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P Ruegg - One of the best experts on this subject based on the ideXlab platform.
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a double blind placebo controlled randomized study to evaluate the efficacy safety and tolerability of Tegaserod in patients with irritable bowel syndrome
Scandinavian Journal of Gastroenterology, 2004Co-Authors: Henry Nyhlin, J Jones, P Ruegg, C Bang, L Elsborg, J Silvennoinen, I Holme, A WagnerAbstract:Background: Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western and Asia‐Pacific populations. This study evaluated the efficacy, safety and tolerability of Tegaserod versus placebo in patients with IBS. Methods: Patients with IBS (excluding those whose primary bowel symptom was diarrhoea) were randomized to receive either Tegaserod 6 mg b.i.d. (n = 327) or placebo (n = 320) for a 12‐week double‐blind treatment period. The primary efficacy variable (over weeks 1 to 4) was the response to the question: ‘Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?’ Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and the individual IBS symptoms. Results: Overall satisfactory relief was greater in the Tegaserod group than in the placebo group. Over weeks 1 to 4, the odds ratio was 1.54, that is, the odds of satisfactory relief were 54% higher in the Tegaserod group than in ...
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a randomized double blind placebo controlled trial of Tegaserod in female patients suffering from irritable bowel syndrome with constipation
Alimentary Pharmacology & Therapeutics, 2002Co-Authors: J Novick, P Ruegg, P Miner, R Krause, K Glebas, Harald Bliesath, G Ligozio, Martin LefkowitzAbstract:Summary Background : Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females. Aim : To evaluate the efficacy and safety of Tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation. Methods : In a randomized, double-blind, multicentre study, 1519 women received either Tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline period without treatment and followed by a 4-week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating. Results : Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, Tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of Tegaserod-treated patients. Conclusions : Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.
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Tegaserod a 5 ht4 receptor partial agonist relieves symptoms in irritable bowel syndrome patients with abdominal pain bloating and constipation
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: S Mullerlissner, E Pecher, Brigitte Nault, I Fumagalli, K D Bardhan, F Pace, P RueggAbstract:Aim: To investigate the efficacy and safety of Tegaserod, a novel 5-HT4 receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study. Methods: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received Tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks. Results: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of Tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with Tegaserod than placebo. Conclusions: Based upon the results of this study, Tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.
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Tegaserod a 5 ht 4 receptor partial agonist relieves symptoms in irritable bowel syndrome patients with abdominal pain bloating and constipation
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: S A Mullerlissner, E Pecher, Brigitte Nault, I Fumagalli, K D Bardhan, F Pace, P RueggAbstract:Aim: To investigate the efficacy and safety of Tegaserod, a novel 5-HT4 receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study. Methods: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received Tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks. Results: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of Tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with Tegaserod than placebo. Conclusions: Based upon the results of this study, Tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.
William D Chey - One of the best experts on this subject based on the ideXlab platform.
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re evaluation of the cardiovascular safety profile of Tegaserod a review of the clinical data
Clinical Gastroenterology and Hepatology, 2021Co-Authors: Brian E Lacy, Darren M Brenner, William D CheyAbstract:Background and Aims Tegaserod is a 5-HT4 receptor agonist approved for irritable bowel syndrome with constipation in women Methods An independent committee conducted an external adjudication to evaluate 24 possible cardiovascular ischemic events (Tegaserod: n = 20; placebo: n = 4) identified internally. A second independent external adjudication further evaluated these events. Results A total of 18,645 patients were included (Tegaserod: n = 11,614; placebo: n = 7031). The first adjudication identified 14 (0.075%) events (Tegaserod: n = 13 [0.11%]; placebo: n = 1 [0.014%]). All patients had ≥1 cardiovascular risk factor, and 11 had ≥2. The second adjudication identified 390 events, 24 (0.13%) were classified as probable new or worsening events (Tegaserod: 18 [0.16%]; placebo: 6 [0.09%]). For Tegaserod, 7 (0.06%) were coronary or cerebrovascular ischemic events compared with 1 (0.01%) for placebo (odds ratio, 4.24; 95% confidence interval, 0.52–34.74; P = .273). All Tegaserod patients reporting cardiovascular events had ≥1 risk, including cardiovascular disease, hyperlipidemia, ≥55 years of age, hypertension, diabetes, obesity, and smoking. Women Conclusions Two independent, external adjudications suggest that Tegaserod is safe for women
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Tegaserod for irritable bowel syndrome with constipation in women younger than 65 years without cardiovascular disease pooled analyses of 4 controlled trials
The American Journal of Gastroenterology, 2021Co-Authors: Eric D Shah, Brian E Lacy, William D Chey, Lin Chang, Darren M BrennerAbstract:INTRODUCTION Tegaserod was the first US Food and Drug Administration-approved drug for irritable bowel syndrome with constipation (IBS-C) in women and was recently reapproved for use. Recognizing that clinical trials were performed almost 20 years ago, we performed an integrated analysis on patient-reported outcomes relevant to current practice including previously unpublished data. METHODS Data from 4 12-week, randomized, placebo-controlled trials evaluating Tegaserod 6 mg b.i.d. in patients with IBS-C were pooled. We analyzed 2 groups: all women (overall population) and women younger than 65 years without a history of cardiovascular ischemic events (indicated population). The primary end point was subjective global assessment of IBS-C symptom relief. Responders rated themselves as "considerably" or "completely" relieved ≥50% of the time or at least "somewhat relieved" 100% of the time over the last 4 weeks. RESULTS The overall and indicated populations included 2,939 (Tegaserod [n = 1,478]; placebo [n = 1,461]) and 2,752 (Tegaserod [n = 1,386]; placebo [n = 1,366]) participants, respectively. The pooled odds ratios (95% confidence interval) for clinical response during the last 4 weeks in the overall and indicated populations with Tegaserod were 1.37 (1.18, 1.59; P < 0.001) and 1.38 (1.18, 1.61; P < 0.001). In the overall and indicated populations, clinical response rates for Tegaserod during the last 4 weeks were 43.3% and 44.1% versus 35.9% and 36.5% with placebo (P < 0.001). Adverse events were similar between groups. No significant cardiovascular events related to Tegaserod were observed in patients with ≤1 cardiac risk factor. DISCUSSION Tegaserod 6 mg b.i.d. reduced IBS-C symptoms in overall and US Food and Drug Administration-indicated populations (women aged <65 years with no history of cardiovascular ischemic events).
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long term Tegaserod treatment for dysmotility like functional dyspepsia results of two identical 1 year cohort studies
Digestive Diseases and Sciences, 2010Co-Authors: William D Chey, Jan Tack, G Ligozio, Colin W. Howden, David L. EarnestAbstract:Functional dyspepsia (FD) is a chronic disorder that adversely affects health-related quality of life (HRQoL). Published information on its long-term management is minimal and treatment options are limited. The aim of this study was to evaluate safety, efficacy and HRQoL with Tegaserod 6 mg twice daily over 1 year in women with FD who completed one of two 6-week, randomized, placebo-controlled, double-blind studies. About 780 patients received Tegaserod 6 mg twice daily in two identical 1-year extension studies. Scheduled assessments included adverse events, the Short-Form Nepean Dyspepsia Index (SF-NDI), Work Productivity and Activity Impairment-Dyspepsia (WPAI-Dyspepsia) questionnaire, and patient perceptions of treatment efficacy. Mean Tegaserod treatment duration in the two studies was 236 and 222 days. Most adverse events occurred in the first 6 months, were similar to previous reports (commonly diarrhea), and were transient and well tolerated. SF-NDI, WPAI-Dyspepsia scores and perceived symptom relief improved from baseline over the 1-year evaluation. The long-term safety profile of Tegaserod in women with FD was consistent with that of short-term treatment and accompanied by improvements in HRQoL, work productivity and symptom relief. These long-term results add to the clinical experience with FD and support the potential value of a 5-HT4 agonist in the management of FD.
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Tegaserod for female patients suffering from ibs with mixed bowel habits or constipation a randomized controlled trial
The American Journal of Gastroenterology, 2008Co-Authors: William D Chey, G Ligozio, Pierre Pare, Andrea Viegas, Michael ShetzlineAbstract:RESULTS: In total, 661 women were randomized (IBS-Mixed 324, IBS-C 337). Baseline symptom assessments identified clear differences between the two cohorts. Tegaserod provided significant improvement in satisfactory relief of IBS symptoms over 4 wk (OR 1.75, 95% CI 1.35‐2.25, P < 0.001) in both IBS-Mixed and IBS-C patients. Using the 75% rule, 52.3% of Tegaserod-receiving IBS-M patients and 43.3% of IBS-C patients were responders (vs 36.3, OR 1.88, 95% CI 1.16‐3.04, P < 0.010; and 28.9, OR 1.90, 95% CI 1.19‐3.05, P < 0.008 for placebo, respectively). The most frequent adverse events leading to study discontinuation in Tegaserod-treated patients were diarrhea (1.5%) and abdominal pain (0.9%). Overall 7% of IBS-C patients reported diarrhea compared to 12% of IBS-Mixed (placebo 2.4%, 1.8%, respectively). CONCLUSIONS: Tegaserod is effective in treating overall IBS symptoms in patients with IBS-Mixed and IBS-C. (Am J Gastroenterol 2008;103:1217‐1225)
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original contributions stomach Tegaserod treatment for dysmotility like functional dyspepsia results of two randomized controlled trials
2008Co-Authors: Nimish Vakil, Jeffrey Kralstein, David L. Earnest, William D Chey, Jan Tack, Nicholas J Talley, G Ligozio, Loren Laine, Salam Zakko, M CohardradiceAbstract:OBJECTIVES: Therapies for dysmotility-like functional dyspepsia (FD) are limited. We studied Tegaserod, a selective serotonin type 4 receptor agonist, in patients with FD. METHODS: Two identical multicenter, double-blind, randomized, placebo-controlled trials enrolled women ≥18 yr with recurring mid-upper abdominal discomfort characterized by postprandial fullness, early satiety, and/or bloating. Patients were randomized to Tegaserod 6 mg b.i.d. or placebo. Two patient-reported primary variables were assessed: percentage of days with satisfactory symptom relief, and symptom severity using the composite average daily severity score (CADSS). RESULTS: In total, 2,667 women were randomized with no differences between trials in terms of recruitment method, Helicobacter pylori status, heartburn, or medication use. Mean percentage of days with satisfactory symptom relief for Tegaserod versus placebo in Trial 1: 32.2% versus 26.6% (95% CI of treatment difference 2.82, 9.27; P < 0.01), Trial 2: 31.9% versus 29.4% (95% CI of treatment difference −0.21, 6.53; P = 0.066). Mean CADSS in Trial 1: 3.14 versus 3.35 (95% CI of treatment difference −0.29, −0.10; P < 0.0001), Trial 2: 3.15 versus 3.23 (95% CI of treatment difference −0.18, 0.01; P = 0.094). Meta-analysis showed significant benefit for both end points: increase in days with satisfactory relief 4.6% (95% CI 2.29, 6.96); decrease in CADSS 0.14 (95% CI 0.21, 0.07). Treatment effect was greater in patients with severe baseline symptoms. Diarrhea requiring study discontinuation was more common with Tegaserod than placebo (4.1% vs 0.3%). CONCLUSIONS: Some improvement in dysmotility-like FD was observed with Tegaserod treatment. The clinical implication of this improvement is uncertain. (Am J Gastroenterol 2008;103:1906‐1919)
Jan Tack - One of the best experts on this subject based on the ideXlab platform.
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influence of Tegaserod on proximal gastric tone and on the perception of gastric distention in functional dyspepsia
Neurogastroenterology and Motility, 2011Co-Authors: Jan Tack, Pieter Janssen, Raf Bisschops, Rita Vos, T Phillips, Gervais TougasAbstract:Background Abnormalities in gastric sensorimotor function (hypersensitivity to distention and impaired meal accommodation) have been implicated in the pathophysiology of functional dyspepsia (FD). To study the effect of the 5-HT4 agonist Tegaserod on sensitivity to gastric distention and gastric accommodation in FD. Methods Thirty FD patients (7 males, mean age 42 ± 2 years) underwent a gastric barostat study on two separate occasions, 2 weeks apart, after 5 days of pretreatment with placebo or Tegaserod 6 mg b.i.d. in a double-blind randomized order. After introduction of the barostat bag, graded isobaric distentions (2 mmHg increments/2 min) were performed to determine gastric compliance and sensitivity to distention. Subsequently, the pressure level was set at intra-abdominal pressure [minimal distending pressure (MDP)] + 2 mmHg for 90 min, with administration of a liquid meal (200 mL; 300 kcal) after 30 min. Key Results Tegaserod had no influence on MDP (7.9 ± 0.4 vs 7.4 ± 0.4 mmHg) or fasting gastric compliance (44 ± 10 vs 61 ± 6 mL mmHg−1) and on fasting thresholds for first perception (3.6 ± 0.4 vs 4.2 ± 0.2 mmHg above MDP) or discomfort (9.9 ± 0.7 vs 10.5 ± 0.5 mmHg above MDP). Tegaserod did not alter intra-balloon volumes before and after the meal [respectively 146 ± 14 vs 120 ± 11 and 297 ± 28 vs 283 ± 29 mL, not significant (NS)], or the amplitude of the meal-induced gastric relaxation (151 ± 23 vs 162 ± 23 mL, NS). In the subgroup with normal gastric emptying (n = 22), Tegaserod significantly enhanced meal-induced accommodation (126 ± 23 vs 175 ± 29 mL, anovaP < 0.001). Conclusions & Inferences Tegaserod does not alter gastric sensorimotor function in FD patients as a group. In the subgroup with normal gastric emptying, Tegaserod 6 mg b.i.d enhanced gastric accommodation.
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long term Tegaserod treatment for dysmotility like functional dyspepsia results of two identical 1 year cohort studies
Digestive Diseases and Sciences, 2010Co-Authors: William D Chey, Jan Tack, G Ligozio, Colin W. Howden, David L. EarnestAbstract:Functional dyspepsia (FD) is a chronic disorder that adversely affects health-related quality of life (HRQoL). Published information on its long-term management is minimal and treatment options are limited. The aim of this study was to evaluate safety, efficacy and HRQoL with Tegaserod 6 mg twice daily over 1 year in women with FD who completed one of two 6-week, randomized, placebo-controlled, double-blind studies. About 780 patients received Tegaserod 6 mg twice daily in two identical 1-year extension studies. Scheduled assessments included adverse events, the Short-Form Nepean Dyspepsia Index (SF-NDI), Work Productivity and Activity Impairment-Dyspepsia (WPAI-Dyspepsia) questionnaire, and patient perceptions of treatment efficacy. Mean Tegaserod treatment duration in the two studies was 236 and 222 days. Most adverse events occurred in the first 6 months, were similar to previous reports (commonly diarrhea), and were transient and well tolerated. SF-NDI, WPAI-Dyspepsia scores and perceived symptom relief improved from baseline over the 1-year evaluation. The long-term safety profile of Tegaserod in women with FD was consistent with that of short-term treatment and accompanied by improvements in HRQoL, work productivity and symptom relief. These long-term results add to the clinical experience with FD and support the potential value of a 5-HT4 agonist in the management of FD.
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original contributions stomach Tegaserod treatment for dysmotility like functional dyspepsia results of two randomized controlled trials
2008Co-Authors: Nimish Vakil, Jeffrey Kralstein, David L. Earnest, William D Chey, Jan Tack, Nicholas J Talley, G Ligozio, Loren Laine, Salam Zakko, M CohardradiceAbstract:OBJECTIVES: Therapies for dysmotility-like functional dyspepsia (FD) are limited. We studied Tegaserod, a selective serotonin type 4 receptor agonist, in patients with FD. METHODS: Two identical multicenter, double-blind, randomized, placebo-controlled trials enrolled women ≥18 yr with recurring mid-upper abdominal discomfort characterized by postprandial fullness, early satiety, and/or bloating. Patients were randomized to Tegaserod 6 mg b.i.d. or placebo. Two patient-reported primary variables were assessed: percentage of days with satisfactory symptom relief, and symptom severity using the composite average daily severity score (CADSS). RESULTS: In total, 2,667 women were randomized with no differences between trials in terms of recruitment method, Helicobacter pylori status, heartburn, or medication use. Mean percentage of days with satisfactory symptom relief for Tegaserod versus placebo in Trial 1: 32.2% versus 26.6% (95% CI of treatment difference 2.82, 9.27; P < 0.01), Trial 2: 31.9% versus 29.4% (95% CI of treatment difference −0.21, 6.53; P = 0.066). Mean CADSS in Trial 1: 3.14 versus 3.35 (95% CI of treatment difference −0.29, −0.10; P < 0.0001), Trial 2: 3.15 versus 3.23 (95% CI of treatment difference −0.18, 0.01; P = 0.094). Meta-analysis showed significant benefit for both end points: increase in days with satisfactory relief 4.6% (95% CI 2.29, 6.96); decrease in CADSS 0.14 (95% CI 0.21, 0.07). Treatment effect was greater in patients with severe baseline symptoms. Diarrhea requiring study discontinuation was more common with Tegaserod than placebo (4.1% vs 0.3%). CONCLUSIONS: Some improvement in dysmotility-like FD was observed with Tegaserod treatment. The clinical implication of this improvement is uncertain. (Am J Gastroenterol 2008;103:1906‐1919)
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a randomised controlled trial assessing the efficacy and safety of repeated Tegaserod therapy in women with irritable bowel syndrome with constipation
Gut, 2005Co-Authors: Jan Tack, S A Mullerlissner, Lin Chang, Peter Bytzer, Roberto Corinaldesi, A Viegas, S Schnekenbuehl, Cornelia Dungerbaldauf, Peter RueeggAbstract:Background: It has been proposed that treatments for irritable bowel syndrome with constipation (IBS-C) should provide rapid symptomatic relief, be intermittent, and effective upon repeated use. Aims: To evaluate the efficacy and safety of Tegaserod on IBS symptoms, and its impact on quality of life and health economic measures. Patients: Women (⩾18 years of age) with IBS-C according to the Rome II criteria. Methods: Prospective, double blind, placebo controlled, randomised trial. Women with IBS-C either received Tegaserod 6 mg twice daily or placebo for one month. Patients with at least a partial response entered a treatment free interval. Upon symptom recurrence, Tegaserod treated patients were re-randomised to Tegaserod or placebo for an additional month. Primary efficacy variables were response (overall IBS symptoms and abdominal discomfort/pain) to first and repeated treatment. Analysis was by intention to treat. Results: 2660 patients and 1191 patients were randomised for first and repeated treatment respectively. Tegaserod was superior to placebo for each primary efficacy variable (first treatment: 33.7% v 24.2% responders respectively for relief of IBS symptoms and 31.3% v 22.1% for relief of abdominal discomfort/pain; repeated treatment: 44.9% v 28.7%, and 42.4% v 27.1%, all p Conclusion: Tegaserod provides rapid and sustained relief of IBS-C symptoms both during first and repeated treatment.
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influence of Tegaserod on proximal gastric tone and on the perception of gastric distension
Alimentary Pharmacology & Therapeutics, 2003Co-Authors: Jan Tack, Robin Vos, Jozef Janssens, J Salter, S Jauffret, G VandeplasscheAbstract:Summary Background : Tegaserod, a 5-hydroxytryptamine-4 receptor agonist, enhances gastric emptying, but its effects on proximal stomach function have not been studied. Aim : To study the effect of Tegaserod on gastric compliance, accommodation and perception of distension in humans. Methods : Nineteen healthy volunteers (10 females; mean age, 23.9 years) were studied on three separate occasions after 7 days of treatment with placebo, Tegaserod 2 mg b.d. or Tegaserod 6 mg b.d. in a double-blind, randomized, three-way cross-over design. After the introduction of a barostat bag, stepwise distensions were performed to determine gastric compliance and sensitivity, and a mixed liquid meal was administered in isobaric mode to assess accommodation. Results : Tegaserod had no effect on the pressures or volumes inducing first perception or discomfort. Tegaserod 6 mg b.d. enhanced fasting gastric compliance compared with placebo. Pre-prandial and post-prandial intra-balloon volumes were significantly higher after 6 mg b.d. than after placebo. Both Tegaserod 2 and 6 mg b.d. shortened the time to maximum post-prandial intra-balloon volume. The amplitude of meal-induced gastric relaxation (post-prandial minus pre-prandial volumes) did not differ between the treatment arms. Conclusion : In humans, Tegaserod allows for larger intra-balloon volumes both before and after a meal. These findings warrant the investigation of the therapeutic potential of Tegaserod in dyspeptic patients with impaired accommodation.
David L. Earnest - One of the best experts on this subject based on the ideXlab platform.
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the zelnorm epidemiologic study zest a cohort study evaluating incidence of abdominal and pelvic surgery related to Tegaserod treatment
BMC Gastroenterology, 2012Co-Authors: John D Seeger, Sherry Quinn, Elena Rivero, David L. Earnest, Anthony Lembo, Alexander M WalkerAbstract:Background Pre-marketing clinical studies of Tegaserod suggested an increased risk of abdominal surgery, particularly cholecystectomy. We sought to quantify the association between Tegaserod use and the occurrence of abdominal or pelvic surgery, including cholecystectomy.
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Tegaserod and the risk of cardiovascular ischemic events: an observational cohort study.
Journal of Cardiovascular Pharmacology and Therapeutics, 2010Co-Authors: Jeanne Loughlin, Sherry Quinn, Elena Rivero, Judy Wong, Jiaquing Huang, Jeffrey Kralstein, David L. Earnest, John D SeegerAbstract:Objectives: Tegaserod, a partial 5-HT4 agonist previously approved for treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation, was suspended from US marketing in 2007, based on pooled clinical trial results which contained a signal suggesting increased risk of cardiovascular ischemic events (CVIEs). We sought to evaluate whether there was an association between Tegaserod and CVIE in a setting of routine clinical practice. Methods: This was a matched cohort study conducted within a large US health insurance database, involving 52 229 patients who initiated Tegaserod and 52 229 patients with similar characteristics who did not initiate Tegaserod. Participants were followed for up to 6 months for the occurrence of CVIE (myocardial infarction, acute coronary syndrome, coronary revascularization, and stroke). Outcomes were identified using insurance claims and were confirmed by review of medical records. We conducted as-matched analyses providing hazard ratios (HRs) along w...
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long term Tegaserod treatment for dysmotility like functional dyspepsia results of two identical 1 year cohort studies
Digestive Diseases and Sciences, 2010Co-Authors: William D Chey, Jan Tack, G Ligozio, Colin W. Howden, David L. EarnestAbstract:Functional dyspepsia (FD) is a chronic disorder that adversely affects health-related quality of life (HRQoL). Published information on its long-term management is minimal and treatment options are limited. The aim of this study was to evaluate safety, efficacy and HRQoL with Tegaserod 6 mg twice daily over 1 year in women with FD who completed one of two 6-week, randomized, placebo-controlled, double-blind studies. About 780 patients received Tegaserod 6 mg twice daily in two identical 1-year extension studies. Scheduled assessments included adverse events, the Short-Form Nepean Dyspepsia Index (SF-NDI), Work Productivity and Activity Impairment-Dyspepsia (WPAI-Dyspepsia) questionnaire, and patient perceptions of treatment efficacy. Mean Tegaserod treatment duration in the two studies was 236 and 222 days. Most adverse events occurred in the first 6 months, were similar to previous reports (commonly diarrhea), and were transient and well tolerated. SF-NDI, WPAI-Dyspepsia scores and perceived symptom relief improved from baseline over the 1-year evaluation. The long-term safety profile of Tegaserod in women with FD was consistent with that of short-term treatment and accompanied by improvements in HRQoL, work productivity and symptom relief. These long-term results add to the clinical experience with FD and support the potential value of a 5-HT4 agonist in the management of FD.
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original contributions stomach Tegaserod treatment for dysmotility like functional dyspepsia results of two randomized controlled trials
2008Co-Authors: Nimish Vakil, Jeffrey Kralstein, David L. Earnest, William D Chey, Jan Tack, Nicholas J Talley, G Ligozio, Loren Laine, Salam Zakko, M CohardradiceAbstract:OBJECTIVES: Therapies for dysmotility-like functional dyspepsia (FD) are limited. We studied Tegaserod, a selective serotonin type 4 receptor agonist, in patients with FD. METHODS: Two identical multicenter, double-blind, randomized, placebo-controlled trials enrolled women ≥18 yr with recurring mid-upper abdominal discomfort characterized by postprandial fullness, early satiety, and/or bloating. Patients were randomized to Tegaserod 6 mg b.i.d. or placebo. Two patient-reported primary variables were assessed: percentage of days with satisfactory symptom relief, and symptom severity using the composite average daily severity score (CADSS). RESULTS: In total, 2,667 women were randomized with no differences between trials in terms of recruitment method, Helicobacter pylori status, heartburn, or medication use. Mean percentage of days with satisfactory symptom relief for Tegaserod versus placebo in Trial 1: 32.2% versus 26.6% (95% CI of treatment difference 2.82, 9.27; P < 0.01), Trial 2: 31.9% versus 29.4% (95% CI of treatment difference −0.21, 6.53; P = 0.066). Mean CADSS in Trial 1: 3.14 versus 3.35 (95% CI of treatment difference −0.29, −0.10; P < 0.0001), Trial 2: 3.15 versus 3.23 (95% CI of treatment difference −0.18, 0.01; P = 0.094). Meta-analysis showed significant benefit for both end points: increase in days with satisfactory relief 4.6% (95% CI 2.29, 6.96); decrease in CADSS 0.14 (95% CI 0.21, 0.07). Treatment effect was greater in patients with severe baseline symptoms. Diarrhea requiring study discontinuation was more common with Tegaserod than placebo (4.1% vs 0.3%). CONCLUSIONS: Some improvement in dysmotility-like FD was observed with Tegaserod treatment. The clinical implication of this improvement is uncertain. (Am J Gastroenterol 2008;103:1906‐1919)
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double blind randomized placebo controlled study to evaluate the effects of Tegaserod on gastric motor sensory and myoelectric function in healthy volunteers
Alimentary Pharmacology & Therapeutics, 2006Co-Authors: Nicholas J Talley, Michael Camilleri, Alan R Zinsmeister, G Thomforde, D Burton, Kenneth L Koch, M J Rucker, J Peterson, David L. EarnestAbstract:Summary Background The effects of Tegaserod on gastric accommodation and postprandial satiety remain unclear. Aim To compare the effects of Tegaserod 6 mg twice daily vs. placebo on gastric volumes, postprandial symptoms, gastric emptying, small bowel transit and the surface electrogastrogram in female and male healthy volunteers. Methods Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of Tegaserod 6 mg twice daily (n = 21) vs. placebo (n = 20) in healthy volunteers. Validated methods were used to study gastric emptying, myoelectrical activity, volumes and satiation postnutrient challenge. Results There were no significant effects of Tegaserod on the primary endpoints assessing gastric function: emptying of solids or liquids, total gastric volumes or myoelectrical activity. Maximum tolerated volume and aggregate symptom score with nutrient challenge on placebo were 1035 mL (±44) and 130 (±15) vs. 989 mL (±43) and 117 (±15) during Tegaserod, respectively (all P = N.S.). Postprandial change in proximal gastric volume by single photon emission-computed tomography was decreased in females on Tegaserod (246 ± 30) vs. placebo (358 ± 32) (P = 0.015). Proximal fasting volumes in females were increased on Tegaserod (126 ± 12) vs. placebo (92 ± 13) (P = 0.066). Conclusions While Tegaserod decreased proximal gastric volume change after a meal, it does not appear to have significant effects on gastric motor and sensory function in healthy individuals. Further studies are required in patients with disturbances of gastric motor and sensory function.
Brigitte Nault - One of the best experts on this subject based on the ideXlab platform.
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effect of Tegaserod in chronic constipation a randomized double blind controlled trial
Clinical Gastroenterology and Hepatology, 2004Co-Authors: John F. Johanson, William D Chey, Arnold Wald, Gervais Tougas, J Novick, Anthony Lembo, Fiona Fordham, Mary Guella, Brigitte NaultAbstract:Background & Aims: Chronic constipation is a common gastrointestinal disorder. The aim of this study was to evaluate the efficacy, safety, and tolerability of Tegaserod, a serotonin subtype 4 receptor partial agonist in patients with chronic constipation. Methods: This was a randomized, double-blind, placebo-controlled study. After a 2-week baseline, patients received Tegaserod 2 mg twice daily (n = 450), Tegaserod 6 mg twice daily (n = 451), or placebo (n = 447) for 12 weeks, followed by a 4-week withdrawal period. Responders were those patients having been treated for at least 7 days with an increase of ≥1 complete spontaneous bowel movement/week vs. baseline during weeks 1–4 (primary variable) and weeks 1–12 (secondary variable). Other secondary variables included patient assessment of constipation symptoms (number of bowel movements, stool form, abdominal bloating/distention, straining, and abdominal pain/discomfort), and global assessment of constipation and bowel habits. Results: Responder rates for complete spontaneous bowel movement during weeks 1–4 were significantly greater ( P
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long term safety of Tegaserod in patients with constipation predominant irritable bowel syndrome
Alimentary Pharmacology & Therapeutics, 2002Co-Authors: Gervais Tougas, David L. Earnest, W J Snape, M H Otten, K E Langaker, R E Pruitt, E Pecher, Brigitte Nault, Mikhail RojavinAbstract:Summary Background : Tegaserod is a 5-hydroxytryptamine-4 receptor partial agonist. Oral administration causes gastrointestinal effects resulting in increased gastrointestinal motility and attenuation of visceral sensation. Aim : To determine the long-term safety and tolerability of Tegaserod in patients suffering from irritable bowel syndrome with constipation as the predominant symptom of altered bowel habits. Method : A multicentre, open-label study with flexible dose titration of Tegaserod in out-patients suffering from constipation-predominant irritable bowel syndrome. Results : A total of 579 patients with constipation-predominant irritable bowel syndrome were treated with Tegaserod. Of these, 304 (53%) completed the trial. The most common adverse events, classified as related to Tegaserod for any dose, were mild and transient diarrhoea (10.1%), headache (8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious adverse events were reported in 25 patients (4.4% of patients) leading to discontinuation in six patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to Tegaserod. There were no consistent differences in adverse events between patients previously exposed to Tegaserod and those treated de novo. No pattern-forming Tegaserod-related abnormalities in haematological and biochemical laboratory tests, urinalysis, blood pressure, pulse rate or electrocardiograms were found. Conclusions : Tegaserod appears to be well tolerated in the treatment of patients with constipation-predominant irritable bowel syndrome. The adverse event profile, clinical laboratory evaluations, vital signs and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12-month period.
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Tegaserod a 5 ht4 receptor partial agonist relieves symptoms in irritable bowel syndrome patients with abdominal pain bloating and constipation
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: S Mullerlissner, E Pecher, Brigitte Nault, I Fumagalli, K D Bardhan, F Pace, P RueggAbstract:Aim: To investigate the efficacy and safety of Tegaserod, a novel 5-HT4 receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study. Methods: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received Tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks. Results: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of Tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with Tegaserod than placebo. Conclusions: Based upon the results of this study, Tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.
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Tegaserod a 5 ht 4 receptor partial agonist relieves symptoms in irritable bowel syndrome patients with abdominal pain bloating and constipation
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: S A Mullerlissner, E Pecher, Brigitte Nault, I Fumagalli, K D Bardhan, F Pace, P RueggAbstract:Aim: To investigate the efficacy and safety of Tegaserod, a novel 5-HT4 receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study. Methods: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received Tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks. Results: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of Tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with Tegaserod than placebo. Conclusions: Based upon the results of this study, Tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.
