Balsalazide 3.3 Grams Twice-Daily Shows Significant Improvement in Bowel Function and Some Quality of Life Measures as Early as Week Two
Ulcerative Colitis Patients Reported Improvement in Rectal Bleeding, Bowel Frequency and Bowel Healing, as Well as Emotional and Social Functions
SAN DIEGO, CA, May 20, 2008 – Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced
that as early as two weeks into treatment, patients with mild–to–moderate
active ulcerative colitis taking 3.3 g balsalazide disodium tablets twice–daily versus placebo for active disease management
experienced significantly greater quality of life (QoL) improvements in bowel function, as well as improvement in their emotional state as measured by a variety of factors including feelings of frustration, anger, impatience and anxiety. Balsalazide 1.1 g tablets will be the first 5–ASA
agent for active disease that patients will only need to take twice a day. These data were presented today at the Digestive Disease Week 2008
annual meeting in San Diego, California.
"The quality of life benefits seen with balsalazide's twice–daily dosing regimen enhance the utility of this proven anti–inflammatory agent
and make the 1.1 g tablet an important new treatment option for patients suffering with this debilitating disease," said study author Ellen Scherl,
MD, Director, Jill Roberts Center for Inflammatory Bowel Disease, The New York Presbyterian Hospital, Weill Medical College of Cornell University.
Results
After two weeks, patients taking balsalazide 3.3 g twice–daily reported significantly greater improvement versus placebo across a broad range of measures including bowel symptoms, systemic symptoms, emotional function and social function. Additionally, significantly more patients who received
balsalazide 3.3 g twice–daily reported they were satisfied or very satisfied with treatment versus those taking placebo (73 percent vs. 56 percent
[P=0.0230]) at the end of the eight week trial.
At Two Weeks |
| |
Balsalazide 3.3 g
twice–daily |
Placebo |
Statistical
Significance |
| Mean Bowel Symptom Score |
9.7 points |
6.3 points |
P=0.0043 |
| Mean Emotional Function Score |
11.1 points |
8.2 points |
P=0.0105 |
| Mean Social Function Score |
3.5 points |
2.4 points |
P=0.0043 |
| Mean Total QoL Score |
27.9 points |
20.1 points |
P=0.0064 |
At Eight Weeks |
| Mean Emotional Function Score |
12 points |
10.5 points |
P=0.0192 |
| Mean Social Function Score |
4.7 points |
4.1 points |
P=0.0055 |
| Total QoL Score |
32.7 points |
29.7 points |
P=0.0302 |
| |
Balsalazide 3.3 g Tablets Twice–Daily Effective in Improving Signs and Symptoms of Mild–to–Moderate Disease
Another abstract from the study presented today showed that patients taking three 1.1 g balsalazide tablets twice–daily versus placebo experienced
improvement in their symptoms at week eight, including rectal bleeding (59 percent vs. 42 percent [P=0.01]); bowel frequency (49 percent vs. 37 percent
[P=0.08]); and mucosal appearance (53 percent vs. 37 percent [P=0.02]), significant indicators of bowel healing. Importantly, this improvement
was measured by both patient and physician assessment.
* A significantly larger proportion of patients in the balsalazide 1.1 g twice–daily group vs. placebo experienced improvement in the total Modified
Mayo Disease Activity Index (MMDAI) score at week eight (67 percent vs. 47 percent [P=0.004]).
* A significantly larger proportion of patients in the balsalazide 1.1 g twice–daily group vs. placebo experienced improvement in the physician's
assessment of disease (60 percent vs. 36 percent [P=0.0004]).
A third abstract reported that balsalazide 3.3 g tablets twice–daily were well tolerated with a side effect profile equal to or better than placebo.
The percentage of patients who experienced any adverse events (AEs) was 55 percent for balsalazide 3.3 g tablets twice–daily versus 68 percent
for placebo. The majority of AEs experienced by either group were mild or moderate in intensity. The most common AEs were exacerbation of ulcerative
colitis, headache, diarrhea and abdominal pain.
Twice–Daily Dosing Stands to Improve Patient Compliance
Balsalazide 1.1 g tablets will be the first 5–ASA agent that patients with mild–to–moderate active ulcerative colitis will only need to take twice a day –– standing to improve their adherence to therapy. Despite the effectiveness of oral 5–ASA agents (like balsalazide
1.1 g tablets), a majority of patients do not take their medications as prescribed because of the frequency and number of pills required to control
their symptoms. A study conducted by the Crohn's and Colitis Foundation of America (CCFA) found that 65 percent of patients with ulcerative colitis
are poorly compliant with their medication, citing pill burden and inconvenience associated with the medication as key reasons.
About the Study
Adults (n=250) with mild–to–moderate active ulcerative colitis were randomized to receive either balsalazide 3.3 g twice–daily or placebo
for eight weeks. Patient quality of life was assessed at baseline, week two and week eight (or last treatment) by the inflammatory bowel disease
questionnaire (IBDQ), a 32–item patient questionnaire grouped into four components: bowel symptoms, systemic symptoms, emotional function and
social function. At the end of the study, patients were interviewed to assess satisfaction with treatment.
A colonoscopy or sigmoidoscopy was performed at screening and at week eight or end of treatment. Secondary efficacy endpoints were assessed using the MMDAI at screening, baseline and at week eight. Safety evaluations involved clinical lab assessments (e.g., hematology and blood chemistry) at baseline
and weeks two and eight, with vital sign measurements and AE and concomitant medication documentation at baseline and weeks one, two, four and eight.
About Ulcerative Colitis
Ulcerative colitis is a chronic disease of the colon or large intestine. The disease is marked by inflammation and ulceration of the colon mucosa or innermost
lining. Tiny open sores, or ulcers, form on the surface of the lining, where they bleed and produce pus and mucus. Because the inflammation
makes the colon empty frequently, symptoms typically include diarrhea (sometimes accompanied by blood) and often abdominal pain. The inflammation
usually begins in the rectum and lower colon, but it may also involve the entire colon.
Some people with ulcerative colitis have remissions–periods when the symptoms go away–that last for months or years. However, most patients'
symptoms eventually return. Active therapy is treatment given to treat UC symptoms when they are active. Maintenance therapy refers to treatment
given to patients to enable them to stay in remission, to maintain their health in a disease–free, or limited–disease, state. Maintenance
medications must be taken for a prolonged period of time.
People with ulcerative colitis have abnormalities of the immune system, but it is not known whether these abnormalities are a cause or a result of the disease. The body's immune system is believed to react abnormally to the bacteria in the digestive tract. Ulcerative colitis is not caused by emotional
distress or sensitivity to certain foods or food products, but these factors may trigger symptoms in some people. About 5 percent of people with
ulcerative colitis develop colorectal cancer. The risk of cancer increases with the duration of the disease and how much the colon has been damaged.
For example, if only the lower colon and rectum are involved, the risk of cancer is no higher than normal. However, if the entire colon is involved,
the risk of cancer may be as much as 32 times the normal rate.
About Salix Pharmaceuticals
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 with any required
development and regulatory submission of these products, and market them through the Company's gastroenterology specialty sales and marketing team.
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, aminosalicylates, 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 in 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.
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).
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 for OSMOPREP including BOXED WARNING, please click here.
Important Safety Information about XIFAXAN 550 mg
XIFAXAN® 550 mg is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients ≥18 years of age. In the trials of XIFAXAN for HE, 91% of the patients were using lactulose concomitantly. XIFAXAN has not been studied in patients with MELD scores >25, and only 8.6% of patients in the controlled trial had MELD scores over 19. There is increased systemic exposure in patients with more severe hepatic dysfunction. Therefore, caution should be exercised when administering XIFAXAN to patients with severe hepatic impairment (Child-Pugh C).
XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
Clostridium difficile–associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon which may lead to overgrowth of C difficile. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C difficile may need to be discontinued.
The most common adverse reactions occurring in >8% of patients in the clinical study were edema peripheral (15%), nausea (14%), dizziness (13%), fatigue (12%), ascites (11%), muscle spasms (9%), pruritus (9%), and abdominal pain (9%).
For complete Prescribing Information, please click here.
Important Safety Information about METOZOLV ODT
Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible.
The risk of developing tardive dyskinesia increases with the duration of treatment and the total cumulative dose.
Metoclopramide therapy should be discontinued in patients who develop signs or symptoms of tardive dyskinesia.
There is no known treatment for tardive dyskinesia. In some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped.
Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia.
METOZOLV® ODT
(metoclopramide HCl) is indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal
reflux disease (GERD) who fail to respond to conventional therapy and for the relief of symptoms associated with acute and
recurrent diabetic gastroparesis (diabetic gastric stasis) in adults. Therapy should not exceed 12 weeks in duration. Take on
an empty stomach up to four times daily, at least 30 minutes before eating and at bedtime.
METOZOLV ODT is contraindicated in patients with intestinal obstruction, hemorrhage, or perforation; pheochromocytoma;
known sensitivity or intolerance to metoclopramide; epilepsy; or are receiving concomitant medications with extrapyramidal reactions.
Extrapyramidal symptoms (EPS), manifested primarily as acute dystonic reactions, occur in approximately 1 in 500 patients treated with the
usual adult dosages of 30 to 40 mg/day of metoclopramide. These usually are seen during the first 24 to 48 hours of treatment with metoclopramide,
occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at higher doses.
Drug-induced Parkinsonism can occur during metoclopramide therapy, more commonly within the first 6 months after beginning treatment,
but also after longer periods. Patients with a history of Parkinson’s disease should be given metoclopramide cautiously, if at all,
since such patients can experience exacerbation of Parkinsonian symptoms when taking metoclopramide.
There have been rare reports of an uncommon but potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) associated
with metoclopramide. Clinical manifestations of NMS include hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability.
The management of NMS should include immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy.
Depression associated with metoclopramide use has occurred in patients with and without a history of depression.
For those patients with a prior history of depression, metoclopramide should only be given if the expected benefits outweigh the potential risks.
In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, caution should be exercised
when metoclopramide is used in patients with hypertension. Any rapid rise in blood pressure associated with METOZOLV ODT use should result in immediate
cessation of metoclopramide use in those patients.
Since metoclopramide produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing
fluid retention and volume overload. If these side effects occur at any time in any patients during metoclopramide therapy, the drug should be discontinued.
Adverse reactions, especially those involving the nervous system, may occur after stopping the use of METOZOLV ODT.
In clinical studies, the most frequently reported adverse events (≥2% occurrence) were headache, nausea, fatigue, somnolence, and vomiting.
Full Prescribing Information for METOZOLV ODT, including BOXED WARNING.