and the transverse diameter of 4 segments of the colon [ascending (A), transverse (T), descending (D) and sigmoid colon (S)] and the rectum (R) were measured. The stool and/ or gas distribution was evaluated using the following parameters: 1) Constipation index (CI)- summing up the transverse diameter of each of the 5 segments according to the following formula [A+T+D+S+R / 5]; 2) Left/Right ratio (L/R)- calculated from the following formula [(D+S) / (A+T)]. Colon transit time (CTT) was also assessed using radio opaque markers according to the established method by Metcalf, et al. First, patients were treated by either fiber or osmotic laxatives for 2 weeks. When constipation had not improved despite 2 weeks of treatment, stimulant laxatives were prescribed and followed for additional 2 weeks. Results: There was a significantly correlation between CI and CTT (r=0.75, p<0.01) (Fig). CI was significantly higher in CC patients than those with healthy subjects (p<0.05). According to their clinical courses, patients were divided into 3 groups: responder to either fiber or osmotic laxatives (group A), responder to stimulant laxatives (group B), and non- responder (group C). CI was significantly lower in group A compared with both group B and C (p<0.05), and ROC curve analysis gave a cutoff value for CI of 19.7 for prediction of unfavorable outcomes of either fiber or osmotic laxatives (p<0.05), while L/R was signifi- cantly lower in group C compared with group B (p<0.05), and ROC curve analysis gave a cutoff value for L/R of 0.5 for prediction of non-responder of stimulant laxatives (p<0.05). Conclusions: Our data show that the stool and/or gas distribution evaluated by the US becomes an indirect indicator for CTT, and parameters evaluated by the US are associated with responsiveness to medical therapy for CC patients. These findings may assist physicians in predicting the unfavorable outcomes to medical therapies without side effects for this patient population. Correlation between CTT and CI Sa1389 The Safety, Tolerability, and Pharmacokinetics of DA-6886, a Novel Serotonin 5-Hydroxytryptamine 4 Receptor Agonist, in Healthy Subjects Tae-Young Oh, Mun Ju Choi, Byoung-Ok Ahn, Sunghak Choi, Min Jung Lee, Weonbin Im, Yo Han Kim, Hee Youn Choi, Gyun-Sup Bae Background : DA-6886 is a novel prokinetic drug with selective serotonin 5-Hydroxytrypta- mine (5-HT) 4 -receptor agonist that is in the development for the treatment of irritable bowel syndrome with constipation (IBS-C) and functional constipation. Aim : This study aimed to evaluate the safety, tolerability, and pharmacokinetics after single- and multiple- ascending oral dose study and food-effect study. Methods : Three studies were conducted. In double- blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose studies (study 1 and 2), DA-6886 were administered at single doses of 1, 2.5, 5, 10, 20, and 40 mg, with eight subjects in each dose group, including two placebo (study 1), and once-daily dosing for 7 days at 5, 10, and 20 mg with eight subjects in each dose group, including two placebo (study 2). In an open-label, randomized, single dose, 2-period, 2- sequence crossover study in twenty four subjects (study 3), DA-6886 20mg was administered in high-fat fed and fasted states in a randomized sequence, with 7-day wash-out periods. Plasma and/or urine samples were collected after oral administration and the plasma concen- trations of DA-6886 and its metabolite M3 were determined using a validated high-perform- ance liquid chromatography. Pharmacokinetic parameters were obtained by noncompart- mental analysis. Safety and tolerability were assessed based on physical examinations, vital signs, clinical laboratory tests, and electrocardiograms. Results : DA-6886 reached peak plasma concentrations at 0.67-3.00 h, and then declined with a terminal half-life of 11.08- 12.89 h in the single-dose study. The area under the time-concentration curves (AUC) and maximum plasma concentrations (C max ) increased supraproportionally with increasing dose in the single-dose study. During multiple dosing, a steady state was generally considered to be reached after 2 days and systemic exposure to DA-6686 increased 1.88 and 2.18-fold between the doses on day 1 and day 7. In food-effect study, the ratios (90% confidence intervals) of the geometric means compared with the fasting condition for AUC last and C max were 1.39 (1.24, 1.56) and 1.65 (1.46, 1.86) in the high fat-fed condition. DA-6886 was generally well tolerated in these healthy subjects, and no serious adverse event occurred. Conclusions : DA-6886 was well tolerated in healthy volunteers. The AUC and C max of DA-6886 increased supraproportionally with increasing dose upon single and multiple administrations. Food intake increased the absorption and exposure of DA-6886. S-311 AGA Abstracts Sa1390 Efficacy and Safety of Prucalopride in Chronic Constipation: An Integrated Analysis of Six Randomized Controlled Clinical Trials Hubert Piessevaux, Michael Camilleri, Yan Yiannakou, Jan F. Tack, Eamonn M. Quigley, Susana Da Silva Sanchez, Rene Kerstens, Amy Levine Background and aims: Prucalopride, a selective, high-affinity 5-hydroxytryptamine receptor 4 agonist, stimulates gastrointestinal motility and alleviates common symptoms of constipa- tion in adults. The aim of this study was to perform an integrated analysis of the efficacy and safety of prucalopride 2 mg daily in men and women using data from large randomized controlled clinical trials. Methods: Data were combined from six phase 3 and phase 4 multicenter, double-blind, randomized, placebo-controlled, parallel-group trials conducted internationally. Similarities in study design and endpoints of the trials permitted an integrated analysis of the data. The primary efficacy endpoint was the percentage of patients with a mean frequency of ≥ 3 spontaneous complete bowel movements (SCBMs) per week over weeks 1-12 of treatment. Several secondary efficacy endpoints were assessed (at baseline and at the final on-treatment assessment) through patient diaries, and the validated Patient Assessment of Constipation - Symptoms (PAC-SYM) and Patient Assessment of Constipation - Quality of Life (PAC-QOL) questionnaires. Results: Overall, 2484 patients were included in the integrated efficacy analysis and 2552 were included in the integrated safety analysis. Most patients were female (76.0%) and Caucasian (79.0%), and the mean (standard deviation) age overall was 47.5 (15.31) years. The mean duration of constipation was 17.3 (15.04) years and over 60% of patients had had chronic constipation for ≥ 10 years. Consistent with the results found in the individual trials, significantly more patients achieved a mean of ≥ 3 SCBMs per week over weeks 1-12 of treatment in the prucalopride group (27.8%) than in the placebo group (13.2%, p < 0.001); the overall odds ratio was 2.68 (95% confidence interval: 2.16-3.33; Figure). When men and women were considered separately, the primary endpoint was significantly more frequently achieved in the prucalopride treat- ment group than in the placebo group (31.6% vs 16.7% and 26.6% vs 12.2%, respectively, p < 0.001 for both subgroups). At the final on-treatment assessment, the proportion of patients with a clinically meaningful improvement of ≥ 1 point in the PAC-SYM and PAC- QOL total scores from baseline was 9.4% and 14.8% greater, respectively, in the prucalopride group than in the placebo group. Prucalopride had a good safety and tolerability profile. The most common adverse events were gastrointestinal disorders (nausea, diarrhea and abdominal pain) and headache, mainly occurring at the start of treatment. No cardiovascular safety signals were identified. The safety profile of prucalopride was similar in men and women. Conclusion: This integrated analysis demonstrates the consistent efficacy and safety profile of prucalopride for chronic constipation over 12 weeks of treatment in both men and women. Figure. Forest plot comparing prucalopride with placebo for the primary efficacy endpoint for each of the phase 3 and 4 clinical trials and for the integrated (overall) patient population. Sa1391 Shy Bowel Disorder May Be an Under-Recognized Component of Functional Bowel Disease Shreya Raja, Sonali Palchaudhuri, Siddharth Patel, Francis C. Okeke, John O. Clarke, Monica Nandwani, Sameer Dhalla, Pankaj J. Pasricha, Ellen M. Stein Background: Shy Bladder is a voiding disorder characterized by anxiety during urination in public locations. Patients report similar distress passing bowel movements in public restrooms or with travel. We define Shy Bowel disorder (SBD) as a syndrome of shyness at the time of defecation limiting bowel patterns. We adapted Shy Bladder questionnaires to develop a scale of symptoms of SBD. We believe SBD is an under-recognized factor in functional bowel disease correlated with defecatory distress. Patients with chronic constipa- tion often suffer from co-morbid psychiatric conditions such as anxiety, depression and somatization. Aims: 1) To quantify SBD using a novel scale, 2) To describe high resolution anorectal manometry (HRAM) findings in patients with constipation and SBD, 3) To correlate psychometric testing scores with SBD. Methods: We conducted a prospective study on adults at a single academic center undergoing HRAM for constipation and asymptomatic controls at colonoscopy. Study participants completed the Patient Health Questionnaires (PHQ) for depression (PHQ-9), somatization (PHQ-15) and generalized anxiety disorder (GAD-7) as well as a novel 24-item questionnaire with Likert style responses (graded 0-4) called the "Shy Bowel Scale" (SBS). Parties interpreting HRAM were blinded to the results of the questionnaires. Results: 21 patients with chronic constipation (mean age 48 years, 17 female) and 14 controls (mean age 57 years, 6 female) completed the PHQ-9, PHQ-15, GAD-7, and SBS. Positive SBS was defined by a score ≥ 24 (range 0-96), and positive scores indicated that the patient felt symptoms associated with shy bowels such as distress with defecation in a public restroom at least occasionally. Mean scores are reported in Table 1A. AGA Abstracts