Evidence map›Paper›PMID 33733338›Full record

Trial reportThe AAPS journal2021

Parent and Metabolite Concentration-QT Modeling to Evaluate QT-Interval Prolongation at Savolitinib Therapeutic Doses.

Stein Schalkwijk, Tarjinder Sahota, Remy B Verheijen, Alexander R Harmer, Ghada F Ahmed

Abstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The AAPS journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
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

5 authors.

Stein SchalkwijkBioPharmaceuticals R&D, Clinical Pharmacology and Safety Sciences, AstraZeneca, Cambridge, UK. stein.schalkwijk@astrazeneca.com.
Tarjinder SahotaFormerly BioPharmaceuticals R&D, Clinical Pharmacology and Safety Sciences, AstraZeneca, Cambridge, UK.
Remy B VerheijenFormerly, Oncology R&D, AstraZeneca, Cambridge, UK.
Alexander R HarmerFunctional and Mechanistic Safety, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK.
Ghada F AhmedFormerly BioPharmaceuticals R&D, Clinical Pharmacology and Safety Sciences, AstraZeneca, Cambridge, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Savolitinib is an oral, potent, and highly selective MET-tyrosine kinase inhibitor under investigation in various tumor types. A thorough QT study evaluated effects on QT interval after a 600-mg single savolitinib dose in healthy subjects. We report exposure-response (E-R) modeling from this study to characterize the effects of savolitinib and its metabolites, M2 and M3, on QTc changes. In a novel application, in vitro potencies against hERG current provided mechanistic support to model the metabolites' effects. The hERG IC50 estimates (95% CI) were 25.8 (22.2-29.9) and 22.6 (14.7-34.6) μM for parent and M2, respectively. The E-R was described by both linear and E

Indexed as

Models, BiologicalDouble-Blind MethodElectrocardiographyHealthy VolunteersHeart RateHumansInhibitory Concentration 50Long QT SyndromeMaleMiddle AgedProtein Kinase InhibitorsPyrazinesTriazines1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazineProtein Kinase InhibitorsPyrazinesTriazinesconcentration-QT modelinghERG activityparent-metabolite QTQT intervalsavolitinib

Identifiers

PMID33733338

What OpenQuestion holds

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Registered trials

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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.