Evidence map›Paper›PMID 39907965›Full record

ArticleClinical pharmacokinetics2025

Effect of Hepatic Impairment or Renal Impairment on the Pharmacokinetics of Aficamten.

Donghong Xu, Justin D Lutz, Punag Divanji, Jianlin Li, Youcef Benattia, Adrienne Griffith, Stephen B Heitner, Stuart Kupfer, Polina German

Erratum issuedAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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.

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

5 citing papers in PubMed.

  1. Trial
  2. Contractile effects of Aficamten in the human atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2026
    Article
  3. Review
  4. Review
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Donghong XuDepartment of Clinical Pharmacology, Cytokinetics, Incorporated, 350 Oyster Point Blvd, South San Francisco, CA, 94080, USA. dxu@cytokinetics.com.ORCID 0009-0000-9678-0133
Justin D LutzDepartment of Clinical Pharmacology, Cytokinetics, Incorporated, 350 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Punag DivanjiDepartment of Clinical Research, Cytokinetics, Incorporated, South San Francisco, CA, USA.
Jianlin LiDepartment of Clinical Biometrics, Cytokinetics, Incorporated, South San Francisco, CA, USA.
Youcef BenattiaDepartment of Drug Safety/Pharmacovigilance, Cytokinetics, Incorporated, South San Francisco, CA, USA.
Adrienne GriffithDepartment of Clinical Pharmacology, Cytokinetics, Incorporated, 350 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Stephen B HeitnerDepartment of Clinical Research, Cytokinetics, Incorporated, South San Francisco, CA, USA.ORCID 0000-0003-2189-1474
Stuart KupferDepartment of Clinical Administration, Cytokinetics, Incorporated, South San Francisco, CA, USA.ORCID 0000-0002-5469-1287
Polina GermanDepartment of Clinical Pharmacology, Cytokinetics, Incorporated, 350 Oyster Point Blvd, South San Francisco, CA, 94080, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveAficamten, a small-molecule, selective cardiac myosin inhibitor, is under development for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Aficamten is primarily eliminated by hepatic metabolism with renal excretion playing a minor role. The objective of this investigation was to evaluate the pharmacokinetics (PK) of aficamten in moderate hepatic impairment or mild to moderate renal impairment to inform dosing recommendations in HCM patients with mild or moderate hepatic impairment or mild to moderate renal impairment.

methodsThe impact of hepatic impairment on the PK of single-dose aficamten 20 mg was evaluated in a phase 1 single-dose, open-label, parallel-group study, in healthy participants with moderate (n = 8) hepatic impairment (Child-Pugh B classification) versus participants with normal hepatic function (n = 8). Safety was monitored throughout. The effect of renal impairment on aficamten PK was assessed using population PK (PopPK) modelling of phase 2/3 clinical data in patients with oHCM.

resultsAficamten PK was similar in participants with moderate hepatic impairment and those with normal hepatic function. No serious or severe treatment-emergent adverse events or clinically significant laboratory abnormalities were reported. There were no clinical meaningful differences in aficamten exposure in patients with oHCM with mild or moderate renal impairment and those with normal renal function.

conclusionsNo clinically relevant changes in aficamten PK were observed in participants with moderate hepatic impairment. Population PK analysis indicated mild or moderate renal impairment and had no statistically or clinically significant impact on aficamten PK in patients with oHCM. Aficamten dose adjustment may not be necessary in patients with mild or moderate hepatic or renal impairment.

Indexed as

Liver DiseasesPyrazolesRenal InsufficiencyAdultAgedCardiomyopathy, HypertrophicFemaleHumansMaleMiddle AgedModels, BiologicalYoung AdultaficamtenPyrazoles

Identifiers

PMID39907965
PMCPMC11954688

What Socratic holds

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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 Socratic graph.