title: Tenapanor Treatment of Patients With Constipation-Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo-Controlled Efficacy and Safety Trial.
abstract: 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).
  
  
  
  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).
  
  
  
  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%).
  
  
  
  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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Chey
authors.affiliation: Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Lembo
authors.affiliation: Ardelyx, Inc., Fremont, California, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Rosenbaum
mesh_terms: D015746:Abdominal Pain / Q000209:etiology; D000328:Adult; D000368:Aged; D003248:Constipation / Q000150:complications / Q000188:drug therapy*; D003672:Defecation / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D063189:Symptom Assessment; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D007546:Isoquinolines; C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D013449:Sulfonamides; C000599417:tenapanor