A randomized, double-blind, placebo-controlled study to assess efficacy and safety of 0.5 mg and 1 mg alosetron in women with severe diarrhea-predominant IBS.

OBJECTIVE: Alosetron is indicated for women with chronic, severe diarrhea-predominant IBS (d-IBS) who have not responded adequately to conventional therapy. Constipation is the most common adverse event with alosetron treatment. Multiple dosing regimens were assessed in a randomized, double-blind, placebo-controlled study (S3B30040) to determine efficacy, tolerability, and evaluate constipation rate. METHODS: 705 women with severe d-IBS were randomized to placebo, alosetron 0.5 mg once daily, 1 mg once daily, or 1 mg twice daily for 12 wk. The primary end point was the proportion of week 12 responders (patients with moderate or substantial improvement in IBS symptoms) on the 7-point Likert Global Improvement Scale (GIS). Secondary end points were average rate of adequate relief of IBS pain and discomfort, and bowel symptom improvements. RESULTS: The proportion of GIS responders at week 12 (primary time point) was significantly greater in all alosetron groups compared with placebo (54/176 [30.7%], 90/177 [50.8%], 84/175 [48%], and 76/177 [42.9%] for placebo, 0.5, 1 mg once daily, and 1 mg twice daily alosetron groups, respectively; P< or = 0.02). Results were similar for the average adequate relief rate (treatment effects > or =12%, P< or = 0.038). Bowel symptoms were improved in all alosetron groups. Constipation was the most common adverse event (9%, 16%, and 19% patients in the 0.5 mg, 1 mg once daily, and 1 mg twice daily groups, respectively). One event of intestinal obstruction and one of ischemic colitis occurred in the 0.5 mg group, and one event of fecal impaction occurred in the 1 mg twice-daily group. All were self-limited and resolved without sequelae. CONCLUSION: Alosetron 0.5 mg and 1 mg once daily as well as 1 mg twice daily are effective in providing global improvement in IBS symptoms, adequate relief of IBS pain and discomfort, and improvement in bowel symptoms in women with severe d-IBS. Lower dosing regimens resulted in a decreased constipation rate.

Ranitidine (Zantac) syrup versus Ranitidine effervescent tablets (Zantac) EFFERdose) in children: a single-center taste preference study.

BACKGROUND: The histamine H(2) receptor antagonist ranitidine is US FDA-approved for the treatment of gastroesophageal reflux disease and healing of erosive esophagitis in children >or=1 month of age. A low-dose strength of ranitidine is now available in a citrus-flavored 25 mg effervescent tablet (dissolved in 5 mL of water); this formulation was developed to facilitate use in infants and smaller children. Ranitidine syrup is available in a peppermint-flavored 15 mg/mL formulation. OBJECTIVE: To compare taste preferences for ranitidine (Zantac) syrup and ranitidine effervescent tablets dissolved in water (Zantac EFFERdose) in healthy children aged 4-8 years and their adult caregivers. STUDY DESIGN AND METHODS: A randomized, single-blind, crossover, taste test trial was conducted in 102 children and 102 parents/legal guardians. All subjects received a single 45 mg dose of each formulation. After tasting both preparations children were asked: "Now that you have tasted both medicines, which one of these medicines do you think tastes better?" Adults were asked four questions to assess whether they would administer the medication to the children. RESULTS: Seventy-one percent (72/102) of the children preferred the taste of the ranitidine effervescent tablets compared with 29% (30/102) who preferred the syrup (p < 0.001). The majority of adults (71%) responded that they would prefer to administer the effervescent formulation based on taste. Adverse events consistent with product labeling were mild and were reported in four children and three adults: headache (n = 3), drowsiness (n = 1), abdominal pain/cramps (n = 2), and bloating/gas (n = 1). CONCLUSION: The taste of the ranitidine effervescent formulation dissolved in water is preferred over the ranitidine syrup. Better taste acceptance may facilitate ease of administration and compliance in pediatric patients.

A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS.

BACKGROUND: A randomized, double blind, placebo-controlled dose-ranging study was conducted to assess the efficacy of alosetron in men with diarrhea-predominant irritable bowel syndrome (IBS). METHODS: Six hundred and sixty-two men were randomized to treatment with alosetron 0.5, 1.0, 2.0, 4.0 mg, or placebo twice daily for 12 wk, followed by a 4-wk posttreatment period. Adequate relief of IBS pain and discomfort during week 5-12 of the treatment phase was the primary endpoint; secondary endpoints included bowel urgency, stool frequency, and consistency, incomplete evacuation, bloating, and abdominal pain or discomfort. RESULTS: Subjects ranked urgency and abdominal pain as their most bothersome IBS symptoms. The average rate of adequate relief during week 5-12 was significantly higher in the alosetron 1.0 mg twice-daily group compared to placebo (53%vs 40%, p= 0.04), and all doses of alosetron significantly reduced stool consistency scores (p < 0.001) indicating firmer stools. No significant effects of alosetron were seen with regard to urgency, number of bowel movements, bloating, and incomplete evacuation. Constipation was the most common adverse event and occurred in a dose-related manner among subjects receiving alosetron, 9% (0.5 mg twice daily), 15% (1.0 mg twice daily), 11% (2.0 mg twice daily), and 21% (4.0 mg twice daily). No serious adverse events of constipation were reported. One subject in the 0.5 mg twice-daily group had an episode of rectal bleeding suggestive of a possible diagnosis of ischemic colitis. CONCLUSIONS: Alosetron 1 mg twice daily provided adequate relief of IBS pain and discomfort, and improved stool consistency in men with diarrhea-predominant IBS.

Long-term safety and efficacy of alosetron in women with severe diarrhea-predominant irritable bowel syndrome.

OBJECTIVES: To assess long-term safety and efficacy of alosetron in women with severe, chronic diarrhea-predominant IBS and in a subset having more frequent urgency (i.e., bowel urgency at least 10 of 14 days during screening). METHODS: Randomized patients received either alosetron 1 mg (n = 351) or placebo (n = 363) twice daily during a 48-wk, double-blind study. The primary endpoint was the 48-wk average rate of adequate relief of IBS pain and discomfort. Secondary endpoints included 48-wk average satisfactory control rates of urgency, stool frequency, stool consistency, and bloating. Other efficacy endpoints were average monthly adequate relief and urgency control rates and impact of provided rescue medication. RESULTS: Alosetron-treated patients had significantly greater 48-wk average adequate relief (p= 0.01) and urgency control (p < 0.001) rates, regardless of rescue medication use, compared with placebo. Results in subjects with more frequent urgency were more robust than those in the overall population (p= 0.005). In weeks without rescue medication use, satisfactory control rates for stool frequency and stool consistency were significantly greater in alosetron-treated patients than placebo. Alosetron-treated patients had significantly greater adequate relief than placebo-treated patients (p < 0.05) in 9 of 12 months and significantly greater urgency control (p < 0.001) in all months. Adequate relief and urgency control were maintained throughout the treatment. Adverse events and serious adverse events were similar between treatment groups, except for constipation. Neither ischemic colitis nor serious events related to bowel motor dysfunction was reported. CONCLUSIONS: Long-term use of alosetron is effective and well-tolerated in women with chronic, diarrhea-predominant IBS, including those with more frequent urgency.

Effect of alosetron on bowel urgency and global symptoms in women with severe, diarrhea-predominant irritable bowel syndrome: analysis of two controlled trials.

BACKGROUND & AIMS: The aim of this study was to assess the effect of alosetron on bowel urgency and irritable bowel syndrome (IBS) global improvement in diarrhea-predominant IBS (D-IBS). METHODS: Women with a lack of satisfactory bowel urgency control at least 50% of the time during screening were randomized to receive alosetron 1 mg (n = 246) or placebo (n = 246) twice daily. The primary end point was the percentage of days with satisfactory control of bowel urgency. The response rate for the IBS global improvement scale (GIS) was a secondary end point. GIS responders were patients who recorded either moderate or substantial improvement in IBS symptoms relative to the way they felt before entering the study. Other end points included improvement in stool frequency, stool consistency, and percentage of days with incomplete evacuation. Further analyses were performed on a subset of patients who had at least 10 of 14 days during screening (>/=71% of days) with a lack of satisfactory control of bowel urgency. RESULTS: Patients had severe chronic IBS symptoms, and 89% of patients had D-IBS. Alosetron resulted in a greater percentage of days with satisfactory control of urgency compared with placebo (69% vs. 56%, respectively, P < 0.001). Greater percentages of alosetron-treated patients were GIS responders at 4, 8, and 12 weeks compared with placebo (59% vs. 41%, 63% vs. 41%, and 68% vs. 46%, respectively, P < 0.001). Patients with more frequent urgency had similar results. Constipation occurred in 28% and 9% of subjects in the alosetron- and placebo-treated groups, respectively. No cases of ischemic colitis were reported. CONCLUSIONS: Alosetron effectively manages bowel urgency and improves global symptoms in women with severe chronic D-IBS.