. 38; no. 6; pp. 1826 - 1836 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Dec2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=146533709&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 146533709 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01676997 OH2 jtl: Investigational New Drugs issn: 01676997 maglogo: N pubinfo: dt: Dec2020 vid: 38 iid: 6 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 146533709 143983484 146533709 146533709 10.1007/s10637-020-00959-6 146533709 ppf: 1826 ppct: 10 formats: tig: atl: First-in-human, phase I single-ascending-dose study of the safety, pharmacokinetics, and relative bioavailability of selatinib, a dual EGFR-ErbB2 inhibitor in healthy subjects. aug: au: Wang, Meng-na Kuang, Yun Gong, Li-ying Hua, Ye Pei, Qi Guo, Cheng-xian Cao, Yu Huang, Jie Yang, Guo-ping affil: Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, 410013, Changsha, Hunan, People's Republic of China sug: subj: Biological Availability Tyrosine Kinase Inhibitors Pharmacokinetics Tyrosine Kinase Inhibitors Therapeutic Use Human Adolescence Adult Tyrosine Kinase Inhibitors Diarrhea Tyrosine Kinase Inhibitors Adverse Effects Descriptive Statistics Safety Random Assignment Crossover Design Epidermal Growth Factors Adolescent: 13-18 years Adult: 19-44 years ab: Summary: We assessed the pharmacokinetics and safety of a single oral administration of selatinib to healthy Chinese subjects and evaluated the potential bioavailability advantage of selatinib relative to lapatinib. Healthy subjects aged 18–40 years were enrolled in this two-part study: Part 1, a single ascending dose (50–500 mg), randomized, double-blind, placebo-control study with 64 subjects; and Part 2, an open-label, positive control, randomized, three-treatment, three-period, three-sequence crossover design study, with 6 subjects administered a single 500-mg dose of selatinib tablets (A), selatinib suspension (B), or lapatinib tablets C) per cycle. In part 1, selatinib was well-tolerated up to the planned maximum dose of 500 mg; thus the maximum tolerated dose was not attained. Twenty-two adverse events were observed in 19 (36.5%) of the 52 subjects administered the test drug. The most common drug-related adverse event was diarrhea. The mean selatinib peak plasma concentration was 69.4–494 ng/mL, which was achieved in a median peak time of 3.5–4.5 h, with a mean elimination half-life between 13.8 and 15.8 h. In Part 2, A and B showed similar bioavailability. Plasma exposure to the active drug (selatinib plus the metabolite, lapatinib) after A intake was more than two-fold higher than that of the same dose of C. In the dose range of 50–500 mg, selatinib was safe and well-tolerated by healthy Chinese subjects, and it conformed with linear pharmacokinetics. Active exposure to selatinib was much greater than that to lapatinib, supporting its development as an adjuvant for anticancer treatment. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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