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`XIFAXAN® Trials Initiated in C. difficile-Associated Diarrhea, Irritable Bowel Syndrome and Hepatic Encephalopathy
`
`XIFAXAN® Trials Initiated in C. difficile-Associated
`Diarrhea, Irritable Bowel Syndrome and Hepatic
`Encephalopathy
`
`© 2015 Informa Exhibitions LLC. All rights reserved.
`http://www.endonurse.com/
`By:
`Posted on: 01/12/2006
`
`RALEIGH, N.C. -- Salix Pharmaceuticals, Ltd. reported that initial subjects have been enrolled and dosed in three
`late-stage trials designed to evaluate XIFAXAN® for the treatment of C. difficile-associated diarrhea (CDAD),
`irritable bowel syndrome (IBS) and hepatic encephalopathy (HE). Additionally, initial subjects have been enrolled
`and dosed in a late-stage trial designed to evaluate an 1100 mg tablet formulation of COLAZAL® for the
`treatment of mildly to moderately active ulcerative colitis, and patient enrollment continues in two late-stage
`trials designed to evaluate granulated mesalamine for the maintenance of remission of ulcerative colitis. The
`company intends to pursue label extensions for XIFAXAN for the indications noted above, as well as a
`formulation line extension for the new COLAZAL Tablet and an approval for granulated mesalamine.
`
`XIFAXAN
`C. difficile-Associated Diarrhea (CDAD)
`XIFAXAN (rifaximin), dosed 400 mg three times daily, is being investigated in a vancomycin comparator, 300-
`subject Phase III trial to evaluate the efficacy and safety of XIFAXAN for the treatment of CDAD.
`
`Research by Ciaran Kelly, MD, Harvard School of Medicine; Dan Gerding, Hines VA Hospital and other
`investigators provides the theoretical basis for the development of XIFAXAN as a treatment for CDAD. Poster
`presentations of recent preclinical work by Kelly and Gerding were presented December 16-19, 2005 at the
`Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, D.C. Results of a
`hamster model study of CDAD, conducted by Kelly, demonstrated that rifaximin-treated and vancomycin-
`treated, CDAD-challenged animals achieved similar survival rates. Due to the common recurrence of CDAD in
`the clinical setting, the hamsters were followed after the discontinuation of treatment. Seventy-five percent of
`animals treated with vancomycin developed recurrent C. difficile cecitis (inflammation of the cecum) within 21
`days of stopping therapy whereas none of the rifaximin-treated animals had such a relapse. Results of a
`comparison of rifaximin, rifalazil, metronidazole and vancomycin to investigate the in vitro activity of these
`agents against toxigenic C. difficile clinical isolates, conducted by Gerding, demonstrated that rifaximin and
`rifalazil were the most active agents.
`
`Clostridium difficile, or C. difficile, is the most common causative agent of diarrhea among institutionalized
`patients. Often the administration of antibiotics, especially broad-spectrum antibiotics, disrupts the normal gut
`bacterial flora and increases the concentration of C. difficile. The presence of increased C. difficile can produce
`symptoms ranging from mild diarrhea to life-threatening colitis.
`
`Irritable Bowel Syndrome (IBS)
`XIFAXAN, dosed either 275 mg, 550 mg or 1100 mg twice daily, is being investigated in a placebo-controlled,
`525-subject Phase IIb trial to evaluate the efficacy and safety of XIFAXAN for the treatment of diarrhea-
`associated IBS.
`
`In November 2005 at the American College of Gastroenterology Annual Scientific Meeting, Mark Pimentel,
`Cedars-Sinai Medical Center, presented the findings of a randomized, double-blind, placebo-controlled
`investigation of XIFAXAN in the treatment of IBS. In the 87-subject study, XIFAXAN-treated subjects
`demonstrated a statistically significant improvement versus placebo-treated subjects, and a statistically
`significant number of XIFAXAN-treated subjects demonstrated a greater than 50 percent global improvement
`compared to placebo-treated subjects. This proof-of-concept work provided essential information utilized in the
`design of the company's development program for IBS.
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`XIFAXAN® Trials Initiated in C. difficile-Associated Diarrhea, Irritable Bowel Syndrome and Hepatic Encephalopathy
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`IBS is a bowel disorder characterized by altered bowel function and symptoms including abdominal pain,
`bloating, constipation and diarrhea. This chronic disorder impacts up to 20 percent of the U.S. population, and
`yet, despite its high prevalence, the cause of IBS remains unknown. Current treatments provide only temporary
`symptom relief and do not treat the underlying cause of the symptoms. Recently, bacteria -- specifically an
`overgrowth of bacteria in the small intestine -- have been proposed as a significant causative agent in IBS.
`
`Hepatic Encephalopathy (HE)
`XIFAXAN, dosed 550 mg twice daily, is being investigated in a placebo-controlled, 250-subject Phase III trial to
`evaluate the efficacy and safety of XIFAXAN for the prevention of hepatic encephalopathy.
`
`Hepatic encephalopathy is a metabolic-neurophysiologic syndrome associated with advanced liver disease.
`Symptoms are generally believed to result from the inability of the liver to remove toxic products in the gut.
`These toxic products -- primarily ammonia produced by the intestinal metabolism of nitrogenous compounds --
`are able to pass the blood brain barrier and ultimately reach the central nervous system to produce HE
`symptoms. Neuropsychiatric and neuromuscular symptoms range from mild personality changes, memory loss,
`tremor and asterixis to coma and death.
`
`COLAZAL
`COLAZAL (balsalazide disodium), formulated as an 1100 mg tablet, dosed three tablets twice daily, is being
`investigated in a multi-center, placebo-controlled, double-blind, randomized trial. This Phase III trial, involving
`225 patients, is designed to evaluate the efficacy and safety of 1100 mg balsalazide disodium tablets for the
`treatment of mildly to moderately active ulcerative colitis.
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`GRANULATED MESALAMINE
`Granulated mesalamine is formulated to deliver mesalamine by means of dual-release granules to the distal
`ileum and colon. Granulated mesalamine is being investigated in two 300-subject, multi-center, placebo-
`controlled, double-blind, randomized trials. Enrollment is ongoing in these Phase III trials designed to evaluate
`the efficacy and safety of granulated mesalamine, dosed four 375 mg tablets once daily, for the maintenance of
`remission of ulcerative colitis.
`
`OTHER
`A pediatric trial with COLAZAL is currently ongoing. Enrollment in the trial is anticipated to be complete during
`the first quarter of 2006. A trial with XIFAXAN to assess blood concentrations of a new pediatric suspension is
`being planned for 2006.
`
`New Drug Applications (NDAs) for INKP-102, the next-generation tablet purgative product owned by subsidiary
`InKine; and NRL944, the liquid PEG purgative product acquired recently from Norgine, are under review at the
`U.S. FDA. As required by the Prescription Drug User Fee Act (PDUFA), results of the FDA review are due in mid-
`March 2006 for INKP-102 and late-April 2006 for NRL944.
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`Salix Pharmaceuticals, Ltd., headquartered in Raleigh, N.C., develops and markets prescription pharmaceutical
`products for the treatment of gastrointestinal diseases.
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`Source: Business Wire
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