Salix Presents New Phase II Data Evidence Demonstrating the Clinical Utility of Rifaximin in Irritable Bowel Syndrome (IBS)
Results Presented at American College of Gastroenterology Annual Meeting Demonstrate Quality of Life Benefits and IBS Symptom Severity as Predictor of Clinical Response
ORLANDO, FL, October 6, 2008 – Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced
findings from two analyses of a Phase II clinical trial that demonstrate the utility of rifaximin, a non–absorbed, gut–selective antibiotic, in the treatment of patients with diarrhea–predominant
irritable bowel syndrome (IBS). Data presented at the annual meeting of the American College of Gastroenterology (ACG) showed that patients treated with rifaximin demonstrated that the severity of baseline IBS symptoms of abdominal pain and bloating predicted clinical response to rifaximin
and demonstrated statistically greater clinical improvement in quality of life compared with placebo.
"The latest findings, along with previously reported data, suggest a potential therapeutic role for rifaximin – a non–absorbed and gut–selective
antibiotic – in patients with irritable bowel syndrome," said William D. Chey, MD, professor of medicine in the Division of Gastroenterology
at the University of Michigan, and director of the Gastrointestinal (GI) Physiology Laboratory at the University of Michigan Medical Center.
"The evidence in support of rifaximin will be discussed in a forthcoming evidence–based review from the American College of Gastroenterology
on the management of IBS."
Improvements in Quality of Life
In a poster presentation at ACG, Dr. Chey and colleagues reported that a 2–week course of rifaximin (1100 mg/day) significantly improved quality of life (QOL) measures, compared with placebo (Poster #P691, Monday, October 6, 10:30 am – 4:00 pm). In a Phase II multi–center, double–blind,
placebo–controlled trial, 191 adult patients diagnosed with diarrhea–predominant IBS (IBS–D) by Rome II criteria were randomized
to receive rifaximin 550 mg twice daily (b.i.d.) and 197 patients were randomized to placebo. Following a 2–week initial treatment period,
both groups of patients received placebo for an additional 14 days. Quality of life was assessed via the 34–item IBS–QOL questionnaire
at baseline and 4 weeks after initiating treatment. Each item was scored on a 5–point scale (1=not at all; 2=slightly; 3=moderately; 4=quite
a bit; 5=extremely or a great deal); results for composite and subscale scores were converted to a scale ranging from 0 to 100, with higher scores
indicating better QOL.
At Week 4, the mean improvement from baseline in the overall QOL score was significantly greater with rifaximin compared with placebo (20.4 vs. 15.8, respectively;
p=0.020). Patients in the rifaximin group also reported significantly greater mean improvement from baseline in QOL subscale scores for
dysphoria (restlessness or agitation, 24.8 vs. 19.8; p=0.027), body image (20.1 vs. 14.6; p=0.012), health worry (16.0 vs. 12.2; p=0.047), social reaction
(17.3 vs. 13.2; p=0.047), and relationships (14.9 vs. 10.7; p=0.030), compared with placebo. Rifaximin was well tolerated in the study, with
a similar incidence of adverse events compared with placebo.
Severity of Baseline Symptoms as Predictor of Clinical Response
In a separate poster presentation from the same study, Mark Pimentel, MD, and colleagues reported that the severity of baseline symptoms of abdominal pain
and bloating influenced the response to rifaximin treatment (Poster #P1065, Tuesday, October 7, 10:30am – 4:00pm). The co–primary endpoints
in this analysis assessed weekly yes/no responses to questions regarding adequate relief of global IBS symptoms and IBS–associated bloating.
Clinical response was defined as adequate relief for at least 2 of the final 3 treatment weeks (Week 2, 3 or 4). Severity of baseline IBS symptoms
was evaluated as a potential confounder of clinical response and was categorized as mild/moderate or severe based on a mean score of ≤4 vs. >4
(on a 7–point scale [0=not bothersome; 6=very bothersome]) for bloating and abdominal pain.
A significantly larger percentage of patients treated with rifaximin reported adequate relief of global IBS symptoms (52% vs. 44% for placebo; p=0.03) and bloating (46% vs. 40%; p=0.04), compared with placebo–treated patients. In patients with mild/moderate abdominal pain, rifaximin produced a greater degree of improvement, compared with placebo, in global symptoms of IBS (50% vs. 39%, respectively; p=0.04) and bloating (44% vs. 35%; p=0.09).
Similarly, in patients with mild/moderate bloating, rifaximin treatment was associated with greater improvement, compared with placebo, in global IBS symptoms (56% vs. 41%, respectively; p=0.006) and bloating (47% vs. 36%; p=0.03). However, rifaximin was not significantly superior to placebo in improving global IBS symptoms or bloating in patients who had severe baseline abdominal pain or bloating.
"The symptom–based criteria that are used for enrolling patients with IBS in clinical trials are overly broad and often lead to enrollment of individuals
ranging from mild to severe, despite the possibility that patients with severe IBS symptoms may respond differently to treatment compared with
individuals with moderate complaints," commented Dr. Pimentel, who is director of the Gastrointestinal Motility Program and Laboratory at Cedars–Sinai
Medical Center, and associate professor in residence for the David Geffen School of Medicine at the University of California, Los Angeles
(UCLA). "Our data demonstrate that patients with mild/moderate IBS symptoms are more likely than those with severe disease to achieve symptomatic
relief with rifaximin. Clinical trials evaluating the efficacy of IBS therapies should therefore account for baseline symptom severity because of the
potential impact of these symptoms on therapeutic efficacy. Additionally, incorporating severity assessments into clinical practice may improve treatment
success in patients with IBS."
Other Rifaximin–related Presentations at ACG
In addition to the presentations by Drs. Chey and Pimentel, the ACG program includes the following rifaximin–related presentations:
* Poster #P495: Neff, et al. Clostridium difficile infection was not detected in patients who received rifaximin for hepatic encephalopathy in community
and university practices. Monday, October 6, 10:30am – 4:00pm.
* Poster #P549: Finkelstein, et al. Efficacy of rifaximin as long–term maintenance therapy for refractory Crohn's disease. Monday, October 6, 10:30am
– 4:00pm.
* Poster #P1046: Bosworth, et al. Long–term follow–up of the use of rifaximin in maintaining clinical remission in moderate and severe Crohn's
disease. Tuesday, October 7, 10:30am – 4:00pm.
* Poster #P670: Shafran, et al. Comparison of computed tomographic enterography with standard diagnostic assessments for detecting active Crohn's disease.
Monday, October 6, 10:30am – 4:00pm.
* Poster #P544: Shafran, et al. Rifaximin monotherapy was effective in patients with newly diagnosed Crohn's disease. Monday, October 6, 10:30am –
4:00pm.
* Poster #P669: Shafran, et al. Monitoring patients with ulcerative colitis in community–based practice to improve adherence. Monday, October 6, 10:30am – 4:00pm.
* Poster #P700: Jolley. Efficacy of rifaximin for the treatment of symptoms associated with irritable bowel syndrome. Monday, October 6, 10:30am –
4:00pm.
* Poster #P1074: Pimentel, et al. A combination of rifaximin and neomycin is most effective in treating patients with methane on lactulose breath test.
Tuesday, October 7, 10:30am – 4:00pm.
* Poster #P448: Weinstock, et al. Rifaximin Improves Restless Legs Syndrome Associated With Bacterial Overgrowth. Monday, October 6, 10:30am – 4:00pm.
* Poster #P447: Weinstock, et al. Celiac disease is associated with restless legs syndrome. Monday, October 6, 10:30am – 4:00pm.
* Poster #P308: Weinstock, et al. Crohn's Disease is Associated with Restless Legs Syndrome: A New Extraintestinal Manifestation. Sunday, October 5, 3:30pm
– 7:00pm.
About IBS
Among one of the most common chronic conditions, irritable bowel syndrome (IBS) affects approximately 14% of adults in the United States. IBS includes altered bowel habits with abdominal pain and discomfort. Among other contributors, recent science has shown that alterations in gut flora / bacteria have
been identified as a potentially important contributor to the pathophysiology of IBS. Small intestinal bacterial overgrowth, a condition associated
with excessive numbers of bacteria in the small intestine, may underlie some of the gastrointestinal symptoms associated with IBS.
About XIFAXAN
Rifaximin, which Salix markets in the United States under the trade name XIFAXAN® (rifaximin), currently is approved for the treatment of
patients, 12 years of age or older, with travelers' diarrhea caused by non–invasive strains of Escherichia coli.
XIFAXAN® (rifaximin) is a gut–selective antibiotic with negligible systemic absorption (<0.4%) and broad–spectrum activity in
vitro against both gram–positive and gram–negative pathogens. Rifaximin has a similar tolerability profile to that of placebo and has activity against the most common TD pathogens.
XIFAXAN is under investigation in the United States as a treatment for irritable bowel syndrome. In the United States, the FDA granted marketing clearance
for XIFAXAN tablets 200 mg indicated for the treatment of patients (≥12 years of age) with travelers' diarrhea caused by noninvasive strains of Escherichia coli. XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. XIFAXAN should be discontinued if diarrhea symptoms get worse or persist more than 24–48 hours and alternative
antibiotic therapy should be considered. In clinical trials, XIFAXAN was generally well tolerated. The most common side effects (vs. placebo) were
flatulence 11.3% (versus 19.7%), headache 9.7% (versus 9.2%), abdominal pain 7.2% (versus 10.1 %) and rectal tenesmus 7.2% (versus 8.8%).
Rifaximin has been used in Italy for 23 years and is approved in 23 countries. Salix acquired rights to market rifaximin in North America from Alfa Wassermann
S.p.A. in Bologna, Italy. Alfa Wassermann markets rifaximin in Italy under the trade name Normix®.
About Salix
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, North Carolina, develops and markets prescription pharmaceutical products for the treatment of gastrointestinal
diseases. Salix's strategy is to in–license late–stage or marketed proprietary therapeutic drugs, complete any required development and regulatory submission of these products, and market them through the Company's 150–member gastroenterology specialty sales and marketing
team.
Salix also markets OSMOPREP® (sodium phosphate monobasic monohydrate, USP and sodium phosphate dibasic anhydrous, USP) Tablets, MOVIPREP®
(PEG 3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate and Ascorbic Acid for Oral Solution), VISICOL®
(sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets, COLAZAL® (balsalazide
disodium) Capsules 750 mg, PEPCID® (famotidine) for Oral Suspension, Oral Suspension DIURIL® (Chlorothiazide), AZASAN®
(azathioprine Tablets, USP, 75/100 mg) , ANUSOL–HC® 2.5% (Hydrocortisone Cream, USP), ANUSOL–HC®
25 mg Suppository (Hydrocortisone Acetate), PROCTOCORT® Cream (Hydrocortisone Cream, USP) 1% and PROCTOCORT® Suppository
(Hydrocortisone Acetate Rectal Suppositories) 30 mg. METOZOLV™ ODT (metoclopramide), mesalamine granules, balsalazide tablet,
vapreotide acetate and rifaximin for additional indications are under development.
For full prescribing information on Salix products, please visit www.salix.com or
contact the Company at 919–862–1000.
Salix trades on the NASDAQ Global Select Market under the ticker symbol "SLXP".
For more information please visit our web site at www.salix.com or contact the Company at 919–862–1000. Information on our web site is not incorporated
in our SEC filings.
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APRISO™ is a locally-acting aminosalicylate indicated for the maintenance of remission of ulcerative colitis in patients 18 years and older.
APRISO is contraindicated in patients with hypersensitivity to salicylates, amniosalicylates, or to any of the components of APRISO capsules.
The recommended dose of APRISO is four 0.375 g capsules once daily in the morning (1.5 g/day) with or without food. Because dissolution of the coating of APRISO
granules depends on pH, APRISO should not be coadministered with antacids. Patients with phenylketonuria should be aware that APRISO contains aspartame,
equivalent to 0.56 mg of phenylalanine. In two well-controlled clinical trials, the most common treatment-related adverse events occurring at least 3%
of adult patients taking 1.5 g/day of APRISO were headache (11% vs. 8% for placebo), diarrhea (8% vs. 7% for placebo), upper abdominal pain (5% vs 3% for placebo),
nausea (4% vs 3% for placebo), nasopharyngitis (4% vs 3% for placebo), influenza and influenza-like illness (4% vs 4% for placebo) and sinusitis (3% vs 3% for placebo).
For complete Prescribing Information, please click here.
XIFAXAN® (rifaximin) Tablets are indicated for the treatment of patients (≥12 years of age) with travelers' diarrhea caused by non-invasive strains of
Escherichia coli. XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. XIFAXAN should be
discontinued if diarrhea symptoms get worse or persist more than 24-48 hours and alternative antibiotic therapy should be considered.
In clinical trials, XIFAXAN was generally well tolerated. The most common side effects (vs. placebo) were flatulence 11.3% (vs. 19.7%), headache 9.7% (vs. 9.2%), abdominal pain 7.2% (vs. 10.1 %), rectal tenesmus 7.2%
(vs. 8.8%), defecation urgency 5.9% (vs. 9.2%) and nausea 5.3% (vs. 8.3%).
Consult with your physician to see if this product is right for you.
For complete Prescribing Information, please click here.
MoviPrep® (PEG-3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution) is indicated for cleansing of the
colon as a preparation for colonoscopy in adults 18 years of age or older. MoviPrep is contraindicated in patients who have had a severe hypersensitivity reaction
to any of its components. MoviPrep should be used with caution in patients using concomitant medications that increase the risk of electrolyte abnormalities, in patients with known or suspected hyponatremia,
severe ulcerative colitis, ileus, gastrointestinal obstruction or perforation, gastric retention, toxic colitis, toxic megacolon, or glucose-6-phosphate dehydrogenase deficiency. In clinical trials, abdominal
distention, anal discomfort, thirst, nausea, and abdominal pain were the most common adverse reactions to MoviPrep administration. MoviPrep contains a maximum of 2.33 mg of phenylalanine per treatment.
Consult with your physician to see if this product is right for you.
For complete Prescribing Information, please click here.
Important Safety Information about OsmoPrep
There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior
to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long–term dialysis. While some
cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with
increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using
medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers
[ARBs], and possibly nonsteroidal anti–inflammatory drugs [NSAIDs]).
It is important to use the dose and dosing regimen as recommended (PM/AM split dose).
Please see accompanying brief summary of Prescribing Information for OsmoPrep, including
BOXED WARNINGS.
OsmoPrep® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets are indicated for cleansing
of the colon as a preparation for colonoscopy in adults 18 years of age or older. Considerable caution should be advised before OsmoPrep is used in
patients with severe renal insufficiency, congestive heart failure, ascites, unstable angina, gastric retention, ileus, severe chronic constipation,
bowel perforation, toxic megacolon, gastric bypass or stapling surgery, or hypomotility syndrome. Use with caution in patients with impaired renal
function, patients with a history of seizures or at higher risk of seizure, patients with higher risk of cardiac arrhythmias, known or suspected electrolyte
disturbances (such as dehydration), or people taking drugs that affect electrolyte levels. Patients with electrolyte abnormalities such as
hypernatremia, hyperphosphatemia, hypokalemia, or hypocalcemia should have their electrolytes corrected before treatment with OsmoPrep.
OsmoPrep is contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients, and in patients with
biopsy–proven acute phosphate nephropathy. In clinical trials, the most commonly reported adverse reactions (reporting frequency >3%) were
abdominal bloating, nausea, abdominal pain, and vomiting. It is recommended that patients receiving OsmoPrep be advised to adequately hydrate before,
during, and after the use of OsmoPrep.
For complete Prescribing Information, please click here.