By Sara Freeman
LONDON -- November 24, 2009 -- Adding the investigational agent AZD3355 to proton pump inhibitor (PPI) therapy improves heartburn and regurgitation symptoms in patients with gastro-oesophageal reflux disease (GERD) who repeatedly experience symptoms despite optimal PPI dosing.
Results were reported here November 23 at GASTRO 2009, the joint conference of the United European Gastroenterology Week (UEGW) and the World Congress of Gastroenterology (WCOG).
Data showed that 16% of patients given the novel reflux inhibitor showed a treatment response, whereas only 8% of placebo-treated patients did so (P = .026). A treatment response was defined having not more than one 24-hour period when symptoms of heartburn and/or regurgitation were present, which had to be of mild or lesser intensity and occur during the past 7 days of treatment.
"AZD3355 provides an additional therapeutic option for patients that only partially respond to a PPI," said Guy E. Boeckxstaens, Catholic University of Leuven, Leuven, Belgium, and Academic Medical Center, Amsterdam, the Netherlands. He added that, even though they are treated with PPIs, around 20% to 30% of patients with GERD continue to have reflux symptoms.
AZD3355 decreases the number of transient lower oesophageal sphincter relaxations (TLESRs). TLESRs are thought to be an underlying cause of reflux episodes and thus reducing the number of these could be a new therapeutic target.
The 4-week, double-blind, phase 2 study involved 244 adult patients with GERD who were experiencing reflux symptoms despite 6 weeks of PPI treatment at approved doses.
Efficacy analyses were performed in 114 of those treated with AZD3355 and in 118 of those given placebo. AZD3355 was given at a twice-daily dose of 65 mg, on top of treatment with PPI therapy after an 8- to 12-day run-in period.
Three-quarters of patients (n = 181) experienced daily symptoms of heartburn and/or regurgitation at baseline, 66% were male, and the mean age of patients was 50 years.
Patients given AZD3355 in addition to PPI therapy experienced more symptom-free days than those given placebo, at 36% and 21% for heartburn, respectively, 37% and 23% for regurgitation, and 19% and 10% for either symptom.
Dr. Boeckxstaens reported that the most common side effect seen in the study was diarrhoea, occurring in 11% of AZD3355-treated and 3% of placebo-treated patients. Transient paraesthesia occurred in 8% and 5% of patients, respectively. Nausea occurred in 7% of AZD3355-treated patients, and 3% of those given placebo. Four patients stopped treatment with AZD3355 compared with 2 patients who received placebo because of adverse events.
"This proof-of-concept study shows that add-on treatment with AZD3355 significantly improves GERD symptoms and is well tolerated in patients with GERD with continued symptoms despite PPI therapy," Dr. Boeckxstaens concluded.
"Such findings provide a rationale for further clinical development of this novel reflux inhibitor."
Funding for this study was provided by AstraZeneca.
[Presentation title: Efficacy and Tolerability of the Novel Reflux Inhibitor, AZD3355, as Add-On Treatment in Patients With GERD With Continued Symptoms Despite Proton Pump Inhibitor Therapy. Abstract OP028]
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