Evidence map›Paper›PMID 36267872›Full record

ArticleJHEP reports : innovation in hepatology2022

Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis.

Christoph Schramm, Heiner Wedemeyer, Andrew Mason, Gideon M Hirschfield, Cynthia Levy, Kris V Kowdley, Piotr Milkiewicz, Ewa Janczewska, Elena Sergeevna Malova, Johanne Sanni and 6 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02516605 (A Multi-part, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Efficacy of Tropifexor), which is not on this map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
6.4field-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.

NCT02516605 phase2completednot on this map

A Multi-part, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Efficacy of Tropifexor (LJN452) in Patients With Primary Biliary Cholangitis

TypeinterventionalSponsorNovartis PharmaceuticalsRan2015 to 2018Enrolled61ConditionsPrimary Biliary CholangitisArmsPart 1: LJN452, Part 1: Placebo, Part 2: LJN452 Dose level 1, Part 2: Placebo, Part 2: LJN452 Dose level 2
3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

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  18. The gut microbiota-bile acid axis in cholestatic liver disease.Molecular medicine (Cambridge, Mass.) · 2024
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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

16 authors at 12 institutions in 7 countries.

Christoph SchrammMedizinische Klinik und Poliklinik Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany.
Heiner WedemeyerDepartment of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany.
Andrew MasonDivision of Gastroenterology, University of Alberta, Edmonton, AB, Canada.
Gideon M HirschfieldToronto Centre for Liver Disease, Department of Medicine, University of Toronto, Toronto, ON, Canada.
Cynthia LevyUniversity of Miami, Schiff Center for Liver Diseases, Miami, FL, USA.
Kris V KowdleyLiver Institute Northwest, Washington State University, Seattle, WA, USA.
Piotr MilkiewiczLiver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland.
Ewa JanczewskaID Clinic, Myslowice Poland.
Elena Sergeevna MalovaMedical Company Hepatolog, LLC, Samara, Russia.
Johanne SanniNovartis Institutes for Biomedical Research, Basel, Switzerland.
Phillip KooNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Jin ChenNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Subhajit ChoudhuryNovartis Healthcare Pvt. Ltd., Hyderabad, India.
Lloyd B KlicksteinNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Michael K BadmanNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
David JonesThe Newcastle Upon Tyne Hospitals, NHS Foundation Trust, Royal Victoria Infirmary, Newcastle, UK.
Novartis (United States) · USEssen University Hospital · DELiver Institute Northwest · USMedical University of Silesia · PLMedical University of Warsaw · PLNovartis (India) · INNovartis (Switzerland) · CHRoyal Victoria Infirmary · GBUniversität Hamburg · DEUniversity of Alberta · CAUniversity of Miami · USUniversity of Toronto · CA

Funding

Medical Research Council MR/L001489/1
6 · The paper itself

Abstract

Background & Aims: The safety, tolerability, and efficacy of the non-bile acid farnesoid X receptor agonist tropifexor were evaluated in a phase II, double-blind, placebo-controlled study as potential second-line therapy for patients with primary biliary cholangitis (PBC) with an inadequate ursodeoxycholic acid response. Methods: Patients were randomised (2:1) to receive tropifexor (30, 60, 90, or 150 μg) or matched placebo orally once daily for 28 days, with follow-up on Days 56 and 84. Primary endpoints were safety and tolerability of tropifexor and reduction in levels of γ-glutamyl transferase (GGT) and other liver biomarkers. Other objectives included patient-reported outcome measures using the PBC-40 quality-of-life (QoL) and visual analogue scale scores and tropifexor pharmacokinetics. Results: Of 61 enrolled patients, 11, 9, 12, and 8 received 30-, 60-, 90-, and 150-μg tropifexor, respectively, and 21 received placebo; 3 patients discontinued treatment because of adverse events (AEs) in the 150-μg tropifexor group. Pruritus was the most frequent AE in the study (52.5% [tropifexor] Conclusions: Tropifexor showed improvement in cholestatic markers relative to placebo, predictable pharmacokinetics, and an acceptable safety-tolerability profile, thereby supporting its potential further clinical development for PBC. Lay summary: The bile acid ursodeoxycholic acid (UDCA) is the standard-of-care therapy for primary biliary cholangitis (PBC), but approximately 40% of patients have an inadequate response to this therapy. Tropifexor is a highly potent non-bile acid agonist of the farnesoid X receptor that is under clinical development for various chronic liver diseases. In the current study, in patients with an inadequate response to UDCA, tropifexor was found to be safe and well tolerated, with improved levels of markers of bile duct injury at very low (microgram) doses. Itch of mild to moderate severity was observed in all groups including placebo but was more frequent at the highest tropifexor dose. Clinical Trials Registration: This study is registered at ClinicalTrials.gov (NCT02516605).

Indexed as

AE, adverse eventALP, alkaline phosphataseALT, alanine aminotransferaseAUC, area under the concentration–time curveC4, 7-alpha-hydroxy-4-cholesten-3-oneCL/F,ss, the apparent systemic clearance following oral administration at steady stateCmax, maximum plasma concentrationFarnesoid X receptorFGF19, fibroblast growth factor 19FXR, farnesoid X receptorGGT, γ-glutamyl transferaseHDL, high-density lipoproteinLDL, low-density lipoproteinNASH, non-alcoholic steatohepatitisOCA, obeticholic acidpBAD, primary bile acid diarrhoeaPBC, primary biliary cholangitisPD, pharmacodynamicPrimary biliary cholangitisProof of conceptPRO, patient-reported outcomePruritusqd, once dailyQoL, quality of lifeRacc, accumulation ratioSAE, serious adverse eventTmax, time to reach CmaxTropifexorULN, upper limit of normalVAS, visual analogue scaleγ-Glutamyl transferase

Identifiers

PMID36267872
PMCPMC9576902
OpenAlexW4286509886

What OpenQuestion holds

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LicenceCC BY
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.