Evidence map›Paper›PMID 41703907›Full record

ArticleBritish journal of clinical pharmacology2026

Effect of carbamazepine on the pharmacokinetics of vepdegestrant, a PROteolysis TArgeting Chimera estrogen receptor degrader, in healthy adults.

Hechuan Wang, Jennifer A Winton, Kyle T Matschke, Alexandre Stouffs, Kimberly C Lee, Yuanyuan Zhang, Wenlian Qiao, Weiwei Tan

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

Article in British journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06005688 (An Interventional, Phase 1, Open-Label, Fixed Sequence, 2-Period Study to Estimate the Effect of Multiple Doses of Carbamazepine on the Pharmacokinetics of Single Dose Vepdegestrant), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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.

NCT06005688 phase1completednot on this map

An Interventional, Phase 1, Open-Label, Fixed Sequence, 2-Period Study to Estimate the Effect of Multiple Doses of Carbamazepine on the Pharmacokinetics of Single Dose Vepdegestrant (ARV-471, PF-07850327) 200 mg Under the Fed Condition in Healthy Adult Males and Females of Nonchildbearing Potential

TypeinterventionalSponsorPfizerRan2023 to 2023Enrolled12ConditionsHealthy ParticipantsArmsVepdegestrant, Carbamazepine
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. 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

8 authors.

Hechuan WangPfizer, Inc., La Jolla, California, USA.ORCID https://orcid.org/0000-0002-0792-7816
Jennifer A WintonPfizer, Inc., Groton, Connecticut, USA.
Kyle T MatschkePfizer, Inc., Collegeville, Pennsylvania, USA.
Alexandre StouffsPfizer Clinical Research Unit, Brussels, Belgium.ORCID https://orcid.org/0000-0001-5865-0485
Kimberly C LeePfizer, Inc., Groton, Connecticut, USA.
Yuanyuan ZhangArvinas Operations, Inc., New Haven, Connecticut, USA.
Wenlian QiaoPfizer, Inc., La Jolla, California, USA.
Weiwei TanPfizer, Inc., La Jolla, California, USA.ORCID https://orcid.org/0000-0001-8915-1152

Funding

Arvinas Estrogen Receptor, Inc.Pfizer, Inc.
6 · The paper itself

Abstract

aimTo evaluate the effects of carbamazepine, a strong cytochrome P450 (CYP)3A4 inducer, on the pharmacokinetics and safety of vepdegestrant, a PROteolysis TArgeting Chimera estrogen receptor degrader.

methodsThis was a phase 1, open-label, fixed-sequence, two-period study in healthy adult participants. During Period 1, a single oral dose of vepdegestrant 200 mg was administered (Day 1). During Period 2, carbamazepine dosing was titrated from 200 mg orally once daily (Days 1-3) to twice (Days 4-7) and three times daily (Days 8-19); a single oral dose of vepdegestrant 200 mg was administered (Day 14). Blood samples for pharmacokinetics analysis were collected up to 144 h after dosing in both periods. Safety was monitored throughout the study.

resultsTwelve healthy male participants were enrolled and treated. Following administration of vepdegestrant with (test) and without (reference) carbamazepine, test/reference ratios (90% confidence intervals) of the adjusted geometric means for vepdegestrant area under the plasma concentration-time curve from time 0 to infinity and maximum plasma concentration were 64.1% (60.0% to 68.4%) and 80.2% (74.0% to 86.8%), respectively. Similar decreases in ARV-473 (vepdegestrant epimer) exposure were observed. Two participants discontinued during Period 2 due to elevated liver enzymes and maculopapular rash (both unrelated to vepdegestrant; one participant each).

conclusionCoadministration of multiple doses of carbamazepine 200 mg, a strong CYP3A4 inducer, with a single dose of vepdegestrant 200 mg resulted in a modest (36%) decrease in plasma vepdegestrant exposure. A single dose of vepdegestrant 200 mg was well tolerated in healthy adult participants. CLINICAL

trial registrationNCT06005688.

Indexed as

CarbamazepineCytochrome P-450 CYP3A InducersAdministration, OralAdultArea Under CurveCytochrome P-450 CYP3ADrug InteractionsHealthy VolunteersHumansMaleMiddle AgedProteolysis Targeting ChimeraYoung AdultCarbamazepineCYP3A4 protein, humanCytochrome P-450 CYP3ACytochrome P-450 CYP3A InducersProteolysis Targeting Chimeracytochrome P450 (pharmacokinetics)drug interactions (pharmacokinetics)oncology (breast cancer)phase I (drug development)

Identifiers

PMID41703907
PMCPMC13304248

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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.