Chronic 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).

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 12, 2011

Furiex issued results from a phase II trial of MuDelta for diarrhea-predominant irritable bowel syndrome. This 12-week randomized, double-blind, placebo-controlled study enrolled 807 subjects who received twice daily (BID) treatment with either placebo or MuDelta at doses of 5, 25, 100 or 200 mg. The 5 mg dose group was dropped after a planned interim analysis, due to limited efficacy, while the other three doses were continued. The primary endpoint, a composite analysis of stool consistency and abdominal pain at week four compared with baseline symptoms, was met with statistical significance over placebo. The rates of treatment response were 12% for MuDelta at 25 mg BID (p≡0.041) and 13.8%; for Mu Delta 200 mg BID (P≡0.015) compared to 5.7% for placebo. Secondary endpoints were also reached at week 12, including relief of IBS-D symptoms and quality of life improvements. MuDelta was well-tolerated and had a favorable safety profile.

March 16, 2009

AGI Therapeutics issued positive results from a phase II trial of AGI-004, a transdermal patch for the treatment of chemotherapy-induced diarrhea (CID). This trial enrolled 64 subjects across Europe and evaluated two doses of the AGI-004 transdermal patch, applied once-daily, or placebo. The co-primary endpoints were a reduction in the incidence of patient-recorded diarrhea (response defined as less than four bowel movements per day) and reduction in the number of bowel movements per day. A reduction in the incidence of diarrhea was reached with statistical significance at the higher of two doses of AGI-004 when compared with placebo. This response for the higher dose of AGI-004 was further supported by a statistically significant difference in the secondary endpoint of patient recorded severity of diarrhea. A reduction in the number of bowel movements per day showed a positive trend but did not reach statistical significance. Positive trends were observed in the other secondary measurement of reduction in the use of rescue anti-diarrheal medications. Benefits in the primary endpoints were observed with the lower dose however, statistical significance was not reached.

March 2, 2009

Optimer reported positive results from a phase III trial of Prulifloxacin for the treatment of bacterial gastroenteritis (travelers diarrhea). This randomized, double-blind, placebo-controlled study, dubbed OPT-099-002, enrolled 373 adult subjects who were traveling through India, Guatemala or Mexico and diagnosed with bacterial gastroenteritis. The subjects received either 600mg of oral Prulifloxacin or placebo, once daily over three days. The primary efficacy endpoint was Time to the Last Unformed Stool, defined as the time in hours from the first dose of study medication to the passage of the last unformed stool (TLUS). Prulifloxacin was statistically superior to placebo in TLUS in both the modified intent-to-treat population (n≡200) and microbiologically evaluable population (n≡173). The median TLUS for the Prulifloxacin treatment arm was 32.8 hours; (p-value of <0.0001 versus placebo). Prulifloxacin was generally well tolerated and had a similar safety profile compared to placebo.

April 21, 2008

Napo and Glenmark released positive results from a phase II trial of crofelemer for the treatment of acute infectious diarrhea. This randomized, parallel group, double-blind, placebo-controlled study enrolled ninety-eight adult subjects in India. All subjects had experienced acute diarrhea, defined as the occurrence of three or more unformed stools (soft or watery consistency) within the twenty four hour period preceding entry into the study. The subjects received 250 mg of crofelemer four times per day until recovery or for a maximum of three days. The primary endpoint was improvement in gastrointestinal symptoms, including stool weight, stool frequency, stool consistency and duration of diarrhea. These were recorded by the investigators at baseline, and days one, two and three of treatment. Statistically significant improvements were reached in all the primary endpoints. Overall clinical success was achieved in 79.1% of the evaluable subjects receiving crofelemer compared to 28.2% of the evaluable subjects receiving placebo. Crofelemer was well tolerated and most adverse events were mild to moderate in severity and not different from the placebo group. Based on the results the companies plan to begin another dose-ranging trial in 2008, investigating lower doses and lower dosing frequency.

January 7, 2008

Dynogen reported positive results from a phase II trial of DDP-225 for the treatment of irritable bowel syndrome with diarrhea (IBS-d). This randomized, double-blind, placebo controlled trial enrolled eighty-seven women in the United States and Canada. The primary endpoint of adequate relief of pain and discomfort was achieved. The 1 mg dose of DDP225 administered once daily for eight weeks achieved a 71% response rate compared to a 25% response rate for placebo (p=0.009). Treatment was safe and well tolerated. Based on the results, Dynogen planned to initiate phase IIb trials in 2008.

July 16, 2007

Genzyme reported negative results from a phase III trial of tolevamer liquid for the treatment of Clostridium difficile associated diarrhea (CDAD). This randomized double-blind trial, dubbed PACT (Polymer Alternative for CDAD Treatment), enrolled 1,100 subjects internationally. Half of the subjects received liquid tolevamer and half received metronidazole and vancomycin. The primary endpoint was non-inferiority against the standard oral dose of vancomycin, as measured by the percent of subjects with resolution of CDAD. This endpoint was not met. A second phase III trial is currently underway. Genzyme plans to fully analyze the combined data in order to determine a future course of action.

July 9, 2007

Cosmo reported positive preliminary results from a phase II/III trial of Rifamycin for the treatment of infectious diarrhea. This placebo controlled, randomized, double blind trial enrolled 120 subjects in South Africa. Subjects were treated with Rifamycin or Normix (rifaximin), the standard of care, administered as a 200 mg tablet, 4 times per day for 3 days. The primary endpoint was to establish non-inferiority between the two treatments and the time from first ingestion of tablet to the last unformed stool. Initial data suggest that this was achieved. Cosmo plans to further analyze the results and move forward with the development of Rifamycin.

April 30, 2007

Iomai announced positive results from a phase II trial of the TIM ETEC vaccine patch for the treatment of traveler's diarrhea. This dose-ranging trial enrolled 400 subjects who received four different doses of the vaccine (7.5 micrograms, 22.5 micrograms, 37.5 micrograms and 50 micrograms) or placebo. IgG antibody levels were checked at 21 and 42 days. Results revealed that the patch elicited an immune response in 95% of the subjects tested, at all dose levels. Iomai plans to initiate phase III trials later in 2007.

March 12, 2007

Iomai issued positive results from a phase II trial of their TIM ETEC vaccine patch for the treatment of traveler's diarrhea caused by enterotoxigenic Escherichia coli. This double-blind trial enrolled 27 subjects who were traveling to Mexico or Guatemala. Subjects received three doses of the vaccine or placebo and were then given a dose of E. coli larger than would be expected under natural conditions. Both groups met the definition of moderate to severe illness, however the group receiving the vaccine had significantly fewer loose stools (p=0.04) and lower mean weights of the loose stools (p<0.05). In addition, only 14% of the subjects in the vaccine group required intravenous fluids versus 40% in the placebo group. Also, an increase in antibodies associated with E. coli infection were observed in the vaccine group; 100% had a four-fold increase in serum IgG and 97% had a four-fold increase in IgA. Based on the data, Iomai plans to initiate phase III trials later in 2007.

July 14, 2003

The BioBalance Corp. reported positive results from a pilot study investigating Probactrix, a probiotic oral suspension for the treatment of irritable bowel syndrome (IBS). Probactrix is a formulation of M-17 E. coli which is approved as an OTC pharmaceutical in Russia and as a food supplement in Israel. Results showed eight out of ten subjects that started on placebo dropped out because of infectivity compared with none of the subjects taking ProBactrix. Data demonstrated significant improvement in bowel movement and mucus in stools among subjects taking ProBactrix. The randomized, double blind study enrolled 20 subjects experiencing severe symptoms of diarrhea and constipation. Results were presented at the 2003 Annual Meeting of the American Society of Gastroenterologists.