A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia.
Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and (13)C breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation (P = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating (P = 0.001) and overall symptom score (P = 0.022), and at week 3 for bloating (P = 0.008) and heartburn (P = 0.041). 100 mg was also better than placebo for QOL (physical function) (P = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated.
Tack
J
J
Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium. jan.tack@med.kuleuven.be
Masclee
A
A
Heading
R
R
Berstad
A
A
Piessevaux
H
H
Popiela
T
T
Vandenberghe
A
A
Kato
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D001944:Breath Tests; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004415:Dyspepsia / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010919:Placebos; D011788:Quality of Life; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
D001549:Benzamides; D005765:Gastrointestinal Agents; D010919:Placebos; D013844:Thiazoles; C410959:Z 338