AMITIZA (lubiprostone) Phase III constipation trial results

In recent studies, AMITIZA (tm)(lubiprostone) demonstrated improvements in relief of symptoms associated with irritable bowel syndrome with constipation (IBS-C), such as abdominal bloating and discomfort. Results of sub-analyses from two Phase III chronic constipation studies of AMITIZA, the first selective chloride channel activator approved by the FDA for the treatment of chronic idiopathic constipation in adults, were presented today at the 71st American College of Gastroenterology (ACG) Annual Scientific Meeting.

"The results suggest that AMITIZA may have the potential to improve the symptoms associated with IBS-C, a functional bowel disorder that causes abdominal pain or discomfort, bloating and constipation," said Anthony Lembo, M.D., assistant professor of medicine and director of the Motility Center, Harvard Medical School. "Additional studies are needed to evaluate the potential for AMITIZA with these patients; however, it would benefit patients to have additional treatment options."

According to the ACG, as many as 58 million Americans suffer from irritable bowel syndrome (IBS), a condition that accounts for as much as 50 percent of referrals to gastroenterologists each year, and includes IBS-C.

AMITIZA has a novel mechanism of action that works by activating chloride channels to increase fluid secretion in the intestine, thereby increasing the passage of stool and improving signs and symptoms associated with chronic idiopathic constipation. AMITIZA is the only prescription medication for chronic idiopathic constipation that has been approved by the FDA for use in adults, including those 65 years and over and that has demonstrated effectiveness for use beyond 12 weeks.

About the Study

To evaluate efficacy and symptom improvements in chronic constipation patients treated with AMITIZA with a history of IBS-C, pooled results from two Phase III chronic idiopathic constipation trials were examined. To create an adequate group of IBS-C patients, data from two placebo-controlled clinical trials of 4 weeks were examined together. The pooled IBS-C subgroup consisted of 91 patients: 45 participants received placebo and 46 participants received AMITIZA 24 mcg taken twice daily.

The findings revealed that mean changes in spontaneous bowel movements were significantly greater among the group treated with AMITIZA (4.8 to 6.0 per week) compared to the placebo group (2.8 to 4.0 per week) at all four weekly evaluations (P is less than or equal to 0.0207). Mean stool consistency ratings at all four weekly evaluations were also significantly improved (P is less than 0.0001). Patients reported significantly improved mean bowel straining ratings, with mostly mild straining ratings reported in the AMITIZA group versus mostly moderate straining ratings reported by those taking placebo at all four weekly evaluations (P is less than or equal to 0.0119).

Additionally, assessments of abdominal bloating and discomfort were significantly improved in the group taking AMITIZA versus the placebo group at weeks 3 and 4 (P is less than or equal to 0.0495), and constipation severity ratings were significantly improved in the group receiving AMITIZA versus the placebo group at weeks 1, 3 and 4 (P is less than or equal to 0.0175) and nearly reached significance at week 2 (P=0.0509). Efficacy results were generally similar for both IBS-C and non-IBS-C patients. Comparisons between the groups revealed that fewer IBS-C patients receiving placebo (50%) experienced adverse events (AE) compared with patients receiving AMITIZA (68.9%). The most common AE reported, nausea, had a slightly higher incidence in the IBS-C group treated with AMITIZA versus their non-IBS-C counterparts (35.6% vs. 28.4%, respectively).

AMITIZA, approved by the U.S. Food and Drug Administration (FDA) in January 2006 for the treatment of chronic idiopathic constipation in adults, was developed by Sucampo Pharmaceuticals, Inc., and is jointly marketed in the United States by Sucampo and Takeda Pharmaceuticals North America, Inc.

About Irritable Bowel Syndrome (IBS)

IBS is a chronic disorder characterized by multiple symptoms of abdominal pain and discomfort, bloating and changes of bowel habits such as constipation and/or diarrhea. The condition can significantly interfere with daily activities and reduce patientsí» quality of life, resulting in absences from school, missed work and reduced productivity.

Three main subtypes of IBS exist: with constipation (IBS-C), with diarrhea (IBS-D) and mixed constipation and diarrhea (IBS-M). In IBS-C, symptoms are present for the last 3 months with onset at least 6 months prior to diagnosis. Although people with IBS-C report suffering from many of the same symptoms associated with constipation, the presence of pain and discomfort is what differentiates IBS-C from chronic constipation. The condition is approximately 2 to 2.5 times more prevalent in women than men, and women are more likely to report a history of constipation, whereas men are more likely to report diarrhea.

About Chronic Idiopathic Constipation

Constipation is one of the most common digestive complaints, affecting more than 42 million adults in the United States. It is the cause of 2.5 million visits to physicians and 92,000 hospitalizations annually. Chronic idiopathic constipation is defined by the infrequent or difficult passage of the stool for a period of at least three months. "Idiopathic" means the cause of the constipation is unknown and not due to an underlying illness or medication. The signs and symptoms associated with chronic idiopathic constipation include abdominal discomfort, bloating, straining, and hard or lumpy stools.

About AMITIZA

AMITIZA is indicated for the treatment of chronic idiopathic constipation in the adult population. AMITIZA should not be used in patients with a known hypersensitivity to any components of the formulation and in patients with a history of mechanical gastrointestinal obstruction. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be evaluated prior to initiating AMITIZA treatment.

The safety of AMITIZA in pregnancy has not been evaluated in humans. In guinea pigs, lubiprostone has been shown to have the potential to cause fetal loss. AMITIZA should be used during pregnancy only if the benefit justifies the potential risk to the fetus. Women who could become pregnant should have a negative pregnancy test prior to beginning therapy with AMITIZA and should be capable of complying with effective contraceptive measures.

AMITIZA should not be administered to patients that have severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment. If the diarrhea becomes severe, patients should consult their health professional.

In clinical trials, the most common adverse event was nausea (31%). Other adverse events (greater than or equal to 5% of patients) included diarrhea (13%), headache (13%), abdominal distention (7%), abdominal pain (7%), flatulence (6%), sinusitis (5%) and vomiting (5%).

For full prescribing information, visit www.amitiza.com.

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AMITIZA (tm) is a trademark of Sucampo Pharmaceuticals, Inc.

Sucampo Pharmaceuticals, Inc.

Sucampo Pharmaceuticals, Inc., is an emerging pharmaceutical company based in Bethesda, Md. Sucampo was founded in 1996 by Sachiko Kuno, Ph.D., the company's President and Chair of the Board of Directors, and Ryuji Ueno, M.D., Ph.D., Ph.D., the company's Chief Executive Officer and Chief Scientific Officer. Sucampo focuses on the development and commercialization of drugs based on prostones, a class of compounds derived from functional fatty acids that occur naturally in the human body. The therapeutic potential of prostones was first identified by Dr. Ueno. In January 2006, Sucampo received marketing approval from the FDA for its first product, AMITIZA, for the treatment of chronic idiopathic constipation in adults.

In October 2004, Sucampo entered into an agreement with Takeda Pharmaceutical Company Limited (Osaka, Japan) to co-promote and market AMITIZA in the United States and Canada. Sucampo's specialized sales force complements the efforts of Takeda by focusing on institutional and long-term care facilities. Currently, two pivotal Phase 3 clinical trials of AMITIZA for the treatment of irritable bowel syndrome with constipation (IBS-C) are ongoing, and Phase 2/3 pivotal clinical trials for the treatment of opioid bowel dysfunction (OBD) are expected to commence in early 2007.

To learn more about the company and its products, visit www.sucampo.com.

Takeda Pharmaceuticals North America, Inc.

Based in Deerfield, Ill., Takeda Pharmaceuticals North America, Inc., is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. In the United States, Takeda currently markets oral diabetes, insomnia, cholesterol-lowering and gastroenterology treatments, and has a robust pipeline with compounds in development for diabetes, cardiovascular disease and other conditions. Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. To learn more about the company and its products, visit www.tpna.com.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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