Digestive Health Matters Vol. 22 No. 3
- GERD Awareness Week
- More from the International Symposium on FGIDs
- A Look Back at 2012 and 2013
- Clinical Corner: Misunderstood Functional GI Disorders
Here are summaries of some recent news about research and treatments for digestive health.
Elobixibat for Treatment of Chronic Constipation Now in Phase 3 Clinical Trials
Phase 3 trials of elobixibat for the indication of chronic idiopathic constipation (CIC) have begun. Ferring Pharmaceuticals reports that two studies are being conducted at close to 200 sites around the world. In Phase 2b clinical trials in the U.S. and Europe, elobixibat (formerly A3309) demonstrated clinically meaningful, statistically significant, and dose-dependent improvements, including increased stool frequency and improved constipation-related symptoms such as straining, stool consistency, and bloating maintained over eight weeks of treatment.
Elobixibat is a first-in-class compound under investigation for treatment of CIC and for IBS with constipation (IBS-C). It works by reducing bile acid absorption in the small intestine. This stimulates bowel movements by increasing fluid secretions and motility in the colon.
Linaclotide is the first medicine approved by the European Commission for the symptomatic treatment of moderate to severe irritable bowel syndrome with constipation (IBS-C) in adult patients. It will become available in an increasing number of European countries during 2013 with the EU brand name Constella.
Linaclotide, a guanylate cyclase type-C (GC-C) agonist, is a prescription drug used to relieve symptoms of abdominal pain, discomfort, bloating, and bowel symptoms in people who have IBS-C or chronic constipation (CC). It has been shown to be safe and effective in trials. It works by increasing the amount of fluid that flows into the bowel, allowing stool to pass more easily, and reducing visceral pain. Linaclotide (Linzess) has been available in the U.S. to treat IBS-C and CC in adults aged 18 and older since 2012. Linzess should not be used in patients 17 years of age or younger. Linzess should not be used in patients with known or suspected mechanical gastrointestinal obstruction. The most common side effect reported during clinical studies was diarrhea.
Linaclotide is being co-produced in the U.S. by Ironwood and Forest. Ironwood has out-licensed linaclotide to Almirall, S.A. for development in Europe; and to Astellas Pharma, Inc. for development in Japan, Indonesia, Korea, the Phillipines, Taiwan, and Thailand.
Rifaximin is an antibiotic currently under investigation for the treatment of nonconstipation Irritable Bowel Syndrome (Non-C IBS) and IBS-related bloating. Rifaximin works by reducing or altering bacteria in the gut. In studies it has been found to improve IBS symptoms of bloating, belly pain, and diarrhea after a 10–14 day course of treatment. It is only slightly absorbed in the gut and is generally tolerated well. Rifaximin has not yet been approved by the U.S. Food and Drug Administration (FDA) for the treatment of IBS.
The makers of lubiprostone (Amitiza) have announced a randomized, placebocontrolled, double-blinded, multi-center study of a liquid form of lubiprostone in adult subjects with chronic idiopathic constipation (CIC). The trial is expected to enroll 152 patients with CIC at approximately 11 sites in the U.S. A liquid formulation could possibly offer an alternative dosing option for a wider range of patients.
Lubiprostone is Approved by the FDA to Treat Opioid-Induced Constipation
Sucampo Pharmaceuticals, Inc. and Takeda Pharmaceuticals U.S.A. Inc. announced earlier this year that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application for lubiprostone (Amitiza) to treat opioidinduced constipation in adult patients with chronic non-cancer pain. The drug was approved to treat chronic idiopathic constipation (CIC) in adults in 2006 and to treat IBS with constipation (IBS-C) in adult women in 2008.
Amitiza is a prescription drug used to relieve abdominal pain, bloating, and straining and produce softer and more frequent bowel movements in men and women who have CIC. It is also used to treat IBS-C in women who are at least 18 years of age. Amitiza works by increasing the amount of fluid that flows into the bowel and allowing the stool to pass more easily.
The drug met the primary endpoint in a Phase 3 clinical trial for the treatment of opioid-induced bowel dysfunction in patients with chronic, non-cancer pain, excluding those taking methadone. Opioids are narcotics (such as morphine and codeine) used to treat pain. A number of gastrointestinal (GI) symptoms are potential side effects of using opioid-based medications. The most common symptom is constipation. Other symptoms may include decreased gastric emptying, abdominal cramping, spasm, bloating, and delayed-GI transit.
New data from a two-year study by NPS Pharmaceuticals supports the long-term use of Gattex for injection in adult patients with short bowel syndrome (SBS). The findings were published as an abstract and presented at the American College of Gastroenterology (ACG) Annual Scientific Meeting and Postgraduate Course in San Diego, CA in October 2013. Patients in the study using Gattex beyond one year continued to be able to reduce their support on parenteral nutrition.
The open-label extension study included 88 adult patients with SBS. Investigators reported that the long-term use of Gattex in patients with SBS resulted in additional, clinically meaningful reductions in the volume and days per week of parenteral support requirements in this extension study. Thirteen patients in the study achieved complete independence from parenteral support with long-term Gattex therapy. No new unexpected safety concerns were observed with long-term Gattex treatment and the product’s safety profile remains consistent with the product’s label.
Gattex is a product of NPS Pharmaceuticals, a specialty pharmaceutical company developing orphan therapeutics for rare gastrointestinal and endocrine disorders. The drug works by regeneration of cells in the intestinal lining, slowing down transit through the gut and increasing blood flow, allowing for increased nutrient absorption. In studies, the drug was associated with achieving and maintaining clinically meaningful reductions in parenteral nutrition (PN) and intravenous (IV) fluid volume in adult subjects with SBS.
Gattex was approved by the U.S. Food and Drug Administration (FDA) in 2012 for treatment of adult patients with SBS who are dependent on parenteral support. To help ensure that the benefits of Gattex outweigh the risks for causing other serious conditions, the drug is approved with a Risk Evaluation and Mitigation Strategy, which patients need to discuss with their doctors. While the researchers found the safety profile to be acceptable, they advise that physicians closely monitor patients beginning the drug for side effects and possible need to adjust dosage.
SBS is a rare condition related to poor absorption of nutrients. It typically occurs in people who have a significant portion of their small intestine removed due to disease or injury. They cannot absorb enough water, vitamins, and other nutrients from food and may then need to use parenteral nutrition and intravenous fluids.
Solesta, a biocompatible tissue bulking agent, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of bowel incontinence in patients 18 years and older who have failed conservative therapy (e.g., diet, fiber therapy, anti-motility medications). The drug has been approved to treat bowel incontinence in the U.S. since 2011 and in Europe since 2006. Bowel incontinence is the involuntary loss of bowel control. While the exact mechanism of action has not been identified, it is thought that the Solesta injections may narrow the anal canal and allow for better control of those muscles.
Solesta is an injectable gel delivered into the anal canal in an outpatient procedure taking approximately 10 minutes without the need for surgery or anesthesia. It should only be administered by physicians experienced in performing anorectal procedures who have successfully completed a comprehensive training and certification program in the Solesta injection procedure. It should not be used in patients who have active inflammatory bowel disease, immunodeficiency disorders, previous radiation treatment to the pelvic area, significant rectal prolapse, active infections, bleeding, tumors or malformations in the anorectal area, rectal distended veins, an existing implant in the anorectal region, or allergy to hyaluronic acid based products.
The most common side effects associated with Solesta include injection area pain and bleeding. Infection and inflammation of anal tissue are more serious risks, but are less common.
Solesta is a registered trademark of Q-Med AB of Uppsala, Sweden; Oceana Therapeutics acquired exclusive worldwide sales and distribution rights to Solesta in June 2009. In December 2011 Salix Pharmaceuticals, Ltd. acquired all of the outstanding stock of Oceana Therapeutics, Inc.
Medical and Research News
An article published in August by several leading European gastroenterologists in the journal Alimentary Pharmacology and Therapeutics has produced a consensus report which may be helpful to doctors and their patients in deciding whether to try specific probiotics for specific lower GI symptoms.
The authors performed a systematic review of randomized, placebo-controlled clinical trials on probiotics in adults. They sought to determine the level of available evidence to support the use of specific probiotics, as a reference to physicians who could then make evidence-based recommendations to their adult patients.
They found high levels of support for a role for specific probiotics in the management of overall symptoms and abdominal pain in patients with irritable bowel syndrome (IBS), and for preventing or reducing antibiotic associated diarrhea. They found moderate evidence to support a role for specific probiotics in managing overall symptoms in patients with diarrhea prominent IBS (IBS-D); improving bowel movements and bloating/distension in patients with IBS; and improving some aspects of health-related quality of life. The authors note that these findings are specific to individual strains or formulations of probiotics and cannot be extrapolated to other products. Further studies are needed to establish similarly high levels of evidence for the role of probiotics in treating other symptoms or other functional GI disorders.
FDA Advisory Committee Will Consider Extended Use of Relistor, a Drug for Opioid-Induced Constipation
The U.S. Food and Drug Administration (FDA) will be holding an advisory committee meeting in March 2014 to review Salix’s supplemental New Drug Application, which seeks to extend the use of Relistor to include patients who are taking opioids to treat chronic pain.
Relistor was approved in the U.S. in 2008 for short-term treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care when response to laxative therapy has not been sufficient. It has also received approval for this indication in other countries.
A large scale retrospective study has shown that children with attentiondeficit/ hyperactivity disorder (ADHD) are significantly more likely to suffer from chronic constipation and bowel incontinence than kids without ADHD.
The study, published in the journal Pediatrics, looked at the medical records of more than 700,000 children. Researchers found that constipation nearly tripled and fecal incontinence increased six-fold among kids with ADHD. Children with ADHD also tended to see their doctor for their bowel problems more often, possibly suggesting that their constipation and bowel incontinence was more severe.
The study was limited to the children of active-duty military personnel. Further prospective research in the general population is needed, but parents of children with ADHD may wish to discuss these findings with their child’s doctor if they have concerns about their child’s digestive health.
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