Evidence map›Paper›PMID 26689566›Full record

ArticleDrugs in R&D2016

Effect of Food on the Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib (MLN8237) in Patients with Advanced Solid Tumors.

Gerald S Falchook, Xiaofei Zhou, Karthik Venkatakrishnan, Razelle Kurzrock, Devalingam Mahalingam, Jonathan W Goldman, JungAh Jung, Claudio Dansky Ullmann, Catherine Milch, Lee S Rosen and 1 more

Registry-linked trialAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Drugs in R&D, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00962091 (An Open-label, Phase 1 Study of the Relative Bioavailability, Food Effect, Safety and Tolerability of MLN8237 in Patients With Advanced Solid Tumors), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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.

NCT00962091 phase1completednot on this map

An Open-label, Phase 1 Study of the Relative Bioavailability, Food Effect, Safety and Tolerability of MLN8237 in Patients With Advanced Solid Tumors

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2009 to 2014Enrolled53ConditionsAdvanced Solid TumorsArmsAlisertib
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. The role of Aurora-A in human cancers and future therapeutics.American journal of cancer research · 2020
    Review
  4. Article
  5. New drugs in prostate cancer.Prostate international · 2016
    Review
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

11 authors.

Gerald S FalchookSarah Cannon Research Institute at HealthONE, Denver, CO, USA.
Xiaofei ZhouClinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA, 02139, USA. xiaofei.zhou@takeda.com.
Karthik VenkatakrishnanClinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA, 02139, USA.
Razelle KurzrockThe University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
Devalingam MahalingamInstitute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center, San Antonio, TX, USA.
Jonathan W GoldmanUniversity of California, Los Angeles, Santa Monica, CA, USA.
JungAh JungClinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA, 02139, USA.
Claudio Dansky UllmannInfinity Pharmaceuticals, Cambridge, MA, 02139, USA.
Catherine MilchClinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA, 02139, USA.
Lee S RosenUniversity of California, Los Angeles, Santa Monica, CA, USA.
John SarantopoulosInstitute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center, San Antonio, TX, USA.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lei Zheng · 1991 to 2026
$59.1M
U OF TEXAS HLTH SCI CTR HOUSTON CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCESUL1RR024148 · NCRR · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2006 to 2010
$27.9M
NCI NIH HHS CA016672NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA054174NCI NIH HHS P30CA054174NCRR NIH HHS UL1 RR024148
6 · The paper itself

Abstract

objectiveThis study was conducted to characterize the effects of food on single-dose pharmacokinetics (PK) of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors.

methodsFollowing overnight fasting for 10 h, a single 50 mg enteric-coated tablet (ECT) of alisertib was administered under either fasted (alisertib with 240 mL of water) or fed (high-fat meal consumed 30 min before receiving alisertib with 240 mL of water) conditions using a two-cycle, two-way crossover design. Patients on both arms were not allowed food for 4 h post-dose. Water was allowed as desired, except for 1 h before and after alisertib administration.

resultsTwenty-four patients were enrolled and 14 patients were PK-evaluable (ten patients were not PK-evaluable due to insufficient data). Following a single oral dose of alisertib, median t max was 6 h and 3 h under fed and fasted conditions, respectively. The geometric mean ratio of AUCinf (fed- vs. fasted-state dosing) was 0.94 [90% confidence interval (CI) 0.68-1.32]. The geometric mean C max under fed conditions was 84% of that under fasted conditions (90% CI 66-106). Alisertib was generally well-tolerated; most common drug-related grade 3/4 adverse events included neutropenia (50%), leukopenia (38%), and thrombocytopenia (21%).

conclusionsSystemic exposures achieved following a single 50 mg dose of alisertib administered as an ECT formulation after a high-fat meal are similar to those observed in the fasted state. Alisertib 50 mg ECT can be administered without regard for food. CLINICALTRIALS. GOV IDENTIFIER: NCT00962091.

Indexed as

Food-Drug InteractionsAdultAgedAntineoplastic AgentsAurora Kinase AAzepinesCross-Over StudiesDose-Response Relationship, DrugFemaleHumansMaleMaximum Tolerated DoseMiddle AgedNeoplasmsProtein Kinase InhibitorsPyrimidinesAntineoplastic AgentsAurora Kinase AAzepinesMLN 8237Protein Kinase InhibitorsPyrimidines

Identifiers

PMID26689566
PMCPMC4767718

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Registered trials

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.