Evidence map›Paper›PMID 38424308›Full record

ArticleClinical pharmacokinetics2024

Clinical Evaluation of the Effect of Encorafenib on Bupropion, Rosuvastatin, and Coproporphyrin I and Considerations for Statin Coadministration.

Joseph Piscitelli, Micaela B Reddy, Lance Wollenberg, Laurence Del Frari, Jason Gong, Linda Wood, Yizhong Zhang, Kyle Matschke, Jason H Williams

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03864042 (An Open-label Phase 1 Study to Evaluate Drug-Drug Interactions of Agents Co-Administered With Encorafenib and Binimetinib in Patients With BRAF V600-mutant Unresectable or Metastatic Melanoma or Other Advanced Solid Tumors), which is not on this map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 20% 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.

NCT03864042 phase1completednot on this map

An Open-label Phase 1 Study to Evaluate Drug-Drug Interactions of Agents Co-Administered With Encorafenib and Binimetinib in Patients With BRAF V600-mutant Unresectable or Metastatic Melanoma or Other Advanced Solid Tumors

TypeinterventionalSponsorPfizerRan2018 to 2023Enrolled56ConditionsAdvanced Solid Tumors, Metastatic MelanomaArmslosartan, dextromethorphan, caffeine, omeprazole, midazolam
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. 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

9 authors at 2 institutions in 2 countries.

Joseph PiscitelliPfizer Inc, San Diego, CA, USA.ORCID 0009-0009-1174-966X
Micaela B ReddyPfizer Inc, Boulder, CO, USA.
Lance WollenbergPfizer Inc, Boulder, CO, USA.
Laurence Del FrariPierre Fabre Medicament, Toulouse, France.
Jason GongPfizer Inc, New York, NY, USA.
Linda WoodPfizer Inc, Groton, CT, USA.
Yizhong ZhangPfizer Inc, Groton, CT, USA.
Kyle MatschkePfizer Inc, Collegeville, PA, USA.
Jason H WilliamsPfizer Inc, San Diego, CA, USA. jason.williams@pfizer.com.
Pfizer (United States) · USPierre Fabre (France) · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesEncorafenib is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma or metastatic colorectal cancer, respectively, with selected BRAF V600 mutations. A clinical drug-drug interaction (DDI) study was designed to evaluate the effect of encorafenib on rosuvastatin, a sensitive substrate of OATP1B1/3 and breast cancer resistance protein (BCRP), and bupropion, a sensitive CYP2B6 substrate. Coproporphyrin I (CP-I), an endogenous substrate for OATP1B1, was measured in a separate study to deconvolute the mechanism of transporter DDI.

methodsDDI study participants received a single oral dose of rosuvastatin (10 mg) and bupropion (75 mg) on days - 7, 1, and 14 and continuous doses of encorafenib (450 mg QD) and binimetinib (45 mg BID) starting on day 1. The CP-I data were collected from participants in a phase 3 study who received encorafenib (300 mg QD) and cetuximab (400 mg/m

resultsBupropion exposure was not increased, whereas rosuvastatin C

conclusionThe results from these clinical studies suggest that encorafenib does not cause clinically relevant CYP2B6 induction or inhibition but is an inhibitor of BCRP and may also inhibit OATP1B1/3 to a lesser extent. Based on these results, it may be necessary to consider switching statins or reducing statin dosage accordingly for coadministration with encorafenib. CLINICAL

trial registrationClinicalTrials.gov NCT03864042, registered 6 March 2019.

Indexed as

BupropionCarbamatesCoproporphyrinsDrug InteractionsHydroxymethylglutaryl-CoA Reductase InhibitorsRosuvastatin CalciumSulfonamidesAdultAgedAged, 80 and overATP Binding Cassette Transporter, Subfamily G, Member 2FemaleHumansLiver-Specific Organic Anion Transporter 1MaleMiddle AgedATP Binding Cassette Transporter, Subfamily G, Member 2BupropionCarbamatescoproporphyrin ICoproporphyrinsencorafenibHydroxymethylglutaryl-CoA Reductase InhibitorsLiver-Specific Organic Anion Transporter 1Rosuvastatin CalciumSLCO1B1 protein, humanSulfonamides

Identifiers

PMID38424308
PMCPMC11052825
OpenAlexW4392282438

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.