Evidence map›Paper›PMID 27094945›Full record

Trial reportClinical rheumatology2016

Acute kidney injury observed during phase 1 clinical trials of a novel xanthine oxidase/URAT1 dual inhibitor PF-06743649.

Pinky Dua, Rachel Gurrell, Simon Kirby, Maria Sudworth, Peter T Loudon

Abstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Clinical rheumatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the 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
1.8field-weighted citation impact, top 16% 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.

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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Inhibitory effect ofNPJ science of food · 2020
    Article
  5. Review
  6. Review
  7. Lesinurad: what the nephrologist should know.Clinical kidney journal · 2017
    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

5 authors at 2 institutions in 1 country.

Pinky DuaPfizer Neuroscience and Pain Research Unit, The Portway Building, Granta Park, Cambridge, CB21 6GS, UK.
Rachel GurrellPfizer Neuroscience and Pain Research Unit, The Portway Building, Granta Park, Cambridge, CB21 6GS, UK.
Simon KirbyPfizer Neuroscience and Pain Research Unit, The Portway Building, Granta Park, Cambridge, CB21 6GS, UK.
Maria SudworthAdClinico Consulting Ltd, Hawks Barn, Dilnot Lane, Acol, CT7 0HW, UK.
Peter T LoudonPfizer Neuroscience and Pain Research Unit, The Portway Building, Granta Park, Cambridge, CB21 6GS, UK. peter.t.loudon@pfizer.com.
Pfizer (United Kingdom) · GBCD-adapco (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The objective of these clinical studies was to assess the safety and urate lowering activity of a novel urate transporter 1 (URAT1)/ xanthine oxidase (XO) inhibitor PF-06743649 in healthy subjects and gout patients. Escalating doses of PF-06743649 or placebo were given to healthy young subjects, healthy elderly subjects and gout patients. Serum uric acid (sUA) and urinary pharmacodynamic markers were assayed, and safety was assessed by collection of adverse events and assessment of safety labs, ECGs and vital signs. Administration of PF-06743649 led to rapid decrease in sUA in all cohorts; in gout patients, a change from baseline of 69 % was observed for the 40 mg dose. Urinary and serum biomarkers were consistent with inhibition of both URAT1 and XO. Although dosing was otherwise well tolerated, two subjects experienced serious adverse events of acute kidney injury. Both subjects exhibited increased serum creatinine and blood urea nitrogen in the first 3 days post first dose and were hospitalised. One subject exhibited oliguria for the first 24 h. Both subjects made a complete recovery with minimal intervention. PF-06743649 was effective at rapidly lowering sUA, but further development was terminated for an identified renal safety risk.

Indexed as

Acute Kidney InjuryAdolescentAdultAgedAged, 80 and overBiomarkersDouble-Blind MethodFemaleGoutGout SuppressantsHumansHyperuricemiaMaleMiddle AgedOrganic Anion TransportersOrganic Cation Transport ProteinsBiomarkersGout SuppressantsOrganic Anion TransportersOrganic Cation Transport ProteinsSLC22A12 protein, humanUric AcidXanthine OxidaseAcute kidney injuryGoutURAT1Xanthine oxidase

Identifiers

PMID27094945
OpenAlexW2339538813

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.