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Su2067 Results of Gastric Emptying Tested With Wireless Motility Capsule in Chronic Constipation Patients Before and After Lubiprostone
Su2068
Efficacy of a Polyethylene Glycol Laxative (PEG, Macrogol 4000) Versus Lactulose for the Treatment of Chronic Constipation in Children. Results of a Randomized, Double-Blind Controlled Study Performed in Thailand Suporn Treepongkaruna, Nipat Simakachorn, Paneeya Pienvichit, Axel Magis, Philippe Garnier, Pascal Maisonobe, Hélène Mathiex-Fortunet
Efficacy of Combination Therapy of Probiotics and Mosapride in Patients With IBS Without Diarrhea: Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Trial Chang Hwan Choi, Joong Goo Kwon, Sung-Kook Kim, Seung-Jae Myung, Kyung Sik Park, Chong Il Sohn, Poong-Lyul Rhee, Kwang Jae Lee, Oh Young Lee, Hye-Kyung Jung, Sam Ryong Jee, Yoon Tae Jeen, Myung-Gyu Choi, Suck Chei Choi, Kyuchan Huh, Hyojin Park
Introduction: The study is the first one in Asia comparing a PEG 4000 to another osmotic laxative (lactulose) in children with chronic constipation. Patients and Methods: This randomized, double-blind, lactulose controlled study was conducted in 2 parallel groups in 2 centers in 88 children in Thailand. Male or female (outpatient) children aged between 12 to 36 months were included if they had a chronic constipation (defined as ≥ 3 months of ≤ 2 bowel movements (BMs) per week and/or one of the following symptoms: pebblelike, hard stool, painful defecation, encopresis). Constipation should have been treated by dietary advice for at least two weeks without improvement. Qualified subjects were randomly assigned to receive either PEG 4000 or lactulose, over a 4 weeks treatment period. The dosing were the approved dose in this class of age, i.e. PEG 4000 = 2 sachets of 4g (1 in the morning, 1 in the evening), lactulose = 1 sachet of 3.3g (in the morning) and 1 sachet of lactulose placebo (in the evening).The primary criterion was the number of Bowel Movement (BM) during the 4th week. Results: Both treatment groups in ITT population (43 in PEG 4000, 44 in lactulose) were similar in their demographic characteristics: mean (SD) age: 1.99 (± 0.50) year; constipation duration: mean (SD) 43.80 (± 25.42) weeks. Results of the number of BM/week (Mean ± SD) were respectively in PEG 4000 and lactulose: at baseline 0.5±0.5 and 0.7±0.5, at Week 4: 1.1±0.5 and 0.8±0.4. Adjusting for the BM at baseline, there was a significant difference (p=0.0005) in the number of BM during the 4th week between treatment groups in favour of the PEG 4000 group. The adjusted mean change from baseline in BM of PEG 4000 treatment (0.5117) is significantly higher than that of the lactulose treatment group (0.1479). The corresponding treatment effect estimate (0.3637, 95% CI: [0.1642, 0.5633]) is statistically significant (p= 0.0005). The number of TEAEs considered possibly or probably related to the study drug is comparable in both treatment groups. All of the SAEs recorded were considered not related to the study drugs. Conclusion: PEG 4000 has a better efficacy than lactulose for the treatment of chronic constipation in Asiatic children.
Background/Aims: This study was aimed to evaluate the effects and the optimal dosage of combination therapy of probiotics and mosapride compared with placebo in patients with irritable bowel syndrome (IBS) without diarrhea. Methods: In phase 2, randomized, doubleblind, placebo-controlled, multicenter trials, 287 patients who had IBS without diarrhea were randomly assigned to either combination of probiotics (Bacillus subtilis and Streptococcus faecium) and mosapride at four different doses or placebo, three times daily for 4 weeks after 1-week baseline period, and were followed for an additional 2 weeks. The treatment group 4 had the highest dose (probiotics 3 x 1010 CFU and mosapride 15 mg per day), followed by treatment group 3, 2, and 1. The primary end point was the proportion of patients who had adequate relief (AR) of global IBS symptoms at week 4. The secondary end point included the subject's global assessment of IBS symptom relief (SGA, range 15) assessed weekly and individual symptoms (5-point Likert score) and stool parameters (consistency and frequency) as assessed by daily self-ratings during the whole study period. IBS quality of life (IBS-QOL) was assessed at the beginning and at the end of the treatment. Results: The mean age of the enrolled patients were 47.0±13.5 and male gender was 49.8% (43/287). There was no difference in the baseline characteristics between the groups. Significantly more patients in the treatment groups than in the placebo group had AR of global IBS symptoms at week 4 regardless of the doses (53.6% in treatment 1, 55.0% in treatment 2, 55.2% in treatment 3, and 53.6% in treatment 4 vs. 35.1% in placebo, P , 0.05, respectively). The proportion of patients in whom the symptoms were completely disappeared or much improved in SGA was significantly higher in the treatment groups than in the placebo group. The improvement of abdominal pain/discomfort was significantly greater in the treatment group 4, the highest dose group, compared to the placebo group. The improvements of the other symptoms tended to higher in the treatment groups without statistical significance. In the constipation-predominant IBS (C-IBS) subgroup, spontaneous complete bowel movements per week and Bristol Stool Scale scores increased more prominently in the treatment groups than in the placebo group. The IBS-QOL tended to improve more in the treatment groups without statistical significance. No significant adverse events were recorded. Conclusion: Combination therapy of probiotics and mosapride was safe and effective for providing relief of symptoms in IBS without diarrhea, and the benefit was greatest at a dose of probiotics 3 x 1010 CFU and mosapride 15 mg per day. These results warrant further study of the combination therapy of probiotics and mosapride for treatment of IBS without constipation.
Su2067 Results of Gastric Emptying Tested With Wireless Motility Capsule in Chronic Constipation Patients Before and After Lubiprostone Irene Sarosiek, Alicia Alvarez, Roberta Romero, Yvette Gomez, Natalia Vega, Richard W. McCallum, Jerzy Sarosiek Background: Lubiprostone is a highly selective and novel ClC-2 activator approved for chronic constipation (CC). A well recognized part of its adverse event profile is nausea being reported in up to 30% of patients receiving 24mcg dose of drug twice daily .Delayed gastric emptying (GET) could be one reason for the presence of nausea, which is decreased when lubiprostone is administered with food. It is published that CC subjects have significantly slower GET when compared with healthy controls (Rao; Clin Gastro&Hep 2009;7:537544). The addition of a ClC-2 activator in this CC population of patients needs further study to understand changes in GET and implications for nausea. Aim: To investigate the influence of lubiprostone on gastric emptying rate measured by wireless motility capsule (WMC) in patients diagnosed with CC based on Rome III criteria. Methods: GET results were obtained from 29 female (15 Caucasian-C, 14 Hispanic-H) CC patients [mean age 39 (19-64); mean weight 169 lbs (11-305)]. All subjects underwent testing with WMC before treatment and on day number 8 of therapy with 24mcg BID of lubiprostone. GET was defined as the time interval between ingestion of the capsule and the time point when there was an abrupt rise of . 2 units of pH to reach .6.0 units reflecting passage of WMC from the acidic stomach to the alkaline duodenum. Statistical analysis, using Shapiro-Wilk or Mann-Whitney Rank Sum Test on data was performed using Sigma-Stat software. Results: Nine (30%) (1C-7% and 8H-57%) of 29 subjects had slow GE at baseline defined as .5 hrs by WMC methodology with their mean GET before the treatment of 14.3h and 16.2h after therapy with lubiprostone , a 13% increase (NS).Two (22%) of them complained about mild nausea after taking medication on an empty stomach. The median value of 20 GETs obtained at baseline with GE ,5 hrs was 2.46 h (2.16-3.49) and it was slowed to 3.29 h (2.25-4.9) after lubiprostone, i.e. by 69% (P=0.140). 15 of these CC patients (75%) showed prolongation of GET after lubiprostone while the remaining 5 patients recorded shorter times of GETs. Specifically for patients whose GET slowed after lubiprostone, the median GET was 2.33h (2.03-3.05) at baseline and it increased by 83% to 4.2h (2.3-5.39) after lubiprostone showing significance (P=0.019). Three of these patients (15%) admitted to have nausea in the mornings with lubiprostone dosing before breakfast, but it did not require any clinical attention or discontinuation of the study drug. Conclusions: 1) GET can be slow in up to 30% of patients with chronic constipation and this observation is relevant to the interpretation of GET results in the clinical setting. 2) There was a modest slowing of GET with lubiprostone and we suggest that this change in GET is not sufficient to explain the nausea side effect profile of this drug.
Su2069 How Effective Is Prucalopride for the Treatment of Chronic Constipation? A Systematic Review and Meta-Analysis Luigi Gatta, René Kerstens, Carmelo Scarpignato Background: Chronic constipation (CC) is a challenging, albeit common, condition that impairs quality of life and, because of its high prevalence and chronicity, consumes significant healthcare resources. Our understanding of the pathophysiology of constipation remains incomplete, and available therapies have limited efficacy. Prucalopride is the first selective, high-affinity 5-HT4 agonist, with a predominantly enterokinetic effect, translating into a significant clinical efficacy. Aim: To perform a systematic review and meta-analysis of the large clinical trials using prucalopride to treat patients affected by CC in order to assess its efficacy. Methods: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials as well as abstracts from the major American, European and Asian meetings were searched up to November 2012. Large ( ≥ 250 patients) randomized controlled trials (RCTs) in adult patients with CC, treated with prucalopride, were included. Risk of bias for RCTs was assessed as described in the Cochrane handbook. Relative risks (with 95% CI) were computed using a random effects model in order to provide a more conservative estimate. The outcomes assessed were the number of patients with an average increase of ≥3 SCBM (at both 4 and 12 weeks), the number of patients with an average increase of ≥1 SCBM (at 12 weeks), the number of patients rating their treatment as extremely or quite a bit effective, the Improvement ≥1 PAC-SYM satisfaction from baseline as well as the use of laxative (both oral and enemas). Results were analyzed only if, for each variable considered, data were available from at least 3 RCTs. Results: Five studies, comparing different doses of prucalopride to placebo, were identified. They included more than 2500 patients, most (up to 92.5 %) of whom were female. All studies were at low risks of bias. The results are shown in Table 1. Conclusions: Prucalopride is effective for treating CC and also improves significantly the quality of life. The two regimens tested (i.e. 2 mg and 4 mg daily) provide a similar clinical benefit, with no evidence of dose-response effect. Table 1.
S-547
AGA Abstracts
AGA Abstracts
Su2066
Efficacy of a Polyethylene Glycol Laxative (PEG, Macrogol 4000) Versus Lactulose for the Treatment of Chronic Constipation in Children. Results of a Randomized, Double-Blind Controlled Study Performed in Thailand Suporn Treepongkaruna, Nipat Simakachorn, Paneeya Pienvichit, Axel Magis, Philippe Garnier, Pascal Maisonobe, Hélène Mathiex-Fortunet
Efficacy of Combination Therapy of Probiotics and Mosapride in Patients With IBS Without Diarrhea: Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Trial Chang Hwan Choi, Joong Goo Kwon, Sung-Kook Kim, Seung-Jae Myung, Kyung Sik Park, Chong Il Sohn, Poong-Lyul Rhee, Kwang Jae Lee, Oh Young Lee, Hye-Kyung Jung, Sam Ryong Jee, Yoon Tae Jeen, Myung-Gyu Choi, Suck Chei Choi, Kyuchan Huh, Hyojin Park
Introduction: The study is the first one in Asia comparing a PEG 4000 to another osmotic laxative (lactulose) in children with chronic constipation. Patients and Methods: This randomized, double-blind, lactulose controlled study was conducted in 2 parallel groups in 2 centers in 88 children in Thailand. Male or female (outpatient) children aged between 12 to 36 months were included if they had a chronic constipation (defined as ≥ 3 months of ≤ 2 bowel movements (BMs) per week and/or one of the following symptoms: pebblelike, hard stool, painful defecation, encopresis). Constipation should have been treated by dietary advice for at least two weeks without improvement. Qualified subjects were randomly assigned to receive either PEG 4000 or lactulose, over a 4 weeks treatment period. The dosing were the approved dose in this class of age, i.e. PEG 4000 = 2 sachets of 4g (1 in the morning, 1 in the evening), lactulose = 1 sachet of 3.3g (in the morning) and 1 sachet of lactulose placebo (in the evening).The primary criterion was the number of Bowel Movement (BM) during the 4th week. Results: Both treatment groups in ITT population (43 in PEG 4000, 44 in lactulose) were similar in their demographic characteristics: mean (SD) age: 1.99 (± 0.50) year; constipation duration: mean (SD) 43.80 (± 25.42) weeks. Results of the number of BM/week (Mean ± SD) were respectively in PEG 4000 and lactulose: at baseline 0.5±0.5 and 0.7±0.5, at Week 4: 1.1±0.5 and 0.8±0.4. Adjusting for the BM at baseline, there was a significant difference (p=0.0005) in the number of BM during the 4th week between treatment groups in favour of the PEG 4000 group. The adjusted mean change from baseline in BM of PEG 4000 treatment (0.5117) is significantly higher than that of the lactulose treatment group (0.1479). The corresponding treatment effect estimate (0.3637, 95% CI: [0.1642, 0.5633]) is statistically significant (p= 0.0005). The number of TEAEs considered possibly or probably related to the study drug is comparable in both treatment groups. All of the SAEs recorded were considered not related to the study drugs. Conclusion: PEG 4000 has a better efficacy than lactulose for the treatment of chronic constipation in Asiatic children.
Background/Aims: This study was aimed to evaluate the effects and the optimal dosage of combination therapy of probiotics and mosapride compared with placebo in patients with irritable bowel syndrome (IBS) without diarrhea. Methods: In phase 2, randomized, doubleblind, placebo-controlled, multicenter trials, 287 patients who had IBS without diarrhea were randomly assigned to either combination of probiotics (Bacillus subtilis and Streptococcus faecium) and mosapride at four different doses or placebo, three times daily for 4 weeks after 1-week baseline period, and were followed for an additional 2 weeks. The treatment group 4 had the highest dose (probiotics 3 x 1010 CFU and mosapride 15 mg per day), followed by treatment group 3, 2, and 1. The primary end point was the proportion of patients who had adequate relief (AR) of global IBS symptoms at week 4. The secondary end point included the subject's global assessment of IBS symptom relief (SGA, range 15) assessed weekly and individual symptoms (5-point Likert score) and stool parameters (consistency and frequency) as assessed by daily self-ratings during the whole study period. IBS quality of life (IBS-QOL) was assessed at the beginning and at the end of the treatment. Results: The mean age of the enrolled patients were 47.0±13.5 and male gender was 49.8% (43/287). There was no difference in the baseline characteristics between the groups. Significantly more patients in the treatment groups than in the placebo group had AR of global IBS symptoms at week 4 regardless of the doses (53.6% in treatment 1, 55.0% in treatment 2, 55.2% in treatment 3, and 53.6% in treatment 4 vs. 35.1% in placebo, P , 0.05, respectively). The proportion of patients in whom the symptoms were completely disappeared or much improved in SGA was significantly higher in the treatment groups than in the placebo group. The improvement of abdominal pain/discomfort was significantly greater in the treatment group 4, the highest dose group, compared to the placebo group. The improvements of the other symptoms tended to higher in the treatment groups without statistical significance. In the constipation-predominant IBS (C-IBS) subgroup, spontaneous complete bowel movements per week and Bristol Stool Scale scores increased more prominently in the treatment groups than in the placebo group. The IBS-QOL tended to improve more in the treatment groups without statistical significance. No significant adverse events were recorded. Conclusion: Combination therapy of probiotics and mosapride was safe and effective for providing relief of symptoms in IBS without diarrhea, and the benefit was greatest at a dose of probiotics 3 x 1010 CFU and mosapride 15 mg per day. These results warrant further study of the combination therapy of probiotics and mosapride for treatment of IBS without constipation.
Su2067 Results of Gastric Emptying Tested With Wireless Motility Capsule in Chronic Constipation Patients Before and After Lubiprostone Irene Sarosiek, Alicia Alvarez, Roberta Romero, Yvette Gomez, Natalia Vega, Richard W. McCallum, Jerzy Sarosiek Background: Lubiprostone is a highly selective and novel ClC-2 activator approved for chronic constipation (CC). A well recognized part of its adverse event profile is nausea being reported in up to 30% of patients receiving 24mcg dose of drug twice daily .Delayed gastric emptying (GET) could be one reason for the presence of nausea, which is decreased when lubiprostone is administered with food. It is published that CC subjects have significantly slower GET when compared with healthy controls (Rao; Clin Gastro&Hep 2009;7:537544). The addition of a ClC-2 activator in this CC population of patients needs further study to understand changes in GET and implications for nausea. Aim: To investigate the influence of lubiprostone on gastric emptying rate measured by wireless motility capsule (WMC) in patients diagnosed with CC based on Rome III criteria. Methods: GET results were obtained from 29 female (15 Caucasian-C, 14 Hispanic-H) CC patients [mean age 39 (19-64); mean weight 169 lbs (11-305)]. All subjects underwent testing with WMC before treatment and on day number 8 of therapy with 24mcg BID of lubiprostone. GET was defined as the time interval between ingestion of the capsule and the time point when there was an abrupt rise of . 2 units of pH to reach .6.0 units reflecting passage of WMC from the acidic stomach to the alkaline duodenum. Statistical analysis, using Shapiro-Wilk or Mann-Whitney Rank Sum Test on data was performed using Sigma-Stat software. Results: Nine (30%) (1C-7% and 8H-57%) of 29 subjects had slow GE at baseline defined as .5 hrs by WMC methodology with their mean GET before the treatment of 14.3h and 16.2h after therapy with lubiprostone , a 13% increase (NS).Two (22%) of them complained about mild nausea after taking medication on an empty stomach. The median value of 20 GETs obtained at baseline with GE ,5 hrs was 2.46 h (2.16-3.49) and it was slowed to 3.29 h (2.25-4.9) after lubiprostone, i.e. by 69% (P=0.140). 15 of these CC patients (75%) showed prolongation of GET after lubiprostone while the remaining 5 patients recorded shorter times of GETs. Specifically for patients whose GET slowed after lubiprostone, the median GET was 2.33h (2.03-3.05) at baseline and it increased by 83% to 4.2h (2.3-5.39) after lubiprostone showing significance (P=0.019). Three of these patients (15%) admitted to have nausea in the mornings with lubiprostone dosing before breakfast, but it did not require any clinical attention or discontinuation of the study drug. Conclusions: 1) GET can be slow in up to 30% of patients with chronic constipation and this observation is relevant to the interpretation of GET results in the clinical setting. 2) There was a modest slowing of GET with lubiprostone and we suggest that this change in GET is not sufficient to explain the nausea side effect profile of this drug.
Su2069 How Effective Is Prucalopride for the Treatment of Chronic Constipation? A Systematic Review and Meta-Analysis Luigi Gatta, René Kerstens, Carmelo Scarpignato Background: Chronic constipation (CC) is a challenging, albeit common, condition that impairs quality of life and, because of its high prevalence and chronicity, consumes significant healthcare resources. Our understanding of the pathophysiology of constipation remains incomplete, and available therapies have limited efficacy. Prucalopride is the first selective, high-affinity 5-HT4 agonist, with a predominantly enterokinetic effect, translating into a significant clinical efficacy. Aim: To perform a systematic review and meta-analysis of the large clinical trials using prucalopride to treat patients affected by CC in order to assess its efficacy. Methods: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials as well as abstracts from the major American, European and Asian meetings were searched up to November 2012. Large ( ≥ 250 patients) randomized controlled trials (RCTs) in adult patients with CC, treated with prucalopride, were included. Risk of bias for RCTs was assessed as described in the Cochrane handbook. Relative risks (with 95% CI) were computed using a random effects model in order to provide a more conservative estimate. The outcomes assessed were the number of patients with an average increase of ≥3 SCBM (at both 4 and 12 weeks), the number of patients with an average increase of ≥1 SCBM (at 12 weeks), the number of patients rating their treatment as extremely or quite a bit effective, the Improvement ≥1 PAC-SYM satisfaction from baseline as well as the use of laxative (both oral and enemas). Results were analyzed only if, for each variable considered, data were available from at least 3 RCTs. Results: Five studies, comparing different doses of prucalopride to placebo, were identified. They included more than 2500 patients, most (up to 92.5 %) of whom were female. All studies were at low risks of bias. The results are shown in Table 1. Conclusions: Prucalopride is effective for treating CC and also improves significantly the quality of life. The two regimens tested (i.e. 2 mg and 4 mg daily) provide a similar clinical benefit, with no evidence of dose-response effect. Table 1.
S-547
AGA Abstracts
AGA Abstracts
Su2066