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sin the other groups. Occurrence of serious AEs across treatment groups was similar (Table2). AEs leading to discontinuation were more common with naloxegol 25 mg/d, with themost frequently reported AEs being gastrointestinal (GI)-related. There were no notableimbalances in major cardiovascular events across treatment groups. Conclusion: In patientswith OIC, naloxegol treatment increased the frequency of SBMs and resulted in significantlymore OIC responders vs placebo. This effect was maintained over the 12-week treatmentperiod. There was no reversal or reduction of opioid-mediated analgesia as reflected by dailypain scores and opioid dose. Naloxegol was generally well tolerated and safe with the mostcommonly reported AEs being GI-related.Table 1. Primary end point (intention-to-treat [ITT] population)

*Statistically significant under the multiple testing procedure. Analysis via Cochran Mantel-Haenszel test, stratified by baseline laxative response. 11 Patients in KODIAC-04 and -05,found to have been randomized and participating at different centers within the programin parallel are excluded from the ITT and safety analysis sets.Table 2. Safety

AE= adverse event.

901

Effect of the H1-Receptor Antagonist Ebastin on Visceral Perception andClinical Symptoms in IBSSander van Wanrooij, Mira M. Wouters, Lukas Van Oudenhove, Severine Vermeire, PaulJ. Rutgeerts, Guy E. Boeckxstaens

Introduction: Previously we reported that the non-specific mast cell stabilizer and histamine1 receptor (H1R) blocker ketotifen improves visceral hypersensitivity and IBS symptoms.As no reduction in release of mast cell mediators was observed, we hypothesized that H1Rblockade was underlying the beneficial effect of ketotifen. To evaluate our hypothesis, weperformed a double blind randomized controlled trial evaluating the effects of the H1R-antagonist ebastin in IBS patients. Methods: IBS patients with positive Rome III criteria wererandomized to ebastin or placebo treatment during 12 weeks, and were stratified by visceralsensitivity (normo- vs hypersensitive). Sensitivity to rectal distensions was assessed beforeand after treatment. IBS symptoms and health related quality of life were scored before,during and after treatment using the following questionnaires: SGA of relief and abdominalpain, GSRS and IBS-QOL. Primary endpoint was a reduction in VAS score during +21mmHgdistensions of at least 15 points. Secondary endpoints were global symptom relief, abdominalsymptoms, bowel habits and quality of life. Evolution of symptom scores over time ineach treatment group was evaluated using linear mixed models. Results: 55 IBS patients(62%female, age 35±12) were randomly assigned to ebastin (N=28) or placebo (N= 27).VH to rectal distension was present in 45% of patients. Symptom scores evoked by rectaldistention (+3, +9 and +21 mmHg above MDP) were not significantly influenced by ebastin.Over the 12 weeks there was a significant reduction of abdominal pain under ebastin (linearslope time effect= -1.35, p,0.0001), but not during placebo (slope -0.29, p=0.4). Thisdifference in slope between ebastine and placebo was significant (p=0.03), (figure 1A). Atthe end of the 12 weeks treatment, significantly more patients treated with ebastin had atleast considerable relief of symptoms (46% vs 12%, p=0.01, χ2-test, figure 1B), and reportedlower abdominal pain VAS scores (ebastin 38±5, placebo 62±4, Mann-Whittney p=0.001)compared to the placebo group.Other abdominal symptoms, scored using the GSRS question-naire, were not altered during ebastin treatment. QoL was significantly improved on allIBSQOL subscales in the ebastin group compared to baseline and placebo. Finally, nodifference in response to ebastin was observed between the hypersensitive and normosensitivesubgroups. Discussion: Although we failed to show a significant effect on visceral perceptionassessed by rectal distension, ebastin resulted in a significant improvement in global symptomrelief, abdominal pain, and QoL compared to placebo. These data indicate a poor (or evenlack of) relationship between barostat findings and clinical response, but most importantlydemonstrate that H1R blockade may represent an effective treatment for IBS. Trial registrationnumber: NCT01144832

S-160AGA Abstracts

902

Randomized Placebo-Controlled Trial of Glutamine for the Treatment ofDiarrhea-Predominant IBSSapreet Basra, G. Nicholas Verne, QiQi Zhou

Background: Abdominal pain, diarrhea, and urgency are common gastrointestinal symptomsin which the pathophysiology may be related to intestinal hyperpermeability. We havepreviously shown that D-IBS patients have decreased intestinal glutamine synthetase levels(Zhou et. al., Gut, 2010). Despite the clinical usefulness of glutamine, there is no study todate that has evaluated if glutamine supplementation improves gastrointestinal symptomsand restores intestinal permeability in IBS patients. Aim: To determine whether oral glutaminesupplementation can: (1) alleviate symptoms of D-IBS, including abdominal pain, diarrhea,bloating; (2) reverse intestinal hyerpermeability; (3) restore colonic tight junction proteinintegrity such as Claudin-1. Methods: A total of 61 patients with D-IBS were randomizedto receive either oral glutamine, 10 grams 3 times daily or placebo (whey protein) for 8weeks. All patients completed the IBS Symptom Severity Scale (IBSS); a lactulose/mannitolintestinal permeability test, and intestinal biopsies (rPCR for Claudin-1 expression) bothbefore and following the conclusion of the study. Results: Abdominal pain, bloating, anddiarrhea were all significantly improved (p,0.01) in D-IBS patients in the glutamine armcompared to placebo. Intestinal permeability, as measured by the lactulose/mannitol ratio,was restored in IBS patients following glutamine compared to placebo (p ,0.05). There wasa positive correlation between the improvement in IBS symptoms (R=0.7) and colonicClaudin-1 expression (R=0.8) following therapy with oral glutamine supplementation com-pared to placebo (p,0.01). Conclusions: Oral glutamine supplentation improves gastrointes-tinal symptoms and restores normal intestinal permeability in D-IBS patients. The improve-ment in symptoms and intestinal permeability correlated with Claudin-1 expression. Gluta-mine may be a useful therapeutic agent to treat D-IBS patients who have intestinalhyperpermeability. This work was supported by NCCAM (AT005291).

903

TZP-102-Cl-G003 Phase 2B Study Results: Oral TZP-102 Once Daily for 12Weeks in Patients With Diabetic GastroparesisRichard W. McCallum, Elsa Mondou, Joe Quinn, Connie Cosentino, Franck Rousseau

For the TZP-102-CL-G003 Study Team Introduction: TZP-102, a small macrocyclic molecule,is a potent, oral, selective agonist at the heterologously-expressed human ghrelin (GHsecretagogue subtype 1a) receptor. Aim: To evaluate the effect of TZP-102 once daily (QD)for 12 weeks on diabetic gastroparesis symptoms. Methods: Patients with type 1 or 2 diabetesmellitus, with delayed gastric half-emptying time (T1/2) .82 minutes (ABDiagnostics breathtest), and symptoms of gastroparesis for at least 3 months prior to screen were randomized1:1:1 to receive double-blind placebo, 10 mg, or 20 mg TZP-102 QD for 12 weeks. Theprimary outcome measure was the Daily Diary of Gastroparesis Symptoms Questionnaire(GSDD). The GSDD captured the worst severity of nausea, early satiety, bloating, and upperabdominal pain in a 24-hour period on a 6-point scale (0=none; 5=very severe), and wascompleted each day by the patient using an electronic Patient Recorded Outcome (ePRO)device. The GSDD Composite score was defined as the mean of 4 individual symptom