- Email: [email protected]
Su1584 Colonic Motor Responses to a Meal and to Bisacodyl, Evaluated by High-Resolution Manometry (HRM), Differ Between Laxative-Refractory Slow Transit Constipation With or Without Pain
Data expressed as number (percentage) # Chi-square test. SIBO: small intestinal bacterial overgrowth; OCTT: orocecal transit time; FC: functional constipation.
Figure 2 The effects of Mashiningan on dried fecal weight in opioid-stimulant induced constipation in rats
Su1582 Factors that Predict Outcomes to Prucalopride Sheeba Khan, Sarah Hoole, Alan Bohan, Adam D. Farmer Introduction- Chronic idiopathic constipation (CIC) is a prevalent disorder with traditional management focussing on lifestyle measures and laxatives. Prucalopride, a selective 5-HT4 receptor agonist, has efficacy in treatment of CIC. However, factors that predict clinical response are incompletely understood. Aims- To identification of baseline factors, either physiological or psychological, that may predict positive clinical outcomes in patients taking prucalopride for CIC in a secondary care clinic. Methods- A single centre, prospective open label trial was undertaken in consecutive patients with CC, defined as less than 2 spontaneous complete bowel movements (SCBM) per week, who were commenced on prucalopride from November 2011-October 2015. Validated questionnaires were used to assess the severity of symptoms (patient assessment of constipation symptoms (PAC-SYM)), somatic symptoms (patient health questionnaire-12), anxiety/depression and the personality traits of neuroticism and extroversion (big five inventory-neuroticism or extroversion scale (BFI-N and BFI-E)). Patients were excluded if they did not wish to complete the questionnaires. Other investigations, such as colonic transit studies (CTS), were undertaken as clinically appropriate. At follow up, clinical response was defined as the proportion of patients achieving 3 or more SCBM per week. Results- 70 patients (68 female, mean age 48 years, range 18-83) had a mean SCBM per week of 1.7 (range 0.5-2). At a mean follow up of 5.1 weeks (range 4-8) 32/70 (45.7%) patients achieved clinical response. 9/70 (12.8%) did not tolerate treatment due to side effects. In an intention to treat analysis, SCBM per week increased from 1.7 to 3.2 (p=0.01) with PAC-SYM scores reducing from 27.5 to 19 ( p=0.001). Significant variables from logistic regression analysis, are shown in table 1. Conclusions- These data suggest that the clinical efficacy of prucalopride could be enhanced by targeting patients who are more neurotic and higher somatic symptoms. The personality trait of neuroticism has been associated with differential expression of the serotonin transporter which could explain this association. Nevertheless, the underlying mechanisms for this association and warrant further investigation. Table 1 - Logistic regression analysis of the factors that predict response to prucalopride
Su1584 Colonic Motor Responses to a Meal and to Bisacodyl, Evaluated by HighResolution Manometry (HRM), Differ Between Laxative-Refractory Slow Transit Constipation With or Without Pain Maura Corsetti, Alexander Thys, Tim Vanuytsel, Ingrid Demedts, Albert Wolthuis, Andre D'Hoore, Jan F. Tack In clinical practice colonic manometry is recommended to exclude colonic inertia (no response to meal and to drug stimulation, i.e. bisacodyl) in patients with slow transit constipation not responsive to laxatives (Bharucha 2013). As to date, this has not been assessed by colonic HRM in adults, our aim was to evaluate the colonic motor response to a meal and to bisacodyl in patients with slow-transit constipation not responsive to laxatives. Methods: Consecutive patients with slow-transit and Rome III constipation resistant to laxatives were enrolled. After an overnight fast and tap water enema preparation, during colonoscopy under conscious sedation, an HRM catheter (40 sensors, 2.5 cm spaced) and an infusion tube were advanced as far as possible (caecum) and clipped to the mucosa. Colonic pressures were recorded for three hours before and two after a standardized meal, and for one hour after intra-colonic administration of bisacodyl (10 mg). Number of pancolonic pressurizations (defined by Corsetti 2015) and of low-amplitude (LAPSs, defined by Dinning 2014) and high-amplitude propagating sequences (HAPSs, defined by De Schryver 2002) were evaluated. A normal response to bisacodyl was identified by the occurrence of at least one HAPS. Data (mean±SD) were compared with those obtained in 10 healthy subjects (HS) (30±11 years, 5 females). Results: A total of 17 refractory slowtransit constipation patients (43±13 years, 15 females) were studied; 9 of these also referred the presence of pain or discomfort. The total number of pan-colonic pressurizations was significantly lower in patients as a group and in patients without pain as compared to HS (respectively, 32±35 and 9±19 vs 89±40, all p<0.001), while it did not differ in patients with pain (53±35). The total number of LAPSs did not differ in patients as a group (25±29) and in patients with pain (40±30), but was significantly lower in patients without pain as compared to HS (6±10 vs 52±39, p=0.009). Pan-colonic pressurizations significantly increased after a meal in HS and in patients with (p<0.02) but not in those without pain (p=0.49). Retrograde LAPSs increased significantly after the meal in HS (p=0.01) but not in patients, regardless of the presence of pain (all p>0.30). The response to bisacodyl was normal in 8/9 (88%) patients with pain and in 2/8 (25%) of those without pain (p=0.01, Fisher's test). Abnormal responses to bisacodyl included absence of contractions, repetitive pan- or distal- colonic pressurizations or atypical HAPSs (Figures). Conclusions: Approximately 50% of patients with laxative-refractory slow-transit constipation also present with abdominal pain. Compared to slow transit patients without pain, these patients have a partially preserved response to meal (increased pan-colonic pressurizations but not LAPSs) and a higher prevalence of a normal response to bisacodyl.
Su1583 The Prevalence of Delayed Orocecal Transit Time and Small Intestinal Bacterial Overgrowth in Patients With Functional Constipation Ting Yu, Lin Lin Background & Aims: Disordered colon motility is an important cause of functional constipation (FC). In addition to prolonged time between bowel movements, patients typically experience abdominal distension, bloating, and discomfort. Recently, the association of concurrent small intestinal dysmotility has been increasingly studied and reported. Besides, it is widely recognized that delayed orocecal transit time (OCTT) predisposes to small bowel bacterial overgrowth (SIBO), which may result in different clinical effects, like bloating, flatulence and abdominal pain. We aimed to study frequency of SIBO and delayed OCTT, and to detect relationship between colon transit and orocecal transit, SIBO in FC patients. Methods: Thirty FC patients and 20 healthy controls were enrolled. All subjects underwent hydrogen breath test to assess SIBO and OCTT. The FC patients performed a visual analog scale to investigate abdominal pain, bloating and flatulence, and maintained a diary of the frequency and consistency of the stool during the previous 7 days. Colon transit time (CTT) test were performed for FC patients. Results: SIBO and delayed OCTT was more frequent in patients with FC than healthy controls (43.1% vs 5.7%, P < 0.001; 68.4% vs 3.2%, P < 0.001). FC patients atients with SIBO showed a higher visual analog scale score of abdominal
S-533
X : 10052$CH01 03-28-16 00:57:27 PDFd : 10052B : o
Page 533
AGA Abstracts
AGA Abstracts
pain (3.9 ± 1.1 vs 2.1 ± 1.5, P = 0.031), bloating (4.4 ± 1.5 vs 3.4 ± 1.8, P = 0.073) and flatulence (3.9 ± 1.0 vs 2.5 ± 0.8; P = 0.041) compared with those without SIBO. Twenty one patient had delayed CTT, and these patients showed significantly higher frequency of SIBO (P = 0.011) and delayed OCTT ( P < 0.001) compared with those with normal CTT. Conclusions: SIBO and delayed OCTT was more frequent in patients with FC as compared to healthy controls. SIBO may aggravate abdominal symptoms in FC patients. The association between delayed CTT and SIBO suggests that colon dysmotility has an active role in the development of SIBO. The concurrent of delayed CTT and OCTT indicated that FC is a disease charactered with a whole gastrointestinal dysmotility. Comparision of presence of SIBO and delayed OCTT between healthy volunteers and FC patients
Su1586
AGA Abstracts
Lubiprostone Responder Rates in Patients With Chronic Idiopathic Constipation: Increased Frequencyoof Spontaneous Bowel Movements and Improved Constipation-Related Symptoms Shadreck M. Mareya, Martin Wang, Taryn Losch-Beridon, Peter Lichtlen Background: Lubiprostone, a type 2 chloride channel (ClC-2) activator, is indicated for the treatment of chronic idiopathic constipation (CIC) in adults. A post hoc analysis of data from 3 clinical trials examined the response to lubiprostone using criteria recommended by the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP)—increased frequency of bowel movements for 75% of treatment weeks. Lubiprostone responses with regard to improvement in stool consistency and straining with defecation are also reported. Methods: Data (pooled and analyzed separately for each study) were from 3 trials conducted in the US or Japan in adults with CIC who were randomized to doubleblind lubiprostone (24 mcg twice daily) or placebo for 4 weeks. Responders had ‡3 spontaneous bowel movements (SBMs)/week and an increase of ‡1 SBM/week compared with baseline for 3 of the 4 treatment weeks. Sensitivity analyses with varying SBM response definitions were performed to test the robustness of these results, including one that required fulfillment of SBM frequency criteria for all 4 treatment weeks. Stool consistency was assessed on a 5-point (Studies 1 and 2) or 7-point scale (Study 3) .Straining with defecation was assessed on a 5-point scale from 0 (absent) to 4 (very severe). Responders for stool consistency or straining had a 1-unit improvement from baseline on respective scales each week for ‡3 of 4 treatment weeks. Results: The mean age (pooled population [n=603]) was 46 years; 89% of patients were female; and most were white (64%) or Asian (22%). A significantly higher proportion of patients (pooled analysis) who received lubiprostone vs placebo were SBM responders, meeting response criteria for 3 of 4 treatment weeks ( P<0.0001). A similar proportion of patients who received lubiprostone vs placebo were SBM responders for all 4 treatment weeks (P<0.0001; Table 1). Significant results were observed for both response definitions in Studies 1 and 3; in Study 2, the treatment effect was significant only when criteria required the response to be met for all 4 treatment weeks. Lubiprostone treatment vs placebo was associated with significantly higher rates of improved stool consistency in analyses of pooled data and individual studies. Significantly less straining was found for lubiprostone vs placebo in the analysis of pooled data and for Study 1 (Table 2). Conclusions: Analyses of pooled data demonstrated that lubiprostone treatment was associated with significantly higher SBM response rates vs placebo, using EMA/CHMP-recommended criteria. Responder rates were also significantly higher with lubiprostone when SBM frequency criteria were applied for all 4 treatment weeks. Further, lubiprostone was associated with improvements in clinically relevant symptoms of stool consistency and straining. Table 1. Lubiprostone SBM* Responder Analysis in Patients With CIC in 3 Clinical Trials
Su1585 Lubiprostone Responder Rates in Patients With Opioid-Induced Constipation: Increased Frequency of Complete Spontaneous Bowel Movements Taryn Losch-Beridon, Shadreck M. Mareya, Martin Wang, Peter Lichtlen Background: Lubiprostone is a ClC-2 chloride channel activator that is indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain. A significant increase from baseline in the frequency of spontaneous bowel movements (SBMs) after 8 weeks of lubiprostone administration was found in 1 of 2 studies that allowed the use of any opioid for treatment of chronic non-cancer pain. A third trial excluded patients receiving methadone or a methadone congener; in that study, lubiprostone treatment resulted in a significant SBM response (defined as ‡1 SBM for all treatment weeks and ‡3 SBMs/ week for ‡9 of 12 treatment weeks). Here we report a post hoc analysis of pooled data that examines the response to lubiprostone using criteria from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP), which recommends a primary endpoint based on complete SBMs (CSBMs). Methods: Data were pooled from three phase 3 studies in which patients with OIC were randomized to receive lubiprostone (24 mcg twice daily) or placebo for 12 weeks. Overall responders had ‡9 weeks of nonmissing CSBM frequency data and a response for 75% of treatment weeks, including ‡3 of the final 4 weeks. Three definitions of weekly CSBM response were evaluated: ‡3 CSBMs/ week and an increase from baseline of ‡1 CSBM/week (the EMA/CHMP recommendation); an increase from baseline of ‡1 CSBM/week; and an increase from baseline of ‡2 CSBMs/ week. Results: Patients in the pooled population (n=1312) had a mean age of 50 years; 63% were women, and most were Caucasian (83%) or black (14%). Baseline characteristics were similar in patients who received lubiprostone treatment or placebo. The overall responder rate based on the EMA/CHMP definition was significantly higher in patients treated with lubiprostone compared with placebo (Figure 1). A sensitivity analysis using the other definitions of a weekly response yielded qualitatively similar results (Figure 1). Conclusions: Pooled data from three phase 3 studies demonstrated that lubiprostone treatment is associated with a significantly higher response rate vs placebo, using EMA/CHMPrecommended CSBM-based response criteria. A sensitivity analysis using 2 additional response definitions based on CSBM frequency also demonstrated a significant effect of lubiprostone vs placebo on response rate.
AGA Abstracts
X : 10052$CH01 03-28-16 00:57:27 PDFd : 10052B : e
CI=confidence interval; CIC=chronic idiopathic constipation; SBM= spontaneous bowel movement. *SBM response criteria: ‡3 observed SBMs/week and an increase from baseline of ‡1 SBM/week. Table 2. Lubiprostone Responder Rates for Improvement in CIC Symptoms in Patients in 3 Clinical Trials
S-534
Page 534
Figure 2 The effects of Mashiningan on dried fecal weight in opioid-stimulant induced constipation in rats
Su1582 Factors that Predict Outcomes to Prucalopride Sheeba Khan, Sarah Hoole, Alan Bohan, Adam D. Farmer Introduction- Chronic idiopathic constipation (CIC) is a prevalent disorder with traditional management focussing on lifestyle measures and laxatives. Prucalopride, a selective 5-HT4 receptor agonist, has efficacy in treatment of CIC. However, factors that predict clinical response are incompletely understood. Aims- To identification of baseline factors, either physiological or psychological, that may predict positive clinical outcomes in patients taking prucalopride for CIC in a secondary care clinic. Methods- A single centre, prospective open label trial was undertaken in consecutive patients with CC, defined as less than 2 spontaneous complete bowel movements (SCBM) per week, who were commenced on prucalopride from November 2011-October 2015. Validated questionnaires were used to assess the severity of symptoms (patient assessment of constipation symptoms (PAC-SYM)), somatic symptoms (patient health questionnaire-12), anxiety/depression and the personality traits of neuroticism and extroversion (big five inventory-neuroticism or extroversion scale (BFI-N and BFI-E)). Patients were excluded if they did not wish to complete the questionnaires. Other investigations, such as colonic transit studies (CTS), were undertaken as clinically appropriate. At follow up, clinical response was defined as the proportion of patients achieving 3 or more SCBM per week. Results- 70 patients (68 female, mean age 48 years, range 18-83) had a mean SCBM per week of 1.7 (range 0.5-2). At a mean follow up of 5.1 weeks (range 4-8) 32/70 (45.7%) patients achieved clinical response. 9/70 (12.8%) did not tolerate treatment due to side effects. In an intention to treat analysis, SCBM per week increased from 1.7 to 3.2 (p=0.01) with PAC-SYM scores reducing from 27.5 to 19 ( p=0.001). Significant variables from logistic regression analysis, are shown in table 1. Conclusions- These data suggest that the clinical efficacy of prucalopride could be enhanced by targeting patients who are more neurotic and higher somatic symptoms. The personality trait of neuroticism has been associated with differential expression of the serotonin transporter which could explain this association. Nevertheless, the underlying mechanisms for this association and warrant further investigation. Table 1 - Logistic regression analysis of the factors that predict response to prucalopride
Su1584 Colonic Motor Responses to a Meal and to Bisacodyl, Evaluated by HighResolution Manometry (HRM), Differ Between Laxative-Refractory Slow Transit Constipation With or Without Pain Maura Corsetti, Alexander Thys, Tim Vanuytsel, Ingrid Demedts, Albert Wolthuis, Andre D'Hoore, Jan F. Tack In clinical practice colonic manometry is recommended to exclude colonic inertia (no response to meal and to drug stimulation, i.e. bisacodyl) in patients with slow transit constipation not responsive to laxatives (Bharucha 2013). As to date, this has not been assessed by colonic HRM in adults, our aim was to evaluate the colonic motor response to a meal and to bisacodyl in patients with slow-transit constipation not responsive to laxatives. Methods: Consecutive patients with slow-transit and Rome III constipation resistant to laxatives were enrolled. After an overnight fast and tap water enema preparation, during colonoscopy under conscious sedation, an HRM catheter (40 sensors, 2.5 cm spaced) and an infusion tube were advanced as far as possible (caecum) and clipped to the mucosa. Colonic pressures were recorded for three hours before and two after a standardized meal, and for one hour after intra-colonic administration of bisacodyl (10 mg). Number of pancolonic pressurizations (defined by Corsetti 2015) and of low-amplitude (LAPSs, defined by Dinning 2014) and high-amplitude propagating sequences (HAPSs, defined by De Schryver 2002) were evaluated. A normal response to bisacodyl was identified by the occurrence of at least one HAPS. Data (mean±SD) were compared with those obtained in 10 healthy subjects (HS) (30±11 years, 5 females). Results: A total of 17 refractory slowtransit constipation patients (43±13 years, 15 females) were studied; 9 of these also referred the presence of pain or discomfort. The total number of pan-colonic pressurizations was significantly lower in patients as a group and in patients without pain as compared to HS (respectively, 32±35 and 9±19 vs 89±40, all p<0.001), while it did not differ in patients with pain (53±35). The total number of LAPSs did not differ in patients as a group (25±29) and in patients with pain (40±30), but was significantly lower in patients without pain as compared to HS (6±10 vs 52±39, p=0.009). Pan-colonic pressurizations significantly increased after a meal in HS and in patients with (p<0.02) but not in those without pain (p=0.49). Retrograde LAPSs increased significantly after the meal in HS (p=0.01) but not in patients, regardless of the presence of pain (all p>0.30). The response to bisacodyl was normal in 8/9 (88%) patients with pain and in 2/8 (25%) of those without pain (p=0.01, Fisher's test). Abnormal responses to bisacodyl included absence of contractions, repetitive pan- or distal- colonic pressurizations or atypical HAPSs (Figures). Conclusions: Approximately 50% of patients with laxative-refractory slow-transit constipation also present with abdominal pain. Compared to slow transit patients without pain, these patients have a partially preserved response to meal (increased pan-colonic pressurizations but not LAPSs) and a higher prevalence of a normal response to bisacodyl.
Su1583 The Prevalence of Delayed Orocecal Transit Time and Small Intestinal Bacterial Overgrowth in Patients With Functional Constipation Ting Yu, Lin Lin Background & Aims: Disordered colon motility is an important cause of functional constipation (FC). In addition to prolonged time between bowel movements, patients typically experience abdominal distension, bloating, and discomfort. Recently, the association of concurrent small intestinal dysmotility has been increasingly studied and reported. Besides, it is widely recognized that delayed orocecal transit time (OCTT) predisposes to small bowel bacterial overgrowth (SIBO), which may result in different clinical effects, like bloating, flatulence and abdominal pain. We aimed to study frequency of SIBO and delayed OCTT, and to detect relationship between colon transit and orocecal transit, SIBO in FC patients. Methods: Thirty FC patients and 20 healthy controls were enrolled. All subjects underwent hydrogen breath test to assess SIBO and OCTT. The FC patients performed a visual analog scale to investigate abdominal pain, bloating and flatulence, and maintained a diary of the frequency and consistency of the stool during the previous 7 days. Colon transit time (CTT) test were performed for FC patients. Results: SIBO and delayed OCTT was more frequent in patients with FC than healthy controls (43.1% vs 5.7%, P < 0.001; 68.4% vs 3.2%, P < 0.001). FC patients atients with SIBO showed a higher visual analog scale score of abdominal
S-533
X : 10052$CH01 03-28-16 00:57:27 PDFd : 10052B : o
Page 533
AGA Abstracts
AGA Abstracts
pain (3.9 ± 1.1 vs 2.1 ± 1.5, P = 0.031), bloating (4.4 ± 1.5 vs 3.4 ± 1.8, P = 0.073) and flatulence (3.9 ± 1.0 vs 2.5 ± 0.8; P = 0.041) compared with those without SIBO. Twenty one patient had delayed CTT, and these patients showed significantly higher frequency of SIBO (P = 0.011) and delayed OCTT ( P < 0.001) compared with those with normal CTT. Conclusions: SIBO and delayed OCTT was more frequent in patients with FC as compared to healthy controls. SIBO may aggravate abdominal symptoms in FC patients. The association between delayed CTT and SIBO suggests that colon dysmotility has an active role in the development of SIBO. The concurrent of delayed CTT and OCTT indicated that FC is a disease charactered with a whole gastrointestinal dysmotility. Comparision of presence of SIBO and delayed OCTT between healthy volunteers and FC patients
Su1586
AGA Abstracts
Lubiprostone Responder Rates in Patients With Chronic Idiopathic Constipation: Increased Frequencyoof Spontaneous Bowel Movements and Improved Constipation-Related Symptoms Shadreck M. Mareya, Martin Wang, Taryn Losch-Beridon, Peter Lichtlen Background: Lubiprostone, a type 2 chloride channel (ClC-2) activator, is indicated for the treatment of chronic idiopathic constipation (CIC) in adults. A post hoc analysis of data from 3 clinical trials examined the response to lubiprostone using criteria recommended by the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP)—increased frequency of bowel movements for 75% of treatment weeks. Lubiprostone responses with regard to improvement in stool consistency and straining with defecation are also reported. Methods: Data (pooled and analyzed separately for each study) were from 3 trials conducted in the US or Japan in adults with CIC who were randomized to doubleblind lubiprostone (24 mcg twice daily) or placebo for 4 weeks. Responders had ‡3 spontaneous bowel movements (SBMs)/week and an increase of ‡1 SBM/week compared with baseline for 3 of the 4 treatment weeks. Sensitivity analyses with varying SBM response definitions were performed to test the robustness of these results, including one that required fulfillment of SBM frequency criteria for all 4 treatment weeks. Stool consistency was assessed on a 5-point (Studies 1 and 2) or 7-point scale (Study 3) .Straining with defecation was assessed on a 5-point scale from 0 (absent) to 4 (very severe). Responders for stool consistency or straining had a 1-unit improvement from baseline on respective scales each week for ‡3 of 4 treatment weeks. Results: The mean age (pooled population [n=603]) was 46 years; 89% of patients were female; and most were white (64%) or Asian (22%). A significantly higher proportion of patients (pooled analysis) who received lubiprostone vs placebo were SBM responders, meeting response criteria for 3 of 4 treatment weeks ( P<0.0001). A similar proportion of patients who received lubiprostone vs placebo were SBM responders for all 4 treatment weeks (P<0.0001; Table 1). Significant results were observed for both response definitions in Studies 1 and 3; in Study 2, the treatment effect was significant only when criteria required the response to be met for all 4 treatment weeks. Lubiprostone treatment vs placebo was associated with significantly higher rates of improved stool consistency in analyses of pooled data and individual studies. Significantly less straining was found for lubiprostone vs placebo in the analysis of pooled data and for Study 1 (Table 2). Conclusions: Analyses of pooled data demonstrated that lubiprostone treatment was associated with significantly higher SBM response rates vs placebo, using EMA/CHMP-recommended criteria. Responder rates were also significantly higher with lubiprostone when SBM frequency criteria were applied for all 4 treatment weeks. Further, lubiprostone was associated with improvements in clinically relevant symptoms of stool consistency and straining. Table 1. Lubiprostone SBM* Responder Analysis in Patients With CIC in 3 Clinical Trials
Su1585 Lubiprostone Responder Rates in Patients With Opioid-Induced Constipation: Increased Frequency of Complete Spontaneous Bowel Movements Taryn Losch-Beridon, Shadreck M. Mareya, Martin Wang, Peter Lichtlen Background: Lubiprostone is a ClC-2 chloride channel activator that is indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain. A significant increase from baseline in the frequency of spontaneous bowel movements (SBMs) after 8 weeks of lubiprostone administration was found in 1 of 2 studies that allowed the use of any opioid for treatment of chronic non-cancer pain. A third trial excluded patients receiving methadone or a methadone congener; in that study, lubiprostone treatment resulted in a significant SBM response (defined as ‡1 SBM for all treatment weeks and ‡3 SBMs/ week for ‡9 of 12 treatment weeks). Here we report a post hoc analysis of pooled data that examines the response to lubiprostone using criteria from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP), which recommends a primary endpoint based on complete SBMs (CSBMs). Methods: Data were pooled from three phase 3 studies in which patients with OIC were randomized to receive lubiprostone (24 mcg twice daily) or placebo for 12 weeks. Overall responders had ‡9 weeks of nonmissing CSBM frequency data and a response for 75% of treatment weeks, including ‡3 of the final 4 weeks. Three definitions of weekly CSBM response were evaluated: ‡3 CSBMs/ week and an increase from baseline of ‡1 CSBM/week (the EMA/CHMP recommendation); an increase from baseline of ‡1 CSBM/week; and an increase from baseline of ‡2 CSBMs/ week. Results: Patients in the pooled population (n=1312) had a mean age of 50 years; 63% were women, and most were Caucasian (83%) or black (14%). Baseline characteristics were similar in patients who received lubiprostone treatment or placebo. The overall responder rate based on the EMA/CHMP definition was significantly higher in patients treated with lubiprostone compared with placebo (Figure 1). A sensitivity analysis using the other definitions of a weekly response yielded qualitatively similar results (Figure 1). Conclusions: Pooled data from three phase 3 studies demonstrated that lubiprostone treatment is associated with a significantly higher response rate vs placebo, using EMA/CHMPrecommended CSBM-based response criteria. A sensitivity analysis using 2 additional response definitions based on CSBM frequency also demonstrated a significant effect of lubiprostone vs placebo on response rate.
AGA Abstracts
X : 10052$CH01 03-28-16 00:57:27 PDFd : 10052B : e
CI=confidence interval; CIC=chronic idiopathic constipation; SBM= spontaneous bowel movement. *SBM response criteria: ‡3 observed SBMs/week and an increase from baseline of ‡1 SBM/week. Table 2. Lubiprostone Responder Rates for Improvement in CIC Symptoms in Patients in 3 Clinical Trials
S-534
Page 534