Recurrent Diarrhea

February 16, 2016

Allergan issued results of a phase III study of VIBERZI C IV (eluxadoline) for the treatment of irritable bowel syndrome with diarrhea (IBS-D). The trial results are from two phase III randomized, multicenter, multi-national, double-blind, placebo-controlled trials (Studies 1 and 2). A total of 1280 patients in Study 1 and 1145 patients in Study 2 received treatment with VIBERZI 75mg, VIBERZI 100mg or placebo twice daily. Overall, the patients were a mean age of 45 years (ranging from 18 to 80 years with 10% at least 65 years of age or older), 66% female, 86% white, 11% black and 27% Hispanic. In these trials, significantly more patients treated with VIBERZI experienced improvements in diarrhea and abdominal pain, as compared with placebo. Efficacy was defined as simultaneous reductions in the daily worst abdominal pain score by >30% as compared to the baseline weekly average and a reduction in the Bristol Stool Scale (BSS) to <5, on at least 50% of the days within a 12-week treatment interval. These trial results demonstrated sustained and effective relief of both symptoms. Based on efficacy of VIBERZI 75mg and 100mg at 12 weeks of treatment, VIBERZI was approved by the FDA as a twice-daily, oral treatment indicated for use in adults suffering from IBS-D.

August 18, 2014

Salix Pharmaceuticals reported results of a phase III study of rifaximin for the treatment of irritable bowel syndrome with diarrhea (IBS-D). The phase III, randomized, double-blind, placebo- controlled study evaluated repeat treatment with rifaximin 550mg TID (three times daily) for 14 days in subjects with IBS-D, who respond to an initial treatment course with rifaximin 550mg TID for 14 days. Results indicate a significantly greater proportion of rifaximin-treated subjects, compared to placebo-treated subjects, gained relief in both IBS-related abdominal pain and stool consistency during the PEP in the first repeat double-blind, placebo-controlled treatment phase, and continued to respond without recurrence through the end of week six following the second repeat double-blind, placebo-controlled treatment (p=0.0068). Results also indicate, compared to placebo-treated subjects, a significantly greater proportion of rifaximin-treated subjects gained relief in both IBS-related abdominal pain and stool consistency during the PEP in the first repeat double-blind, placebo- controlled treatment phase and continued to respond without recurrence through the end of week 12, independent of any additional treatment (p=0.0419).

May 27, 2013

Intercept Pharmaceuticals released preliminary results from a phase IIa trial of obeticholic acid for primary bile acid diarrhea (PBAD). This open-label study, OBADIAH, enrolled 10 patients with PBAD, IBS-D or secondary bile acid diarrhea due to Crohn’s disease. Subjects received OCA 25mg daily for two weeks. Data demonstrated OCA 25mg resulted in a statistically significant increase in median fasting fibroblast growth factor 19 (FGF19) from 133pg/mL to 237pg/mL, with most patients achieving a >60% increase (p=0.007). In addition, clinical improvements were seen in all patients with reductions in median stool frequency from 23 to 14 per week (p=0.03) and an improvement in the median Bristol Stool Form Scale assessing stool type from 5.15 to 4.34 (p=0.05). Notably, during the two-week follow-up period after stopping OCA therapy, stool frequency returned to pre-treatment baseline values. OCA was well tolerated. Intercept Pharmaceuticals anticipates final results for all three patient groups to be available in the second half of 2013.

October 22, 2012

Lexicon Pharmaceuticals reported results from a phase II trial of telotristat etiprate in carcinoid syndrome. This open-label, dose-escalation study enrolled 15 patients with metastatic carcinoid syndrome who were refractory to or could not tolerate somatostatin analog therapy. Subjects received ascending doses of telotristat etiprate 150mg, 250mg, 350mg and 500mg, administered three times daily for 14 days on each dose until reaching a maximal dose, which was then continued until the completion of 12 weeks of therapy. Data showed subjects experienced a 46.4% median reduction from baseline at week 12, with the number of daily bowel movements steadily decreasing over time. All observed changes from baseline were statistically significant at p<0.001. At the completion of 12 weeks, 75% of subjects reported improvement. Subjects also saw statistically significant improvements in stool consistency (p<0.001), trends of reductions in abdominal pain (p=0.09) and the number of cutaneous flushing episodes (p=0.052). The median percentage reductions from baseline of urinary 5-HIAA at weeks 8 and 12 were 68.3% (p=0.019) and 72.7% (p=0.031), respectively. Telotristat etiprate was well tolerated. There was no evidence of dose-limiting toxicity. Based on these data, Lexicon is advancing telotristat etiprate to phase III trials.

September 17, 2012

Santarus reported results from a phase II trial of rifamycin SV MMX for the treatment of travelers’ diarrhea. This multinational, multi-center, randomized, double-blind, placebo-controlled study enrolled 264 patients. Subjects received rifamycin SV MMX 400mg twice daily or placebo for three days. Results showed that the trial met its primary endpoint of reducing time to last unformed stool (TLUS) in patients with travelers’ diarrhea. The primary endpoint was defined as the time (hours) between the administration of the first dose of study drug and the time that the last unformed stool was passed before the start of clinical cure. In the intent-to-treat population (n=264), the median TLUS was 46.0 hours for rifamycin SV MMX (n=199) compared with 68.0 hours for placebo (n=65), p=0.0008. The drug was well tolerated. The most frequent adverse events were headache, diarrhea, infectious diarrhea, constipation, amoebic dysentery and gastrointestinal infection. A second phase III trial of rifamycin SV MMX, compared to ciprofloxacin,

April 9, 2012

Ventria Bioscience issued results from a phase II trial of VEN100, human recombinant lactoferrin, for the treatment of antibiotic-associated diarrhea. This randomized, double-blind, placebo-controlled study enrolled 30 high-risk subjects taking antibiotics. The subjects received VEN100 or placebo for eight weeks. The results showed a 52% relative risk reduction and a 47.9% absolute risk reduction in the incidence of diarrhea in the placebo versus VEN100 treatment groups (92.3% versus 44.4%, respectively; P≡0.023). VEN100 was safe and well tolerated, with no observed adverse events in the study.

February 20, 2012

Soligenix issued preliminary results from a phase I/II trial of SGX201, a time-release formulation of oral beclomethasone dipropionate, for the prevention of acute radiation enteritis. This multicenter, open-label, sequential, dose-escalation study, dubbed BDP-ENT-01, enrolled 16 subjects with rectal cancer who were scheduled to undergo concurrent radiation and chemotherapy prior to surgery. The subjects received 1, 2, 3 or 4mg of SGX201 three times daily, with dosing administered throughout the duration of radiation therapy plus one week. Oral administration of SGX201 was safe and well tolerated across all four dose groups. There was also evidence of a potential dose response with respect to diarrhea, nausea and vomiting and the assessment of enteritis. The incidence of diarrhea was lower than that seen in historical control data.

August 1, 2011

Lexicon Pharmaceuticals released results from a phase I trial of LX1033 for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-d). This randomized, placebo-controlled trial enrolled 32 healthy subjects who received LX1033 at 250 mg, 500 mg, or 750 mg three times daily, 1,000 mg given twice daily, or placebo. The treatment duration was 14 days. Top-line results demonstrated that LX1033 was well tolerated at all doses and produced a statistically significant reduction in serotonin synthesis compared to placebo, as measured by both plasma (p<0.001) and urinary (p<0.01) 5-hydroxyindoleacetic acid (5-HIAA), a biomarker for serotonin synthesis.

February 21, 2011

Glenmark issued results from a phase II trial of crofelemer for the treatment of acute watery diarrhea. This multi-center, placebo controlled trial enrolled hospitalized adult subjects with mild to moderate acute watery diarrhea. The subjects received Crofelemer (125, 250 or 500 mg) or placebo over a period of three days, with a follow-up period of 30 days. For the efficacy parameter of stool frequency, there was a significant difference in the reduction of number of stools per day during the three day treatment period between both the lowest and highest crofelemer doses versus placebo. Crofelemer was safe, with no apparent differences in the adverse event profile when compared to placebo.

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