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Cited by 102Gastrointestinal motility and disordersInflammatory Bowel DiseasePelvic floor disorders treatments

Tenapanor Treatment of Patients With Constipation-Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo-Controlled Efficacy and Safety Trial

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Chey, William D, Lembo, Anthony J, Rosenbaum, David P·2017·American Journal of Gastroenterology
DOI 10.1038/ajg.2017.41PMC PMC5418559
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Abstract

OBJECTIVES: Tenapanor is a first-in-class, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger NHE3. This study assessed the efficacy and safety of tenapanor in patients with constipation-predominant irritable bowel syndrome (IBS-C). METHODS: In this phase 2, double-blind study, patients with IBS-C (Rome III criteria) were randomized (1:1:1:1) to receive tenapanor 5 mg, 20 mg, or 50 mg b.i.d., or placebo b.i.d. for 12 weeks. The primary end point was the complete spontaneous bowel movement (CSBM) responder rate, defined as the proportion of patients reporting an increase from baseline of ≥1 CSBM/week for ≥6/12 treatment weeks. Secondary end points included abdominal symptom responder rates (≥30% score improvement from baseline for ≥6/12 weeks) and a composite responder rate (CSBM and abdominal pain response in the same week for ≥6/12 weeks). RESULTS: Overall, 356 patients were randomized (mean age: 45.7 years; 86.8% women) and 304 completed the study. The CSBM responder rate was significantly higher in the tenapanor 50 mg b.i.d. group than in the placebo group (60.7 vs. 33.7%; P<0.001), as was the composite responder rate (50.0 vs. 23.6%; P<0.001). Responder rates for abdominal symptoms (pain, discomfort, bloating, cramping, and fullness) were significantly higher in the tenapanor 50 mg b.i.d. group than in the placebo group (all P<0.05). Diarrhea was the most frequent adverse event (tenapanor b.i.d.: 20 mg, 12.4%; 50 mg, 11.2%). CONCLUSIONS: Tenapanor 50 mg b.i.d. significantly increased stool frequency and reduced abdominal symptoms in patients with IBS-C. Further research into tenapanor as a potential treatment for these patients is justified.

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  • Placebo-controlled trials have demonstrated efficacy of intestinal secretagogues (lubiprostone, linaclotide, plecanatide, tenapanor) in IBS-C.

    “Placebo-controlled trials have demonstrated efficacy of these drugs in IBS-C”

    From Irritable bowel syndrome (2020) · cites this paper as [116]

    The Introduction (page unavailable) reports that linaclotide and lubiprostone outperformed placebo in randomized trials, and the Discussion (page unavailable) reports that tenapanor 50 mg twice daily significantly outperformed placebo in this trial. The copy does not establish placebo-controlled efficacy for plecanatide, so it does not support the claim for all four named drugs. (LLM, conf=0.88)

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Research works printed but not linked: 19

  1. Longstreth GF, Thompson WG, Chey WD et al. Functional bowel disorders. Gastroenterology 2006; 130: 1480–1491. 16678561
  2. Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol 2014; 6: 71–80. 24523597 PMC3921083
  3. Pare P, Gray J, Lam S et al. Health-related quality of life, work productivity, and health care resource utilization of subjects with irritable bowel syndrome: baseline results from LOGIC (Longitudinal Outcomes Study of Gastrointestinal Symptoms in Canada), a naturalistic study. Clin Ther 2006; 28: 1726–1735. 17157129
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  6. Lacy BE, Chey WD, Lembo AJ. New and emerging treatment options for irritable bowel syndrome. Gastroenterol Hepatol (N Y) 2015; 11: 1–19. PMC4612133 26491416
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  8. Quigley EM, Tack J, Chey WD et al. Randomised clinical trials: linaclotide phase 3 studies in IBS-C—a prespecified further analysis based on European Medicines Agency-specified endpoints. Aliment Pharmacol Ther 2013; 37: 49–61. 23116208
  9. Chey WD, Lembo AJ, Lavins BJ et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol 2012; 107: 1702–1712. 22986437
  10. Drossman DA, Chey WD, Johanson JF et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome-results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther 2009; 29: 329–341. 19006537
  11. Spencer AG, Labonte ED, Rosenbaum DP et al. Intestinal inhibition of the Na+/H+ exchanger 3 prevents cardiorenal damage in rats and inhibits Na+ uptake in humans. Sci Transl Med 2014; 6: 227.ra36. 24622516
  12. Johansson S, Rosenbaum DP, Knutsson M et al. A phase 1 study of the safety, tolerability, pharmacodynamics, and pharmacokinetics of tenapanor in healthy Japanese volunteers. Clin Exp Nephrol 2016doi:10.1007/s10157-016-1302-8. PMC5486465 27368672 · DOI
  13. Rome Foundation. Guidelines-Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders. J Gastrointest Liver Dis 2006; 15: 307–312. 17203570
  14. Walter SA, Kjellstrom L, Nyhlin H et al. Assessment of normal bowel habits in the general adult population: the Popcol study. Scand J Gastroenterol 2010; 45: 556–566. 20205503
  15. Schultheis PJ, Clarke LL, Meneton P et al. Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. Nat Genet 1998; 19: 282–285. 9662405
  16. Eutamene H, Bradesi S, Larauche M et al. Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. Neurogastroenterol Motil 2010; 22: 312–e84. 19706070
  17. Block GA, Rosenbaum DP, Leonsson-Zachrisson M et al. Effect of tenapanor on interdialytic weight gain in patients on hemodialysis. Clin J Am Soc Nephrol 2016; 11: 1597–1605. 27340281 PMC5012484
  18. Stefansson BV, Rosenbaum DP, Greasley PJ et al. A phase 2 study on the effect of tenapanor on albuminuria in patients with T2DM and CKD. J Am Soc Nephrol 2015; 26: 239A.25183808
  19. Block GA, Rosenbaum DP, Leonsson-Zachrisson M et al. Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis. J Am Soc Nephrol 2017doi:10.1681/ASN.2016080855. PMC5461797 28159782 · DOI

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Authors
Chey, W. D., Lembo, A. J., & Rosenbaum, D. P.
Affiliations
  • Michigan Medicine (US)
  • Beth Israel Deaconess Medical Center (US)
  • Ardelyx (United States) (US)
Corresponding author
Chey, William D
ORCID
Venue
American Journal of Gastroenterology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-05
Volume
112
Issue
5
Pages
763-774
ISSN
0002-9270 (ISSN-L)
DOI
10.1038/ajg.2017.41
PMC
PMC5418559
OpenAlex
W2593621488
Cited by
102
References
6
Citations by year
2026: 7 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 19 · 2020: 15 · 2019: 9 · 2018: 14 · 2017: 8
FWCI
13.21
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The American Journal of Gastroenterology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Rheumatology › Pelvic floor disorders treatments
Keywords
tenapanor, irritable bowel syndrome with constipation, NHE3 inhibition, Na+/H+ exchanger, gastrointestinal motility, spontaneous bowel movements, abdominal symptoms, diarrhea, drug safety
MeSH terms
Sodium-Hydrogen Exchanger 3, Adult, Aged, Constipation, Defecation, Diarrhea, Double-Blind Method, Female, Gastrointestinal Agents, Humans, Isoquinolines, Male, Middle Aged, Sulfonamides, Abdominal Pain, Treatment Outcome, Sodium-Hydrogen Exchangers, Irritable Bowel Syndrome, Medication Adherence, Symptom Assessment

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