Nighttime Heartburn Research Articles

The relationship between complaints of night-time heartburn and sleep-related gastroesophageal reflux

This study investigated whether the complaint of night-time heartburn (NHB) as opposed to daytime heartburn (DHB) is a reliable reflection of actual sleep-related reflux events. Three groups of individuals were studied: individuals with complaints of NHB at least twice per week (n = 24), individuals with complaints of DHB (n = 23), and normal participants without any complaints of regular heartburn during the day or night (n = 25). All three groups were studied on one occasion with combined pH monitoring and polysomnography, and subjective questionnaires about sleep disturbance and sleep quality were given to all participants. The NHB group had significantly more sleep-related reflux events compared with both DHB and control groups (P < 0.01). DHB subjects had significantly (P < 0.05) more sleep-related reflux events than normal controls. Total acid contact time (ACT) was significantly (P < 0.05) elevated in the NHB group compared with both the DHB and control group. Sleep-related ACT was also significantly (P < 0.05) elevated in the NHB group compared with the other two groups, while upright (daytime) ACT was not significantly different. The NHB group was significantly (P < 0.05) worse regarding measures of both objective and subjective sleep quality. Subjects with exclusively DHB do have sleep-related reflux that is greater than normal controls. Subjects with NHB have significantly more sleep-related reflux, and both objective and subjective sleep abnormalities compared with normal controls. Complaints of NHB reflect sleep-related reflux events and may be indicative of a more clinically significant condition.

Night-Time Symptoms and Their Impact on Sleep in Patients with Gastroesophageal Reflux Disease Who Have a Partial Response to Proton Pump Inhibitors: A Qualitative Patient Interview Study

Limited data exists about night-time symptoms that are generated directly from patients with gastroesophageal reflux disease (GERD) who have a partial response to proton pump inhibitor (PPI) therapy. This information is needed to select an appropriate instrument in studies in this patient population. The objective of this qualitative interview study was to gain understanding of the night-time symptoms of patients with GERD who had a partial response to PPIs. The specific aims were (i) to evaluate whether GERD symptoms experienced during the night differ from those occurring during the day; and (ii) to understand the impact of night-time symptoms on sleep and next-day functioning. Four US sites participated in this study of patients with GERD who, despite PPI therapy for at least 4 weeks, still experienced both daytime and night-time heartburn and/or regurgitation. Non-responders to PPIs were excluded. Patient statements were coded and grouped by concept. Twenty-nine patients were enrolled. The predominant and most troublesome symptoms during both the day and night were heartburn and regurgitation. At night-time only, expressions describing regurgitation were more frequent than those describing heartburn (62 vs. 26 %). During the daytime only, expressions describing regurgitation and heartburn occurred with similar frequency (21 vs. 27 %). Patients experienced greater severity of heartburn and regurgitation at night than during the day, and the difference was more pronounced for regurgitation. Patients focused on symptom frequency during the day but on symptom severity at night. Of expressions about the impact of night-time GERD symptoms, 46 % described impact on sleep and 41 % described compensatory behaviors when woken up by symptoms. Next-day impacts of night-time symptoms predominantly included changes in diet (53 %). Partial responders to PPI therapy experience similar GERD symptoms at night and during the day. However, regurgitation is more predominant at night than during the day, and at night patients focus more on symptom severity than symptom frequency.

The effect of baclofen on nocturnal gastroesophageal reflux and measures of sleep quality: a randomized, cross‐over trial

Baclofen, a GABA(b) agonist, has been shown to reduce episodes of gastroesophageal reflux (GER). To determine if baclofen would significantly reduce reflux during sleep, and also improve objective and subjective measures of sleep. Twenty-one individuals with complaints of nighttime heartburn at least twice a week and a Carlsson GERD score of at least 5 were studied. Patients underwent polysomnography (PSG) and simultaneous esophageal pH monitoring on two occasions separated by approximately 1 week in a cross-over design. The night of each polysomnographic study, patients consumed a refluxogenic meal. Baclofen (40 mg) or placebo was given in random order 90 min prior to the start of the PSG. Baclofen significantly reduced the number of reflux events compared with placebo. Upright and recumbent acid contact times were both reduced by baclofen vs placebo, but the differences were not significant. Regarding sleep outcomes, several variables were significantly improved by baclofen. Total sleep time and sleep efficiency increased, and wake after sleep onset decreased in the baclofen condition compared with placebo. Proportion of Stage 1 sleep was also significantly decreased on baclofen. In addition to reducing the number of reflux events during sleep, baclofen significantly improved several measures of sleep in patients with documented GER and sleep disturbances. Baclofen could therefore be considered as a useful adjunct therapy to proton pump inhibitors (PPIs) in patients with nighttime heartburn and sleep disturbance who continue to have heartburn and/or sleep complaints despite PPI therapy.

Nocturnal reflux and sleep disturbances: An overlooked link in the past

Gastro-oesophageal reflux disease (GORD) is highly prevalent n western countries. The main clinical manifestations are repreented by heartburn and regurgitation and they are commonly used or the diagnosis of GORD, although their accuracy is far from optial [1]. The above symptoms can occur during the daytime and lso throughout the nocturnal period. In the past, the progressively idespread use of 24-h oesophageal pH-metry showed that the ajority of reflux events belong to the post-prandial periods, whilst hey are much less frequent during the night time [2]. This temporal istribution of abnormal reflux episodes provided the rationale to xplain, at least in part, the benefit of proton pump inhibitors (PPIs) n patients with GORD. In fact, these drugs are more effective durng the daytime, when proton pumps are activated by fractionated eals, than through the night time, when their main pharmacoogical target does not work because of sleep [3]. Despite the above ndings, in the last decade we have witnessed a mounting evidence f the role of night time GORD in provoking a decreased quality of ife, a variety of sleep disorders and diminished work performances 4]. Several epidemiological surveys have confirmed that nocturnal eflux symptoms, in particular heartburn and regurgitation, can be eported by 2 out of 3 patients with GORD [5] and the relationship etween GORD and sleep disorders has been recently established y many studies which have clearly demonstrated that 47–57% of he GORD patients and approximately 25% of the US adult genral population report having heartburn that awakens them from leep during the night [6,7]. Of the GORD patients, 63% report that hey are unable to sleep well, 42% are unable to sleep during a ull night, 39% have to take naps during the day and 34% have to leep in a seated position because of night time heartburn [7]. It as also been shown that sleep deprivation per se can adversely nfluence GORD, in that the inability to have a complete rest during he night is a potential mechanism for increasing the perception of ymptoms in patients with GORD [8]. Another important issue is he still poorly understood role of nocturnal reflux in determining xtra-oesophageal and particularly respiratory symptoms because f the well-known longer-lasting duration and the slower clearing f supine refluxes compared with the daytime ones [9]. Finally, the se of impedance-pH monitoring has shown that nocturnal weakly

The Pattern of Gastroesophageal Reflux in Patients With and Without Nighttime Heartburn

The Pattern of Gastroesophageal Reflux in Patients With and Without Nighttime Heartburn

Distribution of Reflux Events and Acid Contact Time in Individuals With Nighttime Heartburn

Distribution of Reflux Events and Acid Contact Time in Individuals With Nighttime Heartburn

Prevalence of and impact of pantoprazole on nocturnal heartburn and associated sleep complaints in patients with erosive esophagitis

Studies in the United States have revealed that gastroesophageal reflux disease (GERD) patients often suffer from nocturnal symptoms, sleep disturbance, and impaired quality of life. In a large subset of patients, these symptoms persist in spite of acid suppressive therapy. The aim of the present study was to assess the prevalence of heartburn and associated sleep complaints and the response to standard medical therapy with pantoprazole in primary and secondary care esophagitis patients in Belgium. Questionnaires were provided to consecutive patients presenting to primary and secondary care physicians with esophagitis. The questionnaire evaluated the presence of typical reflux symptoms, alarm symptoms, risk factors, and sleep quality impairment as a result of reflux episodes. Results are shown as mean ± standard deviation and compared by Student's t-test or chi-square test. A total of 4061 primary and 5261 secondary care patients (50% female, mean age 53 ± 0.2 years, body mass index of 25.7 ± 0.1 kg/m(2) ) were recruited. Eighty-four percent of patients reported sleep disturbance attributable to nighttime reflux, including typical nighttime supine reflux symptoms (72%), difficulties to fall asleep (39%), waking up during the night (45%), morning fatigue (35%), and reflux symptoms when waking up in the morning (47%). Mild, moderate, or severe nighttime heartburn were reported by, respectively, 30, 35, and 12%, and these numbers were 26, 28, and 6% for nighttime regurgitation. Alcohol (19%), smoking (22%), higher esophagitis grades (grades 2, 3, and 4 in, respectively, 31, 7, and, 7%), alarm symptoms (27%), and more severe heartburn and regurgitation during daytime were all significantly associated with all dimensions of sleep disturbance (P < 0.0001). Obesity was only related to symptoms in supine position and when waking up (P < 0.0001). After 1.4 ± 0.0 months of treatment with pantoprazole, any sleep disturbance had improved in more than 75% of patients, with resolution of nighttime heartburn and regurgitation in, respectively, 75 and 83%. The majority of patients presenting with reflux symptoms and esophagitis in primary or secondary care experience nighttime heartburn and regurgitation, and sleep disturbance by nighttime symptoms is present in 84%. Smoking, alcohol use, higher grades of esophagitis, more severe typical reflux symptoms during daytime, and the presence of alarm symptoms are risk factors for GERD-related sleep disturbance. On standard therapy with pantoprazole, nighttime symptoms improved in more than 75%. These observations support a direct relationship between GERD and sleep disturbance.

Baclofen Decreases Reflux and Improves Sleep Quality In Individuals With Nighttime Heartburn

Baclofen Decreases Reflux and Improves Sleep Quality In Individuals With Nighttime Heartburn

Clinical trial: esomeprazole for moderate‐to‐severe nighttime heartburn and gastro‐oesophageal reflux disease‐related sleep disturbances

Nighttime heartburn, common among patients with gastro-oesophageal reflux disease (GERD), is associated with substantial clinical effects. GERD-related sleep disturbances are underappreciated and undertreated. To evaluate the efficacy of esomeprazole on GERD-related nighttime heartburn and associated sleep disturbances. In this multicentre, randomized, double-blind, placebo-controlled study, patients with moderate-to-severe nighttime heartburn and GERD-related sleep disturbances (endoscopies not required) received esomeprazole 20 mg or placebo each morning for 4 weeks. Heartburn symptoms and GERD-related sleep disturbances were evaluated using the validated Pittsburgh Sleep Quality Index and validated Work Productivity and Activity Impairment Questionnaire. The analysis included 262 patients (esomeprazole, n = 137; placebo, n = 125). Significantly more patients receiving esomeprazole achieved nighttime heartburn relief (primary end point) than those receiving placebo (34.3% vs. 10.4%; P < 0.0001). Secondary end points such as relief of GERD-related sleep disturbances (P = 0.006), days without GERD-related sleep disturbances (P = 0.0003) and complete resolution of sleep disturbances (P < 0.0001) favoured esomeprazole over placebo. Sleep quality, work productivity and regular daily activities also improved significantly with esomeprazole vs. placebo. Esomeprazole 20 mg is effective for patients with moderate-to-severe nighttime heartburn and GERD-related sleep disturbances, improving heartburn symptoms, sleep quality, work productivity and functionality.

W1099 Vecam™: Superior Control of Nighttime Acid Secretion, Towards a Novel Treatment for Nighttime Heartburn

W1099 Vecam™: Superior Control of Nighttime Acid Secretion, Towards a Novel Treatment for Nighttime Heartburn

Onset of relief of symptoms of gastroesophageal reflux disease: Post hoc analysis of two previously published studies comparing pantoprazole 20 mg once daily with nizatidine or ranitidine 150 mg twice daily

Background: Systematic assessments of the onset of symptom relief in the treatment of gastroesophageal reflux disease (GERD) are lacking. Objective: This work evaluated the time interval until complete symptom relief from heartburn (including both daytime and nighttime heartburn) and acid regurgitation in patients with GERD or endoscopy-negative GERD (NERD) during the first 7 days of treatment with pantoprazole, nizatidine, or ranitidine. Methods: This was a post hoc reanalysis of data from 2 previously published, multicenter, randomized, doubleblind, active-controlled, parallel-group studies. Male and female patients aged ≥18 years with endoscopically proven GERD or NERD (Hetzel-Dent grade ≥ [trial 1] or Savary-Miller grade 0 or 1 [trial 2]) were enrolled. Patients were required to have had reflux symptoms for the previous ≥3 months, with ≥1 symptom (ie, daytime heartburn, nighttime heartburn, or acid regurgitation) for ≥4 of the past 7 days in trial 1 or ≥1 symptom (ie, heartburn, acid eructation, or painful swallowing) of at least moderate intensity for the past 3 days in trial 2. The treatments were pantoprazole 20 mg once daily in both trials, nizatidine 150 mg BID in trial 1, or ranitidine 150 mg BID in trial 2. Presence and severity of symptoms were recorded on daily diary cards using a 4-point Likert-type scale. Results: In total, 114 patients from trial 1 and 307 patients from trial 2 were evaluable for heartburn, and 58 patients from trial l and 271 patients from trial 2 were evaluable for acid regurgitation. In both studies, there were no significant differences in baseline characteristics between pantoprazole recipients and nizatidine or ranitidine recipients, with the exception of more men than women in trial 1 compared with trial 2 ( P < 0.001). On day 2 of trial 1, 23 (39.0%) and 8 (14.5%) of pantoprazole and nizatidine recipients, respectively, experienced complete relief from heartburn ( P < 0.01). The differences between groups remained statistically significant through day 7, when 28 (47.5%) and 8 (14.5 %) of pantoprazole and nizatidine recipients had no heartburn ( P < 0.001). There were no differences in control of acid regurgitation over 7 days with pantoprazole compared with nizatidine or ranitidine, except at days 2 and 4 of trial 1, when significantly more patients receiving pantoprazole experienced relief from acid regurgitation than those receiving nizatidine (day 2: 60.6% [n = 20] vs 20.0% [n = 5], P < 0.01; day 4: 48.5% [n =16] vs 24.0% [n = 6], P < 0.05). Conclusion: In this post hoc reanalysis of data from 2 previously published clinical trials, use of pantoprazole 20 mg once daily was associated with effective early relief from heartburn and acid regurgitation among these patients with GERD and NERD; relief occurred as fast as and, in some cases, even faster than that seen with nizatidine or ranitidine.

Sleep Dysfunction in Japanese Patients with Gastroesophageal Reflux Disease: Prevalence, Risk Factors, and Efficacy of Rabeprazole

Background and Aim: Several studies performed in Western countries demonstrate the association between sleep dysfunction and gastroesophageal reflux disease (GERD), especially when nighttime heartburn is present. The purpose of this study was to examine the prevalence and risk factors of sleep dysfunction, and the effect of rabeprazole on reflux symptoms and sleep dysfunction in Japanese GERD patients. Methods: A total of 134 GERD patients, including 82 patients with non-erosive reflux disease (NERD), were enrolled. Patients received rabeprazole 10 mg daily for 8 weeks. Patients were asked to complete both a frequency scale for symptoms of GERD (FSSG) questionnaire and a Pittsburgh Sleep Quality Index (PSQI) questionnaire at baseline and 8 weeks after treatment. Results: Sleep dysfunction defined as a PSQI score >5.5 was found in 70 (52.2%) of the GERD patients. NERD was significantly associated with sleep dysfunction compared to erosive reflux disease (OR 2.18, 95% CI 1.05–4.53). However, other factors, including nighttime heartburn, were not associated with sleep dysfunction. Rabeprazole treatment significantly decreased both the FSSG and the PSQI score. Conclusion: The prevalence of sleep dysfunction was high among GERD patients. NERD was identified as a risk factor for sleep dysfunction. Use of a proton-pump inhibitor led to an effective decrease in sleep dysfunction. These results suggest a different pathogenesis of sleep dysfunction in Japanese GERD patients compared to GERD patients in Western countries. However, acid plays an important role in sleep dysfunction in all patients with GERD.

Patient Self-Treatment Using Lansoprazole for Frequent Nighttime Heartburn

Practice PearlLansoprazole 15 mg or, 30 mg effectively reduced, frequent nighttime heartburn.

Review article: sleep‐related gastro‐oesophageal reflux as a distinct clinical entity

Many patients with chronic gastro-oesophageal reflux disease (GERD) have frequent nighttime heartburn as well as sleep-related gastro-oesophageal reflux (GOR). Sleep-related GOR has been shown to play an important role in the development of oesophagitis and other complications of GOR. To present a conceptual argument that nighttime heartburn and associated sleep-related GOR should be recognized as a distinct clinical entity deserving special attention with regard to the diagnosis and treatment of GERD. The data presented come from surveys of GERD patients as well as from physiological studies to include studies monitoring oesophageal pH and spontaneous reflux events during polysomnographically (PSG) monitored sleep. Evidence is presented to show that nighttime heartburn is prevalent and its occurrence separates patients from those who have heartburn most exclusively in the daytime. The evidence presented also supports the notion that nighttime heartburn sufferers have a more complicated disease and they have a greater risk of developing oesophagitis and other respiratory complications. The data also show that responses to acid mucosal contact are quite different during sleep compared to responses measured during the waking state. Nighttime heartburn and GOR represent a distinct clinical entity which deserves specific attention in the diagnosis and optimal treatment of GERD.

The Relationship Between the Prevalence of Nighttime Gastroesophageal Reflux Disease and Disease Severity

Nighttime gastrointestinal reflux disease (GERD) prevalence and severity estimates vary substantially across studies. We assessed nighttime GERD (NTG) prevalence and symptom frequency and severity through a web survey of US adults, using the GERD Symptom and Medication Questionnaire (GERD-SMQ), a validated symptom questionnaire. NTG was based on episodes of nighttime heartburn per week and time of occurrence. Symptom severity and impact were assessed and compared for GERD cases with and without NTG. GERD prevalence among respondents (n = 2,603) was 27%. Forty-five percent of symptomatic GERD respondents had NTG. Among respondents with both daytime and nighttime symptoms, 51% reported that nighttime symptoms were more bothersome. NTG respondents reported greater disease severity compared with those without (P < 0.0001). NTG symptoms are very common among those identified with GERD. People with nighttime symptoms have greater disease severity than those with exclusively or primarily daytime symptoms.

Clinical trial: lansoprazole 15 or 30 mg once daily vs. placebo for treatment of frequent nighttime heartburn in self‐treating subjects

Frequent nighttime heartburn is common. Lansoprazole 15 mg is indicated for treatment of heartburn and other gastro-oesophageal reflux disease-related symptoms. To evaluate the efficacy and safety of lansoprazole in self-treating subjects with frequent nocturnal heartburn. A total of 864 subjects with heartburn on >or=2 days/week over the past month were randomized to double-blind treatment with lansoprazole 15 or 30 mg or placebo each morning. Endpoints were percentage of night times without heartburn (primary), percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1. Mean percentage of night times without heartburn was significantly greater with lansoprazole 15 mg (61.3%) or lansoprazole 30 mg (61.7%) vs. placebo (47.8%) over 14 days (P < 0.0001 vs. placebo for both doses). Percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1 were significantly greater with lansoprazole 15 or 30 mg vs. placebo. Both lansoprazole 15 and 30 mg were highly effective and well tolerated in reducing symptoms in subjects with frequent nighttime heartburn. The benefit of therapy on 24-h heartburn and nighttime heartburn on day 1 of treatment was also evident. Lansoprazole 15 mg is a suitable choice for management of frequent nighttime heartburn.

Lansoprazole 15 mg Once Daily for 14 Days Is Effective for Treatment of Frequent Heartburn: Results of 2 Randomized, Placebo-Controlled, Double-Blind Studies

Objective: To investigate the efficacy and safety of a 14-day treatment period with lansoprazole 15 mg for frequent heartburn in patients who are likely to select a nonprescription medication before consulting a prescriber. Methods: Adults with untreated frequent heartburn ≥ 2 days a week over the past month were recruited for 2 identical multicenter, double-blind studies conducted with a 1-week screening and heartburn medication washout, a 1-week placebo run-in, a 2-week placebo-controlled treatment, and a 1-week placebo follow-up. After the washout and placebo run-in, subjects were randomly assigned to receive lansoprazole 15 mg or placebo once daily for 14 days in a double-blind fashion. Antacid tablets were permitted as rescue medication. Endpoints included percentage of 24-hour days without heartburn (primary), percentage of night-times without heartburn, and percentage of subjects without heartburn during day 1 of treatment (secondary endpoints). Data were collected daily via an interactive voice response system. Results: In studies 1 and 2, 282 and 288 subjects, respectively, were randomly assigned to lansoprazole, and 282 in each study received placebo. The mean percentage of days without heartburn was greater among lansoprazole recipients compared with placebo recipients (P < 0.0001). Significantly more subjects treated with lansoprazole also reported no night-time heartburn and no heartburn during day 1 of the 14-day treatment. Adverse events were infrequent and were similar for lansoprazole and placebo groups. Conclusion: During the 14-day treatment period in a population with frequent heartburn who were likely to select a medication without consulting a prescriber, lansoprazole 15 mg once daily showed rapid and sustained effectiveness throughout a 24-hour period and was well tolerated.

Rabeprazole 20 mg for Erosive Esophagitis-Associated Symptoms in a Large, Community-Based Study: Additional Results

To provide additional efficacy data in patients treated with rabeprazole through week 4, and to validate sustained relief of gastroesophageal reflux disease symptoms through week 8 as well as to further analyze rabeprazole safety in patients with wide-ranging demographic and clinical characteristics. Patients in this study (N = 2,449) demonstrated significant overall improvement versus baseline (P < 0.001). Substantial symptom relief was seen throughout 8 weeks of treatment. By week 4, complete relief of daytime and nighttime heartburn, belching, regurgitation, and dysphagia was observed in 87.5, 90.7, 50.7, 77.6, and 75.1% of patients, respectively. Improvements were seen in rabeprazole-treated patients (<65 or >or=65 years) with a range of baseline symptom severities and across different racial groups. Rabeprazole was well tolerated. In patients with endoscopy-confirmed erosive esophagitis treated with once-daily rabeprazole 20 mg, prompt and continuing improvements were seen in daytime and nighttime heartburn, belching, regurgitation, and dysphagia.

Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non‐erosive reflux disease

The proportion of patients who respond to proton pump inhibitor (PPI) therapy is about 20% lower in those with non-erosive reflux disease (NERD) than in those with erosive oesophagitis. To assess efficacy and safety of dexlansoprazole MR, a PPI using Dual Delayed Release technology, in NERD patients. In this 4-week, double-blind, placebo-controlled study, 947 NERD patients randomly received dexlansoprazole MR 30 mg, 60 mg or placebo once daily (QD). The percentages of 24-h heartburn-free days (primary) and nights without heartburn (secondary) were assessed from patients' daily diaries. Investigators also assessed symptoms. Patients completed validated quality of life and symptom severity questionnaires. Dexlansoprazole MR provided significantly greater median percentages of 24-h heartburn-free days (54.9% and 50.0% for the 30- and 60-mg doses vs. 17.5% for placebo, P < 0.00001) and nights without heartburn (80.8% and 76.9% vs. 51.7%, P < 0.00001 vs. placebo). Dexlansoprazole MR also reduced symptom severity. Quality of life improvements in patients receiving dexlansoprazole MR were consistent with clinical efficacy endpoints. Percentages of patients experiencing treatment-emergent adverse events were similar among groups. Dexlansoprazole MR 30 and 60 mg were superior to placebo in providing 24-h heartburn-free days and nights in NERD patients. Treatment was well tolerated.

M1868 Esomeprazole for the Relief of Nighttime Heartburn in Patients with Gastroesophageal Reflux Disease (GERD)-Related Sleep Disturbances

test and comparison to placebo by Wilcoxon Rank Sum test. Results. In the placebo group reflux episodes increased from D-1 to D6. This effect was reduced in the ADX10059 treatment groups. A significant treatment effect was seen for total acid exposure % (p=0.048) and number of weakly acidic reflux episodes (p = 0.0411). Significant differences from placebo were seen for 125mg b.i.d for various reflux measures. Trends were also seen for the 250mg b.i.d. dose which did not appear more effective than 125mg b.i.d. The 50mg b.i.d dose was not significantly superior to placebo. Twice daily administration of ADX10059 gave satisfactory 24 hour plasma concentrations. All 3 doses were well tolerated. Adverse event frequency was 50 mg : n=3 ; 125 mg : n=8 ; 250 mg : n=9. All were mild or moderate. Themost commonwere insomnia (n=4), constipation (n=2) and flatulence (n=2). Conclusion. Compared to placebo, ADX10059 dose dependently decreased gastro-esophageal reflux events in healthy subjects. The tolerability of the MR formulation is suitable for longer term treatment to evaluate clinical symptom control in GERD patients. Median and 95% CI of changes Day -1 to Day 6 for 5 hour pH-impedance monitoring period