Evidence map›Paper›PMID 27654985›Full record

ArticleClinical pharmacology in drug development2017

Preclinical and Healthy Volunteer Studies of Potential Drug-Drug Interactions Between Tenapanor and Phosphate Binders.

Susanne Johansson, Maria Leonsson-Zachrisson, Mikael Knutsson, Andrew G Spencer, Eric D Labonté, Desiree Deshpande, Jill Kohler, Kenji Kozuka, Dominique Charmot, David P Rosenbaum

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacology in drug development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02346890 (A Phase 1, Single-center, Randomized, 2-way Crossover, Open Label Study to Evaluate the Effect of Renvela on the Pharmacodynamics of AZD1722 in Healthy Volunteeers), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 17% 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.

NCT02346890 phase1completednot on this map

A Phase 1, Single-center, Randomized, 2-way Crossover, Open Label Study to Evaluate the Effect of Renvela on the Pharmacodynamics of AZD1722 in Healthy Volunteeers

TypeinterventionalSponsorArdelyxRan2013 to 2013Enrolled16ConditionsHealthyArmsAZD1722, Renvela
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 18 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis.Journal of the American Society of Nephrology : JASN · 2017
    Trial
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. 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

10 authors at 2 institutions in 2 countries.

Susanne JohanssonAstraZeneca Gothenburg, Mölndal, Sweden.
Maria Leonsson-ZachrissonAstraZeneca Gothenburg, Mölndal, Sweden.
Mikael KnutssonAstraZeneca Gothenburg, Mölndal, Sweden.
Andrew G SpencerFormerly of Ardelyx Inc., Fremont, CA, USA.
Eric D LabontéFormerly of Ardelyx Inc., Fremont, CA, USA.
Desiree DeshpandeFormerly of Ardelyx Inc., Fremont, CA, USA.
Jill KohlerArdelyx Inc., Fremont, CA, USA.
Kenji KozukaArdelyx Inc., Fremont, CA, USA.
Dominique CharmotFormerly of Ardelyx Inc., Fremont, CA, USA.
David P RosenbaumArdelyx Inc., Fremont, CA, USA.
Ardelyx (United States) · USAstraZeneca (Sweden) · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tenapanor (RDX5791, AZD1722), a first-in-class small molecule with minimal systemic availability, is an inhibitor of the sodium/hydrogen exchanger isoform 3. Tenapanor acts locally in the gut, where it reduces absorption of sodium and phosphate. It is being studied in patients with chronic kidney disease requiring dialysis, who are often administered phosphate binders such as sevelamer to help control hyperphosphatemia. We investigated whether coadministration of tenapanor with phosphate binders (sevelamer or calcium-based binders) impacts the pharmacodynamic effects of tenapanor. In vitro studies suggested a binding interaction between tenapanor and sevelamer, but this did not translate into altered pharmacodynamic effects in rats. An open-label, 2-way crossover study was then conducted in healthy volunteers (NCT02346890). This showed that 4 days' treatment with tenapanor hydrochloride (15 mg twice daily) with or without sevelamer carbonate (800 mg 3 times daily) resulted in comparable 24-hour stool and urinary sodium and phosphorus levels. Stool frequency, consistency, and weight were also comparable between the treatments. These results suggest that the binding between sevelamer and tenapanor observed in vitro does not translate into altered pharmacodynamic effects in humans.

Indexed as

AdultAnimalsCross-Over StudiesDrug Administration ScheduleDrug Evaluation, PreclinicalDrug InteractionsFemaleHealthy VolunteersHumansIsoquinolinesMaleMiddle AgedPhosphorusRandom AllocationRatsSevelamerIsoquinolinesPhosphorusSevelamerSodiumSulfonamidestenapanorchronic kidney diseasedrug-drug interactionshyperphosphatemiasodium absorptiontenapanor

Identifiers

PMID27654985
PMCPMC5599948
OpenAlexW2543318162

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.