# Prucalopride, Investigational Drug,Evaluated In Chronic Constipation



## Jeffrey Roberts (Apr 15, 1987)

http://www.jnj.com/news_finance/195.htm Evaluated In Chronic Constipation San Diego, CA (May 21, 2000) -- New studies regarding prucalopride, an investigational drug being developed by the Janssen Research Foundation, are being presented here at the annual Digestive Disease Week (DDW) meeting. They follow previous data on prucaloprideï¿½s potential use in the treatment of chronic constipation,1 a widespread condition affecting as many as 30 million individuals in the United States alone.2 Prucalopride is a novel, selective and specific serotonin (5HT4) receptor agonist that belongs to a new class of medications known as the benzofurancarboxamides. The studies presented at DDW report that prucalopride may increase the frequency of bowel movements and improve colonic transit (the time it takes for food to move through the colon), both of which are key factors in the effective treatment of chronic constipation. The findings are significant because current therapies for chronic constipation are  inadequate or poorly tolerated in many patients.3 ï¿½These new findings build upon the value of prucalopride in treating chronic constipation,ï¿½ says Alan Joslyn, PhD, executive director of global clinical research and development in gastroenterology for the Janssen Research Foundation located in Titusville, NJ, and Beerse, Belgium. ï¿½These data contribute greatly to our understanding of prucalopride and how it may benefit patients.ï¿½ Two New Studies Show Effect on Symptoms One abstract presented at the meeting summarized results of two multi-center, randomized, double-blind, placebo-controlled studies, which together included 1,261 patients. Using patient diaries and questionnaires, the studies measured the effects of prucalopride on bowel-movement frequency and stool consistency, and on other patient complaints associated with chronic constipation, such as abdominal symptoms (e.g.; pain, discomfort, cramping and bloating) and straining during defecation.4 The studies found that compared to patients taking placebo, study participants taking prucalopride (either 2 mg or 4 mg once daily) experienced a significantly greater (p < .003) increase in their average number of bowel movements that were not laxative-induced and that provided a complete sense of evacuation.5 When they entered the studies, more than 60 percent of the patients classified themselves as having severe or very severe constipation. More than half of the subjects had zero bowel movements per week that were both spontaneous (non-laxative induced) and complete (patients felt they had completely evacuated their bowels).6 During the 12 weeks of the studies, 29 percent of the patients taking prucalopride had three or more spontaneous, complete bowel movements per week. In contrast, fewer than 13 percent of individuals receiving placebo experienced such an improvement.7 In addition, prucalopride showed a statistically significant difference from placebo in reducing the percent of bowel movements associated with severe/very severe straining (p < .006) and with stools that were hard or  very hard (p < .015).8 Furthermore, the subjectsï¿½ overall assessment of severity improved.9 Prucalopride was well tolerated in the two twelve-week studies. The most common adverse events occurring in >10 percent of individuals receiving either treatment or placebo in both studies were headache, abdominal pain, nausea, diarrhea and flatulence. The majority of these side effects were mild to moderate in severity and transient in nature.10 Three other randomized, placebo-controlled studies also suggested potential benefits of prucalopride. One study of 40 patients diagnosed with chronic constipation or constipation-predominant irritable bowel syndrome suggested that prucalopride may significantly accelerate gastric emptying and emptying of the small bowel and ascending colon.11 Another study indicated that in 73 female patients, prucalopride significantly improved stool frequency (p = .008) and decreased the straining (p = .06) associated with bowel movements. In this study, prucalopride also hastened the movement of food through the upper gut and colon in individuals who have slow transit.12 A third study supported these benefits and suggested that prucalopride may reduce colonic transit time in patients with chronic constipation.13 Janssen is investigating other potential therapeutic applications of prucalopride, including the treatment of constipation-predominant irritable bowel syndrome, opioid-induced constipation, and functional constipation in children. Janssen will continue to conduct studies to determine the drugï¿½s minimally effective dose. The Janssen Research Foundation, a global organization that is part of the Johnson & Johnson Family of Companies, conducts pharmaceutical research and development and achieves regulatory approval for prescription drug products in areas such as analgesia, gastroenterology, neurology, oncology and psychiatry. It operates from two central locations in Beerse, Belgium and Titusville, NJ. References (1) Miner PB Jr, Nichols T, Silvers DR,  Joslyn A, Woods M, et al. The efficacy and safety of prucalopride in patients with chronic constipation. Gastroenterology. 1999; 116 (4; part 2), p. A1043). (2) Stewart WF, Liberman JN, Sandler RS, et al. Epidemiology of constipation (EPOC) study in the United States: Relations of clinical subtypes to sociodemographic features. Am J Gastroenterol. 1999:94 (12): 3530-40. (3) Emmanuel AV, Nicholls T, Roy AJ, Antonelli K, Kamm MA. Prucalopride improves colonic transit and stool frequency in patients with slow and normal transit constipation. Gastroenterology. 2000; 118 (4), A 846. (4) Johanson JR, Miner PB Jr, Parkman HP, et al. Prucalopride improves bowel movement frequency and symptoms in patients with chronic constipation: results of two double-blind, placebo-controlled trials. Gastroenterology 2000; 118(4), A175. (5) Johanson, JR, Miner PB Jr, Parkman HP, et al. (6) Johanson, JR, Miner PB Jr, Parkman HP, et al. (7) Johanson, JR, Miner PB Jr, Parkman HP, et al. (8) Johanson, JR, Miner PB Jr, Parkman HP, et al. (9) Johanson JR, Miner PB Jr, Parkman HP, et al. (10) Data on file, Janssen Research Foundation. (11) Camilleri M, McKinzie S, Burton, D, et al. Prucalopride accelerates small bowel and colonic transit in patients with chronic functional constipation or constipation predominant irritable bowel syndrome. Gastroenterology. 2000; 118 (4), A845. (12) Emmanuel, AV, et al. (13) Sloots CEJ, Poen AC, Felt-Bersma, RJF, et al. Effects of prucalopride on colonic transit in patients with chronic constipation. Gastroenterology 2000; 118(4), A847. # # #


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