Study demonstrated AMITIZA (lubiprostone) showed efficacy
Additional safety study finds AMITIZA also provided improvements in symptoms of chronic idiopathic constipation in long-term use
Results of a secondary analysis of two pivotal studies were presented today at the 71st Annual Meeting of the American College of Gastroenterology (ACG), and showed that 60 percent of patients treated with AMITIZA (TM) (lubiprostone) experienced a spontaneous bowel movement (SBM) within 24 hours of treatment, and 80 percent experienced a SBM within 48 hours of treatment. Additionally, AMITIZA, the first selective chloride channel activator approved by the FDA for the treatment of chronic idiopathic constipation in adults, showed improvement in long-term symptom relief of this disorder with significant improvements in constipation severity, abdominal bloating and discomfort for up to 12 months.
"These results are encouraging for physicians who treat patients with constipation because there are few treatments approved for chronic constipation that can be used long term," said Satish Rao, M.D., professor of medicine and director, Neurogastroenterology and GI Motility at University of Iowa. "These data indicate that lubiprostone may provide rapid and long-term relief of symptoms."
Constipation, one of the most common digestive complaints, accounts for more than 2.5 million doctor visits in the U.S. each year according to the ACG. It is a condition that often requires rapid and predictable relief of symptoms with limited long-term treatment options. In clinical studies, relief was defined as three or more SBMs per week.
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.
Study Design: Spontaneous Bowel Movements within 24 Hours and 48 Hours
To determine the onset of action of AMITIZA within 24 and 48 hours, individual and pooled results from two well-controlled Phase III trials were examined: 239 participants received AMITIZA 24 mcg twice daily and 240 participants received placebo. Data on time to first SBM and percentage of patients experiencing a SBM within 24 and 48 hours following initial study-drug administration were compared by study and pooled between treatment groups (placebo vs. AMITIZA). For each study, the time to first SBM was significantly shorter for patients taking AMITIZA compared with those taking placebo (P is less than or equal to 0.006).
- In the individual studies, 57 to 63 percent of patients treated with AMITIZA and 32 to 37 percent of placebo patients had a SBM within 24 hours (P is less than or equal to 0.0024).
- At the 48-hour timepoint in the individual studies, a SBM occurred in 79 to 80 percent of patients treated with AMITIZA vs. 61 to 66 percent of placebo patients (P is less than or equal to 0.0258).
- In the pooled analysis, 60 percent of patients treated with AMITIZA had a SBM within 24 hours and 80 percent had a SBM within 48 hours, compared with 35 and 63 percent of placebo patients, respectively (P is less than 0.0001).
Study Design: Long-Term Use of AMITIZA
To evaluate the long-term safety of AMITIZA, a 48-week, open-label trial of patients who had not received AMITIZA before was conducted. In total, 324 participants with chronic idiopathic constipation received AMITIZA 24 mcg taken twice daily.
The findings revealed that AMITIZA was generally well tolerated throughout the study's duration. Sixty-seven percent of patients experienced at least one treatment-related adverse event (AE). The most common treatment-related AEs included nausea (30.2%) and diarrhea (19.4%). Improvements in assessments of constipation severity, abdominal bloating and abdominal discomfort were statistically significant at all visits compared to baseline (P is less than or equal to 0.001).
Further, patients were asked to assess constipation severity and abdominal symptoms of bloating and discomfort using a 5-point scale where 0=absent, 1=mild, 2=moderate, 3=severe and 4=very severe, at each study visit (approximately every 6 weeks). Specifically:
- Constipation severity was improved by an average of 1.11 points at Week 1 (N=320), 1.17 points at Week 24 (N=183), 1.28 points at Week 48 (N=152) and 0.99 points for the last on-drug measurement (N=320) from a mean baseline value of 2.69 (N=320).
- Abdominal bloating was improved by an average of 0.70 points at Week 1 (N=320), 0.80 points at Week 24 (N=183), 0.88 points at Week 48 (N=152) and 0.68 points for the last on-drug measurement (N=320) from a mean baseline value of 1.88 (N=320).
- Abdominal discomfort was improved by an average of 0.65 points at Week 1 (N=320), 0.66 points at week 25 (N=183), 0.78 points at Week 48 (N=152) and 0.60 points for the last on-drug measurement (N=320) from a mean baseline value of 1.60 (N=320).
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 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.
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.
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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