John F. Johanson

Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome – results of two randomized, placebo-controlled studies

Backgroundu2002 Effective treatments for irritable bowel syndrome with constipation (IBS‐C) are lacking.

Multicenter, 4-Week, Double-Blind, Randomized, Placebo-Controlled Trial of Lubiprostone, a Locally-Acting Type-2 Chloride Channel Activator, in Patients With Chronic Constipation

OBJECTIVES:To assess the efficacy and safety of lubiprostone in adults with chronic constipation.METHODS:This multicenter, parallel-group, double-blind controlled trial enrolled 242 patients with constipation and randomized them to receive oral lubiprostone 24 mcg or placebo twice daily for 4 wk. The primary efficacy end point was the number of spontaneous bowel movements (SBMs; those occurring without use of constipation relieving medications) after 1 wk of double-blind treatment. Other evaluations included SBMs at weeks 2, 3, and 4; bowel movement (BM) characteristics (i.e., consistency and straining); constipation severity; abdominal bloating/discomfort; global treatment effectiveness ratings; and safety assessments.RESULTS:The 120 lubiprostone-treated patients reported a greater mean number of SBMs at week 1 compared with the 122 placebo-treated patients (5.69 vs 3.46, P = 0.0001), with a greater frequency of SBMs also reported at weeks 2, 3, and 4 (P ≤ 0.002). Within 24 h of the first dose of study drug, 56.7% of those given lubiprostone reported a SBM compared with 36.9% of those given placebo (P = 0.0024); within 48 h, 80% and 60.7% of these patients reported a SBM (P = 0.0013), respectively. Stool consistency, straining, and constipation severity, as well as patient-reported assessments of treatment effectiveness, were significantly improved with lubiprostone compared with placebo at all weeks (P ≤ 0.0003). The two most common treatment-related adverse events were nausea (31.7%) and headache (11.7%).CONCLUSIONS:In patients with chronic constipation, treatment with lubiprostone produces a BM in the majority of individuals within 24–48 h of initial dosing and improves the frequency as well as other characteristics associated with BMs with short-term (i.e., 4 wk) treatment. The most commonly reported adverse event was mild to moderate nausea, which resulted in treatment discontinuation in 5% of treated patients.

Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation

Backgroundu2002 Analyses of a trial in constipated patients indicated that lubiprostone may be an effective treatment for irritable bowel syndrome with constipation.

Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial.

BACKGROUND AND AIMSnChronic 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.nnnMETHODSnThis 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 > or =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.nnnRESULTSnResponder rates for complete spontaneous bowel movement during weeks 1-4 were significantly greater ( P < 0.0001) in the tegaserod 2 mg twice daily (41.4%) and 6 mg twice daily groups (43.2%) vs. placebo (25.1%). This effect was maintained over 12 weeks. Statistically significant improvements over placebo were observed across the majority of secondary variables for both tegaserod doses. No rebound effect was observed after treatment withdrawal. Tegaserod was well tolerated; headache and nasopharyngitis, the most frequent adverse events, were more common in the placebo group than in either tegaserod group.nnnCONCLUSIONSnOver 12 weeks, tegaserod treatment produced significant improvements in chronic constipation symptoms and was also safe and well tolerated.

Efficacy and Safety of Lubiprostone in Patients with Chronic Constipation

AimsThe aim of this study is to assess the efficacy and safety of lubiprostone in adults with chronic constipation.MethodsThis multicenter, parallel-group trial enrolled 237 patients with chronic constipation and randomized them to 4xa0weeks of double-blind treatment with oral lubiprostone 24xa0mcg or placebo twice daily. The primary efficacy endpoint was the number of spontaneous bowel movements (SBMs) after 1xa0week of treatment. Secondary evaluations included SBMs at weeksxa02, 3, and 4; percentage of patients with a SBM within 24xa0h of first study dose; stool consistency; degree of straining; constipation severity; abdominal bloating and discomfort; global treatment effectiveness; and safety assessments.ResultsLubiprostone-treated patients experienced greater mean numbers of SBMs at weekxa01 compared with placebo (5.89 versus 3.99, Pxa0=xa00.0001), with significantly greater percentages having SBMs within 24xa0h of the first dose (61.3% versus 31.4%, Pxa0<xa00.0001). At each assessment, SBM frequency and percentages of full responders (≥4 SBM per week) were significantly greater among lubiprostone-treated patients compared with placebo (Pxa0≤xa00.0171). Lubiprostone-treated patients reported significant improvements in stool consistency, straining, and constipation severity at all weeks, and in abdominal bloating at weekxa01. Patient assessments of treatment effectiveness were significantly greater with lubiprostone compared with placebo at all weeks (Pxa0<xa00.0004). Gastrointestinal-related disorders were the most common adverse events in both treatment groups.ConclusionsIn patients with chronic constipation, lubiprostone produced a bowel movement in the majority of individuals within 24xa0h of initial dosing, with sustained improvement in frequency as well as other constipation symptoms over 4xa0weeks of treatment.

Meta-analysis of flavonoids for the treatment of haemorrhoids†

The aim of the study was to evaluate the impact of flavonoids on those symptoms important to patients with symptomatic haemorrhoids.

Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation

Irritable bowel syndrome with constipation (IBS‐C) significantly decreases quality of life and the ability to perform daily living activities.

Clinical trial: the efficacy and tolerability of velusetrag, a selective 5‐HT4 agonist with high intrinsic activity, in chronic idiopathic constipation – a 4‐week, randomized, double‐blind, placebo‐controlled, dose–response study

Aliment Pharmacol Ther 2010; 32: 1102–1112

A Randomized, Multicenter Study Comparing the Safety and Efficacy of Sodium Phosphate Tablets With 2L Polyethylene Glycol Solution Plus Bisacodyl Tablets for Colon Cleansing

OBJECTIVE:The safety and efficacy of NaP tablets have not been compared with 2L PEG lavage solution. A multicenter, investigator-blinded study was conducted to compare the colon-cleansing efficacy of a new NaP tablet formulation with that of 2L PEG solution plus bisacodyl tablets in adults undergoing colonoscopy.METHODS:A total of 481 patients were randomized to receive either 32 tablets (48 g) of NaP or 2L PEG solution plus 4 (20 mg) bisacodyl tablets. Quality of colon cleansing was assessed using a 4-point scale (1 = excellent, 2 = good, 3 = fair, and 4 = inadequate), and the primary efficacy end point was mean overall colon-cleansing score. Safety assessments included recording of adverse events and changes in biochemical tests and vital signs.RESULTS:A total of 411 patients were included in the efficacy analysis. The mean overall and ascending colon-cleansing scores for NaP tablets were significantly better than PEG plus bisacodyl (overall 1.5 vs 1.8, ascending 1.4 vs 1.8, P < 0.0001 for both). Patients treated with NaP tablets experienced significantly fewer adverse events (66% vs 82%, P = 0.0003) and gastrointestinal symptoms (64% vs 79%, P = 0.0001) compared with patients receiving PEG plus bisacodyl. Patients receiving NaP tablets were significantly less likely to experience abdominal distention, abdominal pain, and vomiting than patients receiving PEG plus bisacodyl (P < 0.0012). Transient fluctuations in laboratory parameters were observed in both treatment groups; however, the fluctuations were more common and of greater magnitude in the NaP group particularly in phosphorous, sodium, and potassium.CONCLUSION:The colon-cleansing efficacy of the new 32-tablet NaP dosing regimen in this study was found to be significantly better than the 2L PEG solution plus bisacodyl tablets regimen. The 32-tablet NaP dosing regimen was associated with fewer adverse events. As expected electrolyte shifts were more common and of greater magnitude in the NaP group compared with the PEG plus bisacodyl group; however, both treatment groups demonstrated significant changes in electrolytes and creatinine.

Long-Term Safety and Effectiveness of Lubiprostone, a Chloride Channel (ClC-2) Activator, in Patients with Chronic Idiopathic Constipation

BackgroundLubiprostone helps relieve constipation in short-term 4-week studies. There are limited data on long-term pharmacological treatment with lubiprostone for chronic idiopathic constipation.AimsTo examine the long-term safety and effectiveness of lubiprostone in patients with chronic idiopathic constipation.MethodsIn this prospective, multicenter, open-labeled trial, 248 patients agedxa0≥18xa0years with chronic idiopathic constipation were directed to take lubiprostone 24 mcg BID as needed for 48xa0weeks. Patients were allowed to decrease the dose in response to the perceived severity of constipation and need for relief. Hematology and chemistry profiles and assessment of constipation symptoms and its severity were performed at all visits. Adverse events (AEs) were recorded.ResultsOf the 248 patients who entered the trial, 127 (51%) completed the trial. A dose reduction was observed in 17% of the patients, resulting in an average study medication exposure across the study of approximately 1.7 capsules (or approximately 40.8 mcg) per day. The most common treatment-related AEs were nausea (19.8%), diarrhea (9.7%), abdominal distension (6.9%), headache (6.9%), and abdominal pain (5.2%). No deaths were reported and of the 16 reported serious AEs, one was considered possibly treatment related. Average changes in serum electrolytes were not clinically relevant at any time point during the study. On average, lubiprostone significantly (pxa0<xa00.0001) reduced patient-reported constipation severity, abdominal bloating, and abdominal discomfort across 48xa0weeks when compared to baseline.ConclusionsDuring this 48-week open-label study, lubiprostone was well tolerated. Bowel symptoms consistently improved over 48xa0weeks in adult patients with chronic idiopathic constipation.