Withdrawing PPI therapy after healing esophagitis does not worsen symptoms or cause persistent hypergastrinemia: analysis of dexlansoprazole MR clinical trial data.

OBJECTIVES: Withdrawal of proton pump inhibitors (PPIs) may induce symptoms in healthy volunteers, suggesting that discontinuing PPI therapy induces acid-peptic disease. Similar assessments in patients with documented acid-related disorders are lacking. METHODS: We performed a retrospective analysis of data from 287 Helicobacter pylori-negative erosive esophagitis (EE) patients healed after 4 or 8 weeks of therapy with dexlansoprazole modified release (MR) or lansoprazole, and then randomized to placebo in 6-month maintenance trials. We compared serum gastrin levels and 24-h heartburn severity before enrollment in the healing trials (baseline) and after receiving placebo in the 6-month maintenance trials. RESULTS: Mean gastrin values at maintenance months 1 and 3 were essentially unchanged (median changes, 1.0 and -1.0 pg/ml), showing that gastrin normalized within 1 month of discontinuing PPIs and remained flat. Mean heartburn severity at maintenance month 1 was <1 on a 5-point scale (1=mild) and significantly lower than at baseline (median decrease, 0.41 points; P≤0.001). Heartburn severity in patients healed at week 4 or 8 with either PPI was generally similar, suggesting that neither longer exposure nor more potent therapy was associated with rebound. In those with month 2 data, mean heartburn severity at months 1 and 2 was significantly lower than baseline (median decrease, 0.54 and 0.58 points; both P<0.001), indicating an ongoing symptom response for 2 months after PPI withdrawal. CONCLUSIONS: In H. pylori-negative EE patients, there was no indication of recurring heartburn symptom worsening beyond baseline levels within 2 months of discontinuing 4-8 weeks of PPI therapy.

The effect of dexlansoprazole MR on nocturnal heartburn and GERD-related sleep disturbances in patients with symptomatic GERD.

OBJECTIVES: Nocturnal heartburn and related sleep disturbances are common among patients with gastroesophageal reflux disease (GERD). This study evaluated the efficacy of dexlansoprazole MR 30 mg in relieving nocturnal heartburn and GERD-related sleep disturbances, improving work productivity, and decreasing nocturnal symptom severity in patients with symptomatic GERD. METHODS: Patients (N=305) with frequent, moderate-to-very severe nocturnal heartburn and associated sleep disturbances were randomized 1:1 in a double-blind fashion to receive dexlansoprazole MR or placebo once daily for 4 weeks. The primary end point was the percentage of nights without heartburn. Secondary end points were the percentage of patients with relief of nocturnal heartburn and of GERD-related sleep disturbances over the last 7 days of treatment. At baseline and week 4/final visit, patients completed questionnaires that assessed sleep quality, work productivity, and the severity and impact of nocturnal GERD symptoms. RESULTS: Dexlansoprazole MR 30 mg (n=152) was superior to placebo (n=153) in median percentage of nights without heartburn (73.1 vs. 35.7%, respectively; P<0.001). Dexlansoprazole MR was significantly better than placebo in percentage of patients with relief of nocturnal heartburn and GERD-related sleep disturbances (47.5 vs. 19.6%, 69.7 vs. 47.9%, respectively; P<0.001), and led to significantly greater improvements in sleep quality and work productivity and decreased nocturnal symptom severity. Adverse events were similar across treatment groups. CONCLUSIONS: In patients with symptomatic GERD, dexlansoprazole MR 30 mg is significantly more efficacious than placebo in providing relief from nocturnal heartburn, in reducing GERD-related sleep disturbances and the consequent impairments in work productivity, and in improving sleep quality/quality of life.

Comparison of the effects of single and repeated oral doses of lansoprazole and rabeprazole on ambulatory 24-hour intragastric pH in healthy volunteers.

BACKGROUND: As the comparative pharmacokinetics and pharmacodynamics of lansoprazole and rabeprazole have not previously been studied, we set out in this study to compare the pharmacokinetics and pharmacodynamics of single and repeated daily doses of lansoprazole 15 mg and 30 mg with those of rabeprazole 10 mg and 20 mg. METHODS: This was an open-label, randomised, crossover, two-centre study in 72 healthy volunteers. Each subject received each of the four treatments for 5 days, with 2-week washout periods. Continuous 24-hour intragastric pH and pharmacokinetics were studied on days 1 and 5. RESULTS: Mean 24-hour pH and percentage time for pH > 4 were not significantly different between lansoprazole 30 mg and rabeprazole 20 mg. Mean 24-hour pH and percentage time for pH > 4 were significantly greater after lansoprazole 30 mg and rabeprazole 20 mg than after lansoprazole 15 mg and rabeprazole 10 mg, respectively. Lansoprazole resulted in greater acid suppression during hours 0-5 on days 1 and 5, whereas rabeprazole had greater suppression during hours 11-24 on day 5. Time to maximum plasma concentration was significantly shorter for lansoprazole on both days. CONCLUSION: Lansoprazole had a consistently faster onset of action, whereas rabeprazole had a greater effect during the evening hours after 5 days of administration.

Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials.

PURPOSE: The efficacy of proton pump inhibitor therapy for symptom resolution in patients with functional dyspepsia remains controversial. This study was designed to compare the efficacy of lansoprazole with placebo in relieving upper abdominal discomfort in patients with functional dyspepsia. METHODS: We enrolled 921 patients with functional dyspepsia (defined as persistent or recurrent upper abdominal discomfort during the prior 3 months) and moderate upper abdominal discomfort on at least 30% of screening days; none of the patients had predominant symptoms suggestive of gastroesophageal reflux or endoscopic evidence of erosive or ulcerative esophagitis, or gastric or duodenal ulcer or erosion. Patients were assigned randomly to receive lansoprazole 15 mg (n = 305), lansoprazole 30 mg (n = 308), or placebo (n = 308) daily for 8 weeks. Patients recorded the frequency and severity of symptoms in daily diaries. RESULTS: At week 8, significantly (P <0.001) greater mean reductions in the percentage of days with upper abdominal discomfort were reported in patients treated with lansoprazole 15 mg (35%) or 30 mg (34%) compared with those treated with placebo (19%). Similarly, more patients treated with lansoprazole 15 mg (44%) or 30 mg (44%) reported complete symptom resolution (defined as no episodes of upper abdominal discomfort in the 3 days before the study visit) at 8 weeks than did placebo-treated patients (29%, P <0.001). Improvement of upper abdominal discomfort, however, was seen only in patients who had at least some symptoms of heartburn at enrollment. CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30 mg, is significantly better than placebo in reducing symptoms of persistent or recurrent upper abdominal discomfort accompanied by at least some symptoms of heartburn.

Bioavailability of lansoprazole granules administered in juice or soft food compared with the intact capsule formulation.

BACKGROUND: The ability to administer the contents of an encapsulated-dose formulation in liquids or soft foods without compromising drug bioavailability is highly desirable for patients who are unable to swallow or have difficulty swallowing. OBJECTIVE: The purpose of this study was to compare the bioavailability of lansoprazole granules administered in 2 types of juice and a soft food with that of the intact capsule administered with water. METHODS: Healthy adult volunteers were eligible for this single-center, Phase I, single-dose, randomized, open-label, 4-period crossover study. Subjects received the enteric-coated granular contents of a 30-mg lansoprazole capsule in 3 test regimens (in 180 mL of orange juice, 180 mL of tomato juice, or 1 tablespoon of strained pears, each followed by 180 mL of water) and 1 reference regimen (the 30-mg intact capsule with 180 mL of water). The regimens were rotated at > or = 6-day intervals so that each subject received all 4 regimens. Blood samples for pharmacokinetic analyses were obtained during the 12 hours after each regimen. RESULTS: Twenty healthy adult volunteers (10 men, 10 women; mean age, 36 years [range, 19-53 years]) completed this study. Bioavailability of the 3 test regimens was assessed using the two 1-sided tests procedure for mean maximum plasma concentration and area under the plasma concentration-time curve (AUC) from time 0 through the last measurable concentration and AUC from time 0 to infinity. These results were compared with that of the intact capsule. This comparison indicated that the 90% CIs for all 3 test regimens were within the acceptable bioequivalence range of 0.80 to 1.25. Lansoprazole was well tolerated, with most of the adverse events being mild. Headache was the most frequently reported adverse event. CONCLUSION: The results of this study indicate that the bioavailability of lansoprazole granules, when administered in orange juice, tomato juice, or a small amount of strained pears, was similar to that of the intact capsule in these healthy adult volunteers.

Proton pump inhibitors: effective first-line treatment for management of dyspepsia.

The aim of this study was to evaluate the reasons for trial exclusion among dyspeptic patients and estimate the proportion that may have benefited from proton pump inhibitor (PPI) therapy. Stringent inclusion criteria for enrollment in two multicenter functional dyspepsia trials included dyspepsia (predominant persistent/recurrent upper abdominal discomfort [UAD] during the prior 3 months) of at least moderate intensity during > or =30% of days during the prior 2 to 3 weeks. Exclusion criteria were mild/infrequent UAD; heartburn and UAD of equal frequency; predominant heartburn with UAD; endoscopic evidence of erosive esophagitis or Barrett's or gastric and/or duodenal erosions (>5) or ulcers; irritable bowel syndrome (IBS); other gastrointestinal diagnoses; or other "non-categorized" disorders. Of 2,588 screened patients, 1,667 were excluded. Excluded patients by category had mild/infrequent UAD (12.5%, n=324), heartburn and UAD of equal frequency (1.1%, n=29), predominant heartburn with UAD (11.6%, n=300), endoscopic evidence of erosive esophagitis or Barrett's (6.2%, n=160), gastric and/or duodenal erosions (1.4%, n=36), gastric and/or duodenal ulcers (2.0%, n=53), IBS (7%, n=180), "other" gastrointestinal diagnoses (2.8%, n=73), or other "non-categorized" disorders (19.8%, n=512). Fifty-four percent of patients (902/1,667) had symptoms/diagnoses that would be expected to improve with PPI therapy. Individuals with IBS, "other," or "non-categorized" disorders were considered to have symptoms unlikely to respond to PPI treatment. Empiric PPI treatment would be expected to provide symptom relief to the majority of dyspepsia sufferer who present in clinical practice. PPIs represent the best currently available therapy for acid-related disorders and should be considered the first-line management approach in patients with uninvestigated dyspepsia.