title: A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea.
abstract: BACKGROUND
  AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID).
  
  
  METHODS
  Adult patients receiving chemotherapy who had experienced diarrhoea (NCI grade 1-2) during previous cycles of chemotherapy were eligible. In all, 64 patients were randomised to receive AGI004 4 mg then 8 mg per 24 h transdermal patch or placebo for two sequential cycles of chemotherapy. Patients' severity of diarrhoea was physician-assessed using NCI grade of diarrhoea and patient-assessed using information recorded in daily diaries of bowel movements.
  
  
  RESULTS
  Overall AGI004 doubled the odds of a response to treatment on the first day of chemotherapy based on physician assessment of NCI grade of diarrhoea compared with placebo (odds ratio=2.0, 90% confidence interval: 0.9-4.5) and there was a trend to improved response rates for AGI004 for the full treatment cycle although these results were not statistically significant. There was also evidence of significantly improved response rates based on patient assessment of diarrhoea both overall (P=0.05) and at the 8-mg dose level (P=0.02) compared with placebo.
  
  
  CONCLUSIONS
  AGI004 demonstrated effectiveness in reducing chemotherapy-associated diarrhoea, with results suggesting response across multiple measurements of diarrhoea. Treatment was well tolerated with no drug-related adverse events. Further evaluation of this agent in the management of CID is warranted.
authors: NI Cancer Centre, Belfast City Hospital, Belfast BT9 7AB, UK. victoria.coyle@belfasttrust.hscni.net
authors: V M
authors: VM
authors: Coyle
authors: D
authors: D
authors: Lungulescu
authors: C
authors: C
authors: Toganel
authors: A
authors: A
authors: Niculescu
authors: S
authors: S
authors: Pop
authors: T
authors: T
authors: Ciuleanu
authors: C
authors: C
authors: Cebotaru
authors: J
authors: J
authors: Devane
authors: M
authors: M
authors: Martin
authors: R H
authors: RH
authors: Wilson
mesh_terms: D000328:Adult; D000368:Aged; D000930:Antidiarrheals / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage* / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D057968:Transdermal Patch; D016896:Treatment Outcome
chemical_list: D000930:Antidiarrheals; D003692:Delayed-Action Preparations; D010919:Placebos; D008464:Mecamylamine