Inhibition of Gastric Acid is the Key to Satisfactory Relief of Symptoms With Esomeprazole in NUD Patients

Enrolled patients will undergo 24h gastric pH monitoring and subsequently (if gastric pH
drops below pH 4 during 24h monitoring) will be randomized to receive placebo (40 mg QD) or
esomeprazole (40 mg QD) for 16 weeks of therapy. 24h gastric pH monitoring will be repeated
2nd and 3rd time in all participating patients at the end of 4th and 8th weeks of therapy.
Additionally, in all participants NUD symptoms will be re-assessed at the end of 4th, 8th,
12th and 16th weeks of therapy.

Inclusion criteria:

A. Males and females of age 18-55. B. A diagnosis of epigastric pain/discomfort (located in
the upper abdomen) rated by the patient as moderate to severe in intensity (on a four-point
categorical scale), which has been present at least 3 times per week for 12 weeks,
unrelated to exercise.

C. Patients may have other symptoms of NUD including heartburn, regurgitation, bloating
(abdominal distension), early satiety (feeling of fullness), belching (burping), or nausea;
however, the dominant symptom must be epigastric pain/discomfort.

D. Capable of and willing to give informed consent and comply with all study requirements.

Exclusion criteria:

A. H. pylori positive serology. B. Regular use of NSAIDs or more than 100 mg of aspirin. C.
Patients requiring chronic treatment with any medication inducing GI symptoms (e.g.,
certain antibiotics, codeine, etc.).

D. History or presence of endoscopic/radiological evidence of esophagitis. E. History or
presence of chronic gastric or duodenal ulcer. F. History or presence of duodenal erosions.
G. History or previous upper GI surgery. H. Presence of concomitant symptoms of irritable
bowel syndrome (IBS) as assessed by three or more of the Manning or Rome criteria.

I. History or presence of other known organic disease that might explain the dyspepsia
symptoms (e.g., symptomatic gallstones).

J. Pregnancy or lactation. K. Inadequate contraception. L. Regular consumption of greater
than 2 fluid ounces of beverage alcohol (corresponding to 2 cocktails or 40 fluid ounces of
beer or 16 fluid ounces of wine) per day.

M. History of substance abuse. N. Unwillingness or expected inability to tolerate absence
of antisecretory medications (antacids, H2 receptor antagonists or PPIs or other GI
pharmacotherapy for a period of time of study protocol (16 weeks maximum).