Evidence map›Paper›PMID 26238121›Full record

Trial reportNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2015

Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients.

Anatole Besarab, Robert Provenzano, Joachim Hertel, Raja Zabaneh, Stephen J Klaus, Tyson Lee, Robert Leong, Stefan Hemmerich, Kin-Hung Peony Yu, Thomas B Neff

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

Trial report in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00761657 (A Randomized, Single-blind, Placebo-controlled, 4-Week Treatment Study of the Safety and Biologic Activity of Escalating Multiple Oral Doses of FG-4592 in Subjects With Chronic Kidney Disease Not Requiring Dialysis), which is not on this map. Cited by 149 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 18 pooled it
–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.

NCT00761657 phase2completednot on this map

A Randomized, Single-blind, Placebo-controlled, 4-Week Treatment Study of the Safety and Biologic Activity of Escalating Multiple Oral Doses of FG-4592 in Subjects With Chronic Kidney Disease Not Requiring Dialysis

TypeinterventionalSponsorKyntra BioRan2006 to 2010Enrolled117ConditionsChronic Kidney Disease, AnemiaArmsRoxadustat, Placebo
3 · Its place in the literature

Who cites it

149 citing papers in PubMed, 18 syntheses or guidelines pooled it.

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89 more citing papers are in PubMed but not listed here.

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

10 authors.

Anatole BesarabFibroGen, Inc., San Francisco, CA, USA.
Robert ProvenzanoSt Clair Specialty Physicians, Detroit, MI, USA.
Joachim HertelKidney Care Associates, LLC, Augusta, GA, USA.
Raja ZabanehNorthwest Louisiana Nephrology, Shreveport, LA, USA.
Stephen J KlausFibroGen, Inc., San Francisco, CA, USA.
Tyson LeeFibroGen, Inc., San Francisco, CA, USA.
Robert LeongFibroGen, Inc., San Francisco, CA, USA.
Stefan HemmerichFibroGen, Inc., San Francisco, CA, USA.
Kin-Hung Peony YuFibroGen, Inc., San Francisco, CA, USA.
Thomas B NeffFibroGen, Inc., San Francisco, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRoxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. This Phase 2a study tested efficacy (Hb response) and safety of roxadustat in anemic nondialysis-dependent chronic kidney disease (NDD-CKD) subjects.

methodsNDD-CKD subjects with hemoglobin (Hb) ≤11.0 g/dL were sequentially enrolled into four dose cohorts and randomized to roxadustat or placebo two times weekly (BIW) or three times weekly (TIW) for 4 weeks, in an approximate roxadustat:placebo ratio of 3:1. Efficacy was assessed by (i) mean Hb change (ΔHb) from baseline (BL) and (ii) proportion of Hb responders (ΔHb ≥ 1.0 g/dL). Pharmacodynamic evaluation was performed in a subset of subjects. Safety was evaluated by adverse event frequency/severity.

resultsOf 116 subjects receiving treatment, 104 completed 4 weeks of dosing and 96 were evaluable for efficacy. BL characteristics for roxadustat and placebo groups were comparable. In roxadustat-treated subjects, Hb levels increased from BL in a dose-related manner in the 0.7, 1.0, 1.5 and 2.0 mg/kg groups. Maximum ΔHb within the first 6 weeks was significantly higher in the 1.5 and 2.0 mg/kg groups than in the placebo subjects. Hb responder rates were dose dependent and ranged from 30% in the 0.7 mg/kg BIW group to 100% in the 2.0 mg/kg BIW and TIW groups versus 13% in placebo.

conclusionsRoxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin. Adverse events were similar in the roxadustat and placebo groups. Roxadustat produced dose-dependent increases in blood Hb among anemic NDD-CKD patients in a placebo-controlled trial. CLINICAL TRIALS REGISTRATION: Clintrials.gov #NCT00761657.

Indexed as

AdolescentAdultAgedAged, 80 and overAnemiaCohort StudiesDose-Response Relationship, DrugErythropoiesisErythropoietinFemaleGlycineHemoglobinsHepcidinsHumansHypoxia-Inducible Factor-Proline DioxygenasesIsoquinolinesErythropoietinGlycineHemoglobinsHepcidinsHypoxia-Inducible Factor-Proline DioxygenasesIsoquinolinesroxadustatanemiachronic kidney diseaseerythropoietinhepcidinHIF-PHI

Identifiers

PMID26238121
PMCPMC4569392

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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.