A phase 1 study of the safety, tolerability, pharmacodynamics, and pharmacokinetics of tenapanor in healthy Japanese volunteers

@article{Johansson2016AP1,
  title={A phase 1 study of the safety, tolerability, pharmacodynamics, and pharmacokinetics of tenapanor in healthy Japanese volunteers},
  author={Susanne Johansson and David P Rosenbaum and Mikael Knutsson and Maria Leonsson-Zachrisson},
  journal={Clinical and Experimental Nephrology},
  year={2016},
  volume={21},
  pages={407 - 416}
}
BackgroundTenapanor (RDX5791, AZD1722), a small molecule with minimal systemic availability, is an inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3). Tenapanor acts locally in the gut to reduce absorption of sodium and phosphate. It is being developed for the treatment of patients with hyperphosphatemia in CKD requiring dialysis and patients with constipation-predominant irritable bowel syndrome. We report the safety, pharmacodynamics, and pharmacokinetics of tenapanor in Japanese… Expand

Paper Mentions

Interventional Clinical Trial
The study is designed to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of AZD1722 in healthy Japanese subjects at increasing doses given for 7 days in… Expand
ConditionsHealthy Volunteer
InterventionDrug
Pharmacodynamics, Safety, and Tolerability of the NHE3 Inhibitor Tenapanor: Two Trials in Healthy Volunteers
TLDR
Tenapanor was well tolerated and resulted in reduced intestinal sodium absorption and softer stool consistency versus placebo, and potential use of tenapanor in patients who could benefit from modification of gastrointestinal sodium balance is supported. Expand
Effect of Food Intake on the Pharmacodynamics of Tenapanor: A Phase 1 Study
TLDR
The data suggest the effect of tenapanor on sodium absorption is most pronounced when administered before meals, whereas the effect on phosphate is similar whether administered before or after meals, which may support different timings ofTenapanor administration with respect to food for sodium‐ and phosphate‐related indications. Expand
Preclinical and Healthy Volunteer Studies of Potential Drug–Drug Interactions Between Tenapanor and Phosphate Binders
TLDR
The results suggest that the binding between sevelamer and tenapanor observed in vitro does not translate into altered pharmacodynamic effects in humans. Expand
Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial.
TLDR
Tenapanor significantly reduced elevated serum phosphate in patients with hyperphosphatemia receiving maintenance hemodialysis, and showed a significant benefit over placebo during the withdrawal period. Expand
Tenapanor administration and the activity of the H+‐coupled transporter PepT1 in healthy volunteers
TLDR
It is suggested that tenapanor 15 mg twice daily does not have a clinically relevant impact on the activity of the H+‐coupled transporter PepT1 in humans, and this may guide future research on drug–drug interactions involving NHE3 inhibitors. Expand
Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis.
TLDR
Tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis, and diarrhea was the most common adverse event. Expand
Effects of Tenapanor on Cytochrome P450‐Mediated Drug‐Drug Interactions
TLDR
It is suggested that tenapanor can be coadministered with CYP3A4‐metabolized drugs without affecting their exposure and found findings were similar for metabolites of midazolam. Expand
Therapeutic Effects of Add-On Tenapanor for Hemodialysis Patients with Refractory Hyperphosphatemia
TLDR
Therapy with existing phosphate binders and add-on tenapanor resulted in a significant decrease in serum phosphorus level compared with the placebo group in patients with refractory hyperphosphatemia despite treatment with phosphate binder. Expand
Tenapanor Treatment of Patients With Constipation-Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo-Controlled Efficacy and Safety Trial
TLDR
Tenapanor 50 mg b.i.d. significantly increased stool frequency and reduced abdominal symptoms in patients with IBS-C, and further research into tenapanor as a potential treatment for these patients is justified. Expand
The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia
TLDR
Following a marked increase in serum FGF23 in response to withdrawal of phosphate binders, tenapanor significantly decreased serum F GF23 in patients receiving hemodialysis with hyperphosphatemia. Expand
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