Sucampo and Takeda Initiate Global Pivotal Phase 3 Program of Lubiprostone in Pediatric Functional Constipation

BETHESDA, Md. and DEERFIELD, Ill., Dec. 17, 2013 (GLOBE NEWSWIRE) -- Sucampo Pharmaceuticals, Inc. SCMP ("Sucampo") and its development and commercialization partner Takeda Pharmaceuticals ("Takeda") today announced the initiation of a global pivotal Phase 3 clinical program of lubiprostone in pediatric functional constipation. Functional constipation is a very common gastrointestinal complaint in children and is on the rise. An analysis of longitudinal data in the United States showed a nearly 4-fold increase in rates of constipation over the last decade.¹

Lubiprostone is the world's first chloride channel activator that increases intestinal fluid secretion, softens stools and increases motility in the intestine, thereby facilitating the passage of stool and alleviating symptoms associated with chronic idiopathic constipation. This Phase 3 program was preceded by an open-label trial in 124 patients aged 3 to 17 years, which suggested that lubiprostone warrants further investigation as a potential treatment for children and adolescents with functional constipation.

Estimates of the prevalence rate of functional constipation in the pediatric population worldwide have varied from 4 to 37%.² Only 50 to 70% of children with functional constipation demonstrate long-term improvement with the current treatments.³

"I am very pleased to be participating in this pivotal program which will study lubiprostone for pediatric functional constipation," said Paul Hyman, MD, Investigator and Professor of Pediatrics, Division Head, Gastroenterology, Children's Hospital at New Orleans, Louisiana State University Health Science Center. "There is an unmet need for alternatives to traditional laxative therapy in the pediatric population, and there are currently no prescription products indicated for long-term use in this population. We look forward to conducting this study to determine whether lubiprostone may be a valuable treatment alternative for these pediatric patients."

This Phase 3 program consists of two well-controlled pivotal studies with similar design – one testing lubiprostone capsules in patients 6 to 17 years of age and another testing lubiprostone liquid formulation in patients aged 6 months to under 6 years. Sucampo also plans to evaluate the long-term safety of lubiprostone in these populations through two open-label extension studies.

The first Phase 3 trial in the program, which has just been initiated, is a randomized, placebo-controlled, double-blind study of the efficacy, safety and pharmacokinetics of lubiprostone in pediatric subjects between the ages of 6 to 17. The trial is expected to enroll more than 500 patients with pediatric functional constipation at up to 100 sites across the United States, Canada, and Europe. Subjects will be treated for 12 weeks with weight-based dosages of 12 mcg or 24 mcg twice daily (BID). The primary endpoint for this trial is overall spontaneous bowel movement (SBM) response. An SBM is a bowel movement that occurs without the use of another constipation treatment such as a laxative, enema, or suppository, during the 24 hours prior to occurrence.

Sucampo plans to file a supplemental new drug application with the U.S. Food and Drug Administration following program completion, which is anticipated by early 2016.

About Pediatric Functional Constipation

The symptoms of pediatric functional constipation include infrequent bowel movements (BMs), hard stools, large diameter stools and painful passage of stools. Rome III diagnostic criteria for childhood functional constipation dictate that such symptoms occur at least once per week for at least 2 months prior to diagnosis. Children may also experience fecal retention due to withholding.¹ There is a tendency to avoid defecation and withhold BMs as a result of pain experienced from the passage of large stools. This withholding of BMs can result in episodes of fecal incontinence. Ninety percent of pediatric constipation is functional constipation and it occurs in all age groups.⁴

About lubiprostone

Amitiza^® (lubiprostone) capsules are indicated for the treatment of chronic idiopathic constipation (CIC) in adults and opioid induced constipation (OIC) in adults with chronic, non-cancer pain (24 mcg twice daily). The effectiveness in patients with OIC taking diphenylheptane opioids (e.g., methadone) has not been established. Amitiza is also indicated for irritable bowel syndrome with constipation (IBS-C) in women > 18 years old (8 mcg twice daily).

Important Safety Information

Amitiza is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be thoroughly evaluated by the treating healthcare provider (HCP) to confirm the absence of such an obstruction prior to initiating Amitiza treatment.

Patients taking Amitiza may experience nausea. If this occurs, concomitant administration of food with Amitiza may reduce symptoms of nausea. Patients who experience severe nausea should inform their HCP.

Amitiza should not be prescribed to patients that have severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment. Patients should be instructed to discontinue Amitiza and inform their HCP if severe diarrhea occurs.

Patients taking Amitiza may experience dyspnea within an hour of first dose. This symptom generally resolves within three hours, but may recur with repeat dosing. Patients who experience dyspnea should inform their HCP. Some patients have discontinued therapy because of dyspnea.

In clinical trials of Amitiza (24 mcg twice daily vs placebo; N=1113 vs N=316, respectively) in patients with CIC, the most common adverse reactions (incidence > 4%) were nausea (29% vs 3%), diarrhea (12% vs 1%), headache (11% vs 5%), abdominal pain (8% vs 3%), abdominal distension (6% vs 2%), and flatulence (6% vs 2%).

In clinical trials of Amitiza (24 mcg twice daily vs placebo; N=860 vs N=632, respectively) in patients with OIC, the most common adverse reactions (incidence > 4%) were nausea (11% vs 5%) and diarrhea (8% vs 2%).

In clinical trials of Amitiza (8 mcg twice daily vs placebo; N=1011 vs N=435, respectively) in patients with IBS-C the most common adverse reactions (incidence > 4%) were nausea (8% vs 4%), diarrhea (7% vs 4%), and abdominal pain (5% vs 5%).

Concomitant use of diphenylheptane opioids (e.g., methadone) may interfere with the efficacy of Amitiza.

The safety of Amitiza in pregnancy has not been evaluated in humans. Based on animal data, Amitiza may cause fetal harm. Amitiza should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when Amitiza is administered to a nursing woman. Advise nursing women to monitor infants for diarrhea.

Reduce the dosage in CIC and OIC patients with moderate and severe hepatic impairment. Reduce the dosage in IBS-C patients with severe hepatic impairment.

Please visit www.sucampo.com/products for complete Prescribing Information and for further information.

About Sucampo Pharmaceuticals, Inc.

Sucampo Pharmaceuticals, Inc. is focused on the discovery, development and commercialization of drugs based on ion channel activators knows as prostones. Discovered by the company's scientific founder, prostones are naturally occurring fatty acid metabolites with unique physiological activities. Sucampo has two marketed products – AMITIZA and RESCULA^® – and a pipeline of prostone-based product candidates in clinical development. A global company, Sucampo is headquartered in Bethesda, Maryland, and has operations in the United Kingdom, Switzerland and Japan. For more information, please visit www.sucampo.com.

The Sucampo logo and the tagline, The Science of Innovation, are registered trademarks of Sucampo AG. AMITIZA is a registered trademark of Sucampo AG. RESCULA is a registered trademark of R-Tech Ueno, Ltd, and has been licensed to Sucampo AG.

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About Takeda Pharmaceuticals U.S.A., Inc. and Takeda Development Center Americas, Inc.

Based in Deerfield, Ill., Takeda Pharmaceuticals U.S.A., Inc. and Takeda Development Center Americas, Inc. are subsidiaries of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. The respective companies currently market oral diabetes, insomnia, rheumatology, gastroenterology and cardiovascular disease treatments and seek to bring innovative products to people through a pipeline that includes compounds in development for diabetes, gastroenterology, neurology and other conditions. To learn more about these Takeda companies, visit www.takeda.us.

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Sources:

1. Rajindrajith S. et al Constipation in Children: Novel Insight Into Epidemiology, Pathophysiology and Management. J Neurogastroenterol Motil 2011 January;17(1):35–47.

2. Loening-Baucke V. Prevalence rates for constipation and faecal and urinary incontinence. Arch Dis Child 2007 Jun;92(6):486-9.

3. Biggs WS. et al Evaluation and treatment of constipation in infants and children. Am Fam Physician 2006 Feb;73(3):469–77.

4. Mugie S. et al Constipation in childhood. Nature Reviews Gastroenterology and Hepatology 2011 Sept;8:502-511