PMID- 18775020
OWN - NLM
STAT- MEDLINE
DCOM- 20081028
LR  - 20151119
IS  - 1572-0241 (Electronic)
IS  - 0002-9270 (Linking)
VI  - 103
IP  - 10
DP  - 2008 Oct
TI  - Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor 
      antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in 
      patients with irritable bowel syndrome.
PG  - 2562-9
LID - 10.1111/j.1572-0241.2008.02115.x [doi]
AB  - OBJECTIVES: 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.
FAU - Drossman, Douglas A
AU  - Drossman DA
AD  - Division of Gastroenterology and Hepatology, University of North Carolina Center 
      for Functional GI and Motility Disorders, Chapel Hill, North Carolina 27599-7080, 
      USA.
FAU - Danilewitz, Mervyn
AU  - Danilewitz M
FAU - Naesdal, Jorgen
AU  - Naesdal J
FAU - Hwang, Clara
AU  - Hwang C
FAU - Adler, John
AU  - Adler J
FAU - Silberg, Debra G
AU  - Silberg DG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080904
PL  - United States
TA  - Am J Gastroenterol
JT  - The American journal of gastroenterology
JID - 0421030
RN  - 0 (Benzopyrans)
RN  - 0 (Serotonin 5-HT1 Receptor Antagonists)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - I18M56OGME (robalzotan)
SB  - IM
MH  - Abdominal Pain/diagnosis/drug therapy/*etiology
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Benzopyrans/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Irritable Bowel Syndrome/complications/*drug therapy/metabolism
MH  - Male
MH  - Middle Aged
MH  - Pain Measurement
MH  - Prospective Studies
MH  - Quality of Life
MH  - Receptor, Serotonin, 5-HT1A/metabolism
MH  - *Serotonin 5-HT1 Receptor Antagonists
MH  - Surveys and Questionnaires
MH  - Treatment Outcome
EDAT- 2008/09/09 09:00
MHDA- 2008/10/29 09:00
CRDT- 2008/09/09 09:00
PHST- 2008/09/09 09:00 [pubmed]
PHST- 2008/10/29 09:00 [medline]
PHST- 2008/09/09 09:00 [entrez]
AID - AJG2115 [pii]
AID - 10.1111/j.1572-0241.2008.02115.x [doi]
PST - ppublish
SO  - Am J Gastroenterol. 2008 Oct;103(10):2562-9. doi: 
      10.1111/j.1572-0241.2008.02115.x. Epub 2008 Sep 4.