Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome.
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.
Drossman
Douglas A
DA
Division of Gastroenterology and Hepatology, University of North Carolina Center for Functional GI and Motility Disorders, Chapel Hill, North Carolina 27599-7080, USA.
Danilewitz
Mervyn
M
Naesdal
Jørgen
J
Hwang
Clara
C
Adler
John
J
Silberg
Debra G
DG
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
D001578:Benzopyrans; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C108607:robalzotan