Evidence map›Paper›PMID 25917876›Full record

Trial reportClinical pharmacokinetics2015

Clinical Pharmacokinetic Studies of Enzalutamide.

Jacqueline A Gibbons, Taoufik Ouatas, Walter Krauwinkel, Yoshiaki Ohtsu, Jan-Stefan van der Walt, Vanessa Beddo, Michiel de Vries, Joyce Mordenti

Open access · hybridAbstract readClinical Trial, Phase IClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical pharmacokinetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
9.3field-weighted citation impact, top 2% 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

61 citing papers in PubMed, 134 citations in OpenAlex.

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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 4 countries.

Jacqueline A GibbonsMedivation, Inc., 36th Floor, 525 Market Street, San Francisco, CA, 94105, USA. jackie.gibbons@medivation.com.
Taoufik OuatasAstellas Pharma Europe B.V., Leiden, The Netherlands.
Walter KrauwinkelAstellas Pharma Europe B.V., Leiden, The Netherlands.
Yoshiaki OhtsuAstellas Pharma Inc., Osaka, Japan.
Jan-Stefan van der WaltAstellas Pharma Europe B.V., Leiden, The Netherlands.
Vanessa BeddoICON Clinical Research, Durham, NC, USA.
Michiel de VriesAstellas Pharma Europe B.V., Leiden, The Netherlands.
Joyce MordentiMedivation, Inc., 36th Floor, 525 Market Street, San Francisco, CA, 94105, USA.
Astellas Pharma (Netherlands) · NLAstellas Pharma (Japan) · JPPinnacle Clinical Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesOral enzalutamide (160 mg once daily) is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This article describes the pharmacokinetics of enzalutamide and its active metabolite N-desmethyl enzalutamide.

methodsResults are reported from five clinical studies.

resultsIn a dose-escalation study (n = 140), enzalutamide half-life was 5.8 days, steady state was achieved by day 28, accumulation was 8.3-fold, exposure was approximately dose proportional from 30-360 mg/day, and intersubject variability was ≤30 %. In a mass balance study (n = 6), enzalutamide was primarily eliminated by hepatic metabolism. Renal excretion was an insignificant elimination pathway for enzalutamide and N-desmethyl enzalutamide. In a food-effect study (n = 60), food did not have a meaningful effect on area under the plasma concentration-time curve (AUC) of enzalutamide or N-desmethyl enzalutamide, and in an hepatic impairment study, AUC of the sum of enzalutamide plus N-desmethyl enzalutamide was similar in men with mild (n = 6) or moderate (n = 8) impairment (Child-Pugh Class A and B) versus men with normal hepatic function (n = 14). In a phase III trial, an exposure-response analysis of steady-state predose (trough) concentrations (C trough) versus overall survival (n = 1103) showed that active treatment C trough quartiles for 160 mg/day were uniformly beneficial relative to placebo, and no threshold of C trough was associated with a statistically significant better response.

conclusionsEnzalutamide has predictable pharmacokinetics, with low intersubject variability. Similar efficacy was observed in patients across the concentration/exposure range associated with a fixed oral dose of enzalutamide 160 mg/day.

Indexed as

AdultAgedAged, 80 and overAntineoplastic AgentsBenzamidesBiotransformationDose-Response Relationship, DrugDrug Administration ScheduleFood-Drug InteractionsHumansMaleMiddle AgedNitrilesPhenylthiohydantoinProstatic Neoplasms, Castration-ResistantAntineoplastic AgentsBenzamidesenzalutamideNitrilesPhenylthiohydantoin

Identifiers

PMID25917876
PMCPMC4580721
OpenAlexW2012639572

What OpenQuestion holds

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LicenceCC BY-NC
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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.