Pharmacokinetics and Safety of Amenamevir in Healthy Subjects: Analysis of Four Randomized Phase 1 Studies.
Introduction: Amenamevir (ASP2151) is a nonnucleoside antiherpesvirus compound available for the treatment of varicella-zoster virus infections. In this article we summarize the findings of four phase 1 studies in healthy participants.Methods: Four randomized phase 1 studies investigated the safety...
| Publicado en: | Advances in Therapy Vol. 34; no. 12; pp. 2625 - 2638 |
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| Autores principales: | , , , , , , , , |
| Formato: | clinical trial research randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Dec2017
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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=126486061&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 126486061 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0741238X 1XDX jtl: Advances in Therapy issn: 0741238X maglogo: N pubinfo: dt: Dec2017 vid: 34 iid: 12 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 126486061 126486061 144108399 NLM29134426 126486061 10.1007/s12325-017-0642-4 NLM29134426 126486061 ppf: 2625 ppct: 13 formats: tig: atl: Pharmacokinetics and Safety of Amenamevir in Healthy Subjects: Analysis of Four Randomized Phase 1 Studies. aug: au: Kusawake, Tomohiro Keirns, James Kowalski, Donna den Adel, Martin Groenendaal-van de Meent, Dorien Takada, Akitsugu Ohtsu, Yoshiaki Katashima, Masataka Keirns, James J affil: Astellas Pharma Global Development Inc. , Northbrook USA sug: subj: Antiviral Agents Pharmacokinetics Research Subjects Statistics and Numerical Data Antiviral Agents Therapeutic Use Heterocyclic Compounds Pharmacokinetics Herpes Zoster Drug Therapy Heterocyclic Compounds Therapeutic Use Dose-Response Relationship, Drug Adult Japan Middle Age Male Female Human Aged Crossover Design Clinical Trials Validation Studies Comparative Studies Evaluation Research Multicenter Studies Randomized Controlled Trials Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Male Female ab: Introduction: Amenamevir (ASP2151) is a nonnucleoside antiherpesvirus compound available for the treatment of varicella-zoster virus infections. In this article we summarize the findings of four phase 1 studies in healthy participants.Methods: Four randomized phase 1 studies investigated the safety and pharmacokinetics of single and multiple doses of amenamevir, including the assessment of age group effect (nonelderly vs elderly), food effect, and the relative bioavailability of two formulations. Amenamevir was administered orally at various doses as a single dose (5-2400 mg) or daily (300 or 600 mg/day) for 7 days.Results: Following single and multiple oral doses, amenamevir demonstrated a less than dose proportional increase in the pharmacokinetic parameters area under the plasma drug concentration versus time curve from time zero to infinity (AUCinf) and C max. After single and multiple oral 300-mg doses of amenamevir, no apparent differences in pharmacokinetics were observed between nonelderly and elderly participants. In contrast, with the amenamevir 600-mg dose both the area under the plasma drug concentration versus time curve from time zero to 24 h and C max were slightly increased and renal clearance was decreased in elderly participants. The pharmacokinetics of amenamevir was affected by food, with AUCinf increased by about 90%. In the bioavailability study, AUCinf and C max were slightly lower following tablet versus capsule administration (decreased by 14 and 12%, respectively), with relative bioavailability of 86%. The different amenamevir doses and formulations were safe and well tolerated; no deaths or serious adverse events were reported.Conclusion: Amenamevir had less than dose proportional pharmacokinetic characteristics. Age may have an influence on amenamevir pharmacokinetics; however, the effect was considered minimal. The pharmacokinetics of amenamevir were affected by food, with AUCinf almost doubling when amenamevir was administered with food. The concentration versus time profile of the tablet was slightly lower than that of the capsule; the relative bioavailability of the tablet versus the capsule was 86%. Amenamevir was safe and well tolerated in the dose range investigated.Funding: Astellas Pharma.Trial Registration: ClinicalTrials.gov identifiers NCT02852876 (15L-CL-002) and NCT02796118 (15L-CL-003). pubtype: Academic Journal doctype: clinical trial research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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