Functional dyspepsia - itopride
Dyspepsia that persists or recurs in patients with normal stomach acid levels and no clear physical cause is termed functional dyspepsia. It is not easy to treat, and there are currently no licensed medicines available. Axcan is investigating itopride hydrochloride, licensed from Abbott Laboratories. It is an oral gastroprokinetic drug with antiemetic properties, aimed at the treatment of gastrointestinal symptoms caused by reduced gastrointestinal motility.
Patients with endoscopically confirmed non-ulcer dyspepsia or chronic gastritis were given 50mg itopride hydrochloride three times a day for two weeks in an open label non-comparative study.1 After two weeks, nearly three-quarters of the subjects had moderate to complete relief of symptoms, 17% slight improvement, and the remaining 10% no improvement. It was well tolerated, and no significant side-effects were observed.
In a double blind placebo-controlled Phase II dose-response trial, 554 subjects with functional dyspepsia were given 50, 100 or 200mg itopride or placebo three times a day. Of those given the active, respectively for the ascending doses, 61, 63 and 71% of the subjects remained symptom free, compared with 47% of those given placebo. After treatment for eight weeks, itopride was significantly better in its control of the symptoms than placebo.
Prior to commencing Phase III studies, the company carried out a trial to investigate the drug's potential for cardiotoxicity. A total of 162 healthy volunteers were given a 100mg or supratherapeutic dose of 400mg itopride three times a day, or the antibiotic moxifloxacin, which has known cardiac effects, or placebo. Itopride was shown to have no clinically significant cardiotoxic effects.
It has also been investigated as a potential treatment for gastro-oesophageal reflux disease.2 In an open label clinical trial, 26 patients were given 150 or 300mg of itopride three times a day for 30 days. Both doses reduced total symptom scores, with better reductions being seen in those given the higher dose, and no serious adverse events were seen.