title: Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome.
abstract: OBJECTIVE
  To investigate the efficacy and safety of the 5-hydroxytrypamine 1A (5-HT(1A)) receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate), termed AZD7371 here, in patients with irritable bowel syndrome (IBS).
  
  
  METHODS
  Patients meeting the Rome II criteria for IBS (N = 402) were randomized to treatment with AZD7371 20 mg or 5 mg or matching placebo tablets twice daily for 12 wk. The patients completed daily and weekly diary assessments, reporting abdominal discomfort or pain and description of bowel movements. They also completed validated symptom and quality-of-life questionnaires.
  
  
  RESULTS
  Neither AZD7371 regimen was significantly more effective than placebo in providing adequate relief from IBS symptoms in at least 2 out of 4 wk per month over the 12 wk of treatment. There was also no significant difference between the treatment groups and placebo in the change in score in the validated symptom and quality-of-life questionnaires. Overall, 22.1% of patients experienced adverse events (AEs) attributed to the study medication: 44 of 133 (33.1%) in the 20 mg AZD7371 group, 27 of 131 (20.6%) in the 5 mg AZD7371 group, and 17 of 134 (12.7%) in the placebo group. Also, 31 of 57 (54%) of AEs leading to discontinuation were central nervous system-related. Hallucinations or hallucination-like AEs were reported by eight patients taking AZD7371, and by none of the patients in the placebo group. After these events led to discontinuation in six patients, the study was prematurely terminated.
  
  
  CONCLUSIONS
  In view of the AE profile and lack of efficacy in IBS, the clinical development of AZD7371 has been stopped.
authors.affiliation: Division of Gastroenterology and Hepatology, University of North Carolina Center for Functional GI and Motility Disorders, Chapel Hill, North Carolina 27599-7080, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Drossman
authors.forename: Mervyn
authors.initials: M
authors.lastname: Danilewitz
authors.forename: Jørgen
authors.initials: J
authors.lastname: Naesdal
authors.forename: Clara
authors.initials: C
authors.lastname: Hwang
authors.forename: John
authors.initials: J
authors.lastname: Adler
authors.forename: Debra G
authors.initials: DG
authors.lastname: Silberg
mesh_terms: D015746:Abdominal Pain / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001578:Benzopyrans / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011446:Prospective Studies; D011788:Quality of Life; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D001578:Benzopyrans; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C108607:robalzotan