A randomized, comparative study of three doses of AZD0865 and esomeprazole for healing of reflux esophagitis.
OBJECTIVE
AZD0865 belongs to a new class of acid-suppressing agents with rapid onset of action and potent acid inhibition. We evaluated its effectiveness for healing reflux esophagitis.


METHODS
One thousand five hundred twenty-one patients with Los Angeles A-D esophagitis and heartburn of moderate or severe intensity for > or = 4 days/week were randomized to AZD0865 25, 50, or 75 mg or esomeprazole 40 mg once daily for 4-8 weeks. The primary end point was esophagitis healing by AZD0865 at 4 weeks. Healing and control of heartburn were also assessed at 2, 4, and 8 weeks for AZD0865 and esomeprazole.


RESULTS
After 4 weeks of treatment, healing rates were similar among AZD0865 doses (76.9%; confidence interval [CI], 72.4%-81.1%); 78.2% (CI, 73.7%-82.3%), and 81.1% (CI, 76.7%-84.9%) for 25, 50, and 75 mg, respectively). The healing rate with esomeprazole at 4 weeks was similar (81.9%; CI, 77.6%-88.7%), and healing rates also were comparable among all treatments at 2 and 8 weeks. There were no significant differences in heartburn control among treatments. AZD0865 and esomeprazole were well-tolerated, although reversible increases in transaminases occurred in a small number of patients receiving AZD0865, especially at the 75-mg dose.


CONCLUSIONS
AZD0865 25, 50, and 75 mg provided similar efficacy to esomeprazole 40 mg in terms of esophagitis healing and heartburn control. These findings suggest that increasing the degree of acid inhibition beyond that already achieved by esomeprazole 40 mg (or AZD0865 25 mg) does not translate into increased clinical efficacy in esophagitis patients.
Kahrilas
Peter J
PJ
Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611-2951, USA. p-kahrilas@northwestern.edu
Dent
John
J
Lauritsen
Karsten
K
Malfertheiner
Peter
P
Denison
Hans
H
Franzén
Stefan
S
Hasselgren
Goran
G
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D064098:Esomeprazole / Q000008:administration & dosage / Q000627:therapeutic use*; D004942:Esophagitis, Peptic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005745:Gastric Acidity Determination; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
C514958:AZD0865; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D064098:Esomeprazole