Evidence map›Paper›PMID 30845347›Full record

ArticleBritish journal of clinical pharmacology2019

Effect of CYP3A inhibitors on the pharmacokinetics of pevonedistat in patients with advanced solid tumours.

Hélène Faessel, John Nemunaitis, Todd M Bauer, A Craig Lockhart, Douglas V Faller, Farhad Sedarati, Xiaofei Zhou, Karthik Venkatakrishnan, R Donald Harvey

Open access · hybridAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Hélène FaesselMillennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.ORCID 0000-0002-3007-3345
John NemunaitisUniversity of Toledo, Toledo, OH, USA.
Todd M BauerSarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA.
A Craig LockhartSylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
Douglas V FallerMillennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Farhad SedaratiMillennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Xiaofei ZhouMillennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Karthik VenkatakrishnanMillennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.ORCID 0000-0003-4039-9813
R Donald HarveyWinship Cancer Institute, Emory University, Atlanta, GA, USA.
Takeda (United States) · USEmory University · USSarah Cannon · USUniversity of Miami · USUniversity of Toledo · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThis phase I study evaluated the effects of the moderate cytochrome P450 (CYP) 3A inhibitor fluconazole and the strong CYP3A/P-glycoprotein (P-gp) inhibitor itraconazole on the pharmacokinetics of the investigational neural precursor cell expressed, developmentally downregulated 8 (NEDD8)-activating enzyme inhibitor pevonedistat in patients with advanced solid tumours.

methodsPatients received single doses of intravenous pevonedistat 8 mg m

resultsThe ratios of geometric mean area under the concentration-time curves (n; 90% confidence interval) of pevonedistat in the presence vs. absence of fluconazole or itraconazole were 1.11 (12; 1.03-1.19) and 1.14 (33; 1.07-1.23), respectively. Fifty patients (98%) experienced at least one adverse event (AE), with maximum severity of grade 1-2 in 28 patients (55%) and of grade ≥3 in 22 patients (43%). The most common drug-related AEs were vomiting (12%), diarrhoea (10%) and nausea (8%). No new safety findings were observed for pevonedistat.

conclusionsFluconazole or itraconazole had insignificant effects on pevonedistat pharmacokinetics, indicating minor contributions of CYP3A/P-gp to pevonedistat clearance. The safety profile of single doses of pevonedistat plus steady-state fluconazole or itraconazole was consistent with prior clinical experience, with no new safety signals observed.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveCarboplatinCyclopentanesCytochrome P-450 CYP3A InhibitorsDocetaxelDrug InteractionsEnzyme InhibitorsFemaleFluconazoleHumansItraconazoleMaleCarboplatinCyclopentanesCytochrome P-450 CYP3A InhibitorsDocetaxelEnzyme InhibitorsFluconazoleItraconazolePaclitaxelpevonedistatPyrimidinesanticancer drugsdrug interactionspatient safetypharmacokinetics

Identifiers

PMID30845347
PMCPMC6595297
OpenAlexW2921688677

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.