Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.
Purpose: To characterize the safety, pharmacodynamics, and pharmacokinetics (PK) of vericiguat in healthy males. Methods: Six phase I studies were conducted in European, Chinese, and Japanese males. Subjects received oral vericiguat as a single dose (0.5–15.0 mg solution [for first-in-human study] o...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 77; no. 4; pp. 527 - 538 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Apr2021
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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=149092709&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 149092709 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Apr2021 vid: 77 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 149092709 146726662 149092709 149092709 10.1007/s00228-020-03023-7 149092709 ppf: 527 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects. aug: au: Boettcher, Michael Thomas, Dirk Mueck, Wolfgang Loewen, Stephanie Arens, Erich Yoshikawa, Kenichi Becker, Corina affil: Research & Development, Pharmaceuticals, Clinical PD CV, Bayer AG, Wuppertal, Germany sug: subj: Heterocyclic Compounds Pharmacodynamics Heterocyclic Compounds Pharmacokinetics Patient Safety Random Assignment Randomized Controlled Trials Human Male Chinese Persons Japanese Persons Heterocyclic Compounds Administration and Dosage Biological Availability Heterocyclic Compounds Adverse Effects Confidence Intervals Descriptive Statistics Drug Tolerance Heart Failure Drug Therapy Male ab: Purpose: To characterize the safety, pharmacodynamics, and pharmacokinetics (PK) of vericiguat in healthy males. Methods: Six phase I studies were conducted in European, Chinese, and Japanese males. Subjects received oral vericiguat as a single dose (0.5–15.0 mg solution [for first-in-human study] or 1.25–10.0 mg immediate release [IR tablets]) or multiple doses (1.25–10.0 mg IR tablets once daily [QD] or 5.0 mg IR tablets twice daily for 7 consecutive days). Bioavailability and food effects on vericiguat PK (IR tablets) were also studied in European subjects. Results: Overall, 255 of 265 randomized subjects completed their respective studies. There were no deaths or serious adverse events. Vericiguat was generally well tolerated at doses ≤ 10.0 mg. In the first-in-human study, the most frequent drug-related adverse events were headache and postural dizziness (experienced by five subjects each [7.2%]). Three of four subjects who received vericiguat 15.0 mg (oral solution, fasted) experienced orthostatic reactions. Vericiguat (≤ 10.0 mg, IR tablets) was rapidly absorbed (median time to reach maximum plasma concentration ≤ 2.5 h [fasted]) with a mean half-life of about 22.0 h (range 17.9–27.0 h for single and multiple doses). No evidence for deviation from dose proportionality or unexpected accumulation was observed. Administration of vericiguat 5.0 mg IR tablets with food increased bioavailability by 19% (estimated ratio 119% [90% confidence interval]: 108; 131]), reduced PK variability, and prolonged vericiguat absorption relative to the fasted state. Conclusion: In general, vericiguat was well tolerated. These results supported further clinical evaluation of vericiguat QD in patients with heart failure. Registry numbers: EudraCT: 2011-001627-21; EudraCT: 2012-000953-30 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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