Effect of a moderate CYP3A inducer efavirenz on the pharmacokinetics of fuzuloparib: An open-label, fixed sequence study in Chinese healthy male subjects.
Summary: To evaluate the potential drug-drug interaction (DDI), safety and tolerability of fuzuloparib co-administered with a moderate CYP3A inducer efavirenz in healthy male subjects. Eighteen healthy male subjects were enrolled in a single-center, single-arm, open-label, fixed-sequence study. Fuzu...
| Published in: | Investigational New Drugs Vol. 41; no. 2; pp. 276 - 284 |
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| Main Authors: | , , , , , , |
| Format: | clinical trial research tables/charts Journal Article |
| Published: |
Springer Nature
Apr2023
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=163391839&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 163391839 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01676997 OH2 jtl: Investigational New Drugs issn: 01676997 maglogo: N pubinfo: dt: Apr2023 vid: 41 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 163391839 161928167 163391839 163391839 10.1007/s10637-023-01331-0 163391839 ppf: 276 ppct: 8 formats: tig: atl: Effect of a moderate CYP3A inducer efavirenz on the pharmacokinetics of fuzuloparib: An open-label, fixed sequence study in Chinese healthy male subjects. aug: au: Hu, Linlin Dou, Ting Sun, Qiuyue Tang, Lu Cai, Mingmin Qian, Wei Wang, Huiping affil: Office of clinical trial institution, Department of Phase I Clinical Trial Unit, Nanjing Zhongda Hospital, Southeast University, School of Medicine, 210009, Nanjing, China sug: subj: Oxidoreductases Efavirenz Pharmacodynamics Enzyme Inhibitors Pharmacokinetics Enzyme Inhibitors Drug Effects Drug Interactions Evaluation Patient Safety Evaluation Drug Tolerance Evaluation Drug Therapy, Combination Health Status Human Male Clinical Trials Enzyme Inhibitors Administration and Dosage Administration, Oral After Care Descriptive Statistics Confidence Intervals Funding Source Male ab: Summary: To evaluate the potential drug-drug interaction (DDI), safety and tolerability of fuzuloparib co-administered with a moderate CYP3A inducer efavirenz in healthy male subjects. Eighteen healthy male subjects were enrolled in a single-center, single-arm, open-label, fixed-sequence study. Fuzuloparib was administered as a single oral 50 mg under a fasting state on day 1, efavirenz (600 mg once daily) was given on days 4–17 before bed time, concomitantly with fuzuloparib on day 18, and for the follow-up 3 additional days (days 19–20). Pharmacokinetic sampling was performed following each fuzuloparib dose. Safety and tolerability were assessed during the whole process via clinical laboratory tests. Ratios of least-squares means (GMRs) and 90% geometric confidence interval (90% CI) of maximum plasma concentration (Cmax), the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC0 − t) and the area under the curve of blood concentration from zero to infinity (AUC0−∞) for fuzuloparib combined with efavirenz to fuzuloparib alone were 0.473 (0.394, 0.568), 0.220 (0.185, 0.263) and 0.221 (0.185, 0.263), respectively. Co-administration with efavirenz led to 53% and 78% decreases in fuzuloparib Cmax and AUC0−∞. All 18 subjects enrolled in this study were included in the safety analysis set. A total of 16 subjects had 62 AEs during the study period. No serious adverse events (SAE) were reported. Most treatment-emergent adverse events were grade 1 or 2 based on CTCAE. Only one grade 3 adverse event was observed. Concomitant intake of fuzuloparib with the moderate CYP3A inhibitor efavirenz resulted in a decrease in fuzuloparib AUC0−∞ and Cmax of 78% and 53% respectively. The results suggested that concomitant moderate CYP3A inducers should be avoided during the administration of fuzuloparib, or else the dosage adjustments should be required. (This trial was registered athttp://www.chinadrugtrials.org.cn. The registration No. is CTR20211022, and the date of registration is 2021-05-13). pubtype: Academic Journal doctype: clinical trial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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