Linaclotide: A new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation

United European Gastroenterology Journal

Volumn 1, Issue 1, 2013, Pages 7-20

  Corsetti, Maura ^a   Tack, Jan ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Chronic constipation; Colonic transit; Guanylate cyclase C; Irritable bowel syndrome; Linaclotide; Phase II and phase III studies; Visceral hypersensitivity

Indexed keywords

CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; CYCLIC GMP; DRUG METABOLITE; GUANYLATE CYCLASE; GUANYLIN; LINACLOTIDE; MM 419447; UNCLASSIFIED DRUG; UROGUANYLIN;

ABDOMINAL PAIN; AREA UNDER THE CURVE; ARTICLE; BLOATING; CONSTIPATION; DIARRHEA; HUMAN; HYPERSENSITIVITY; INTESTINAL SECRETION; INTESTINE MOTILITY; IRRITABLE COLON; MULTICENTER STUDY (TOPIC); PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN DEGRADATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); SYSTEMATIC REVIEW;

EID: 85006184506     PISSN: 20506406     EISSN: 20506414     Source Type: Journal    
DOI: 10.1177/2050640612474446     Document Type: Article

References (58)

1. Suares NC and Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol 2011; 106(9): 1582-1591.
2. Lembo A and Camilleri M. Chronic constipation. N Engl J Med 2003; 349(14): 1360-1368.
3. Longstreth G, Thompson W, Chey W, et al. Functional bowel disorders. Gastroenterology 2006; 130(5): 1480-1491.
4. Sun SX, Dibonaventura M, Purayidathil FW, et al. Impact of chronic constipation on health-related quality of life, work productivity, and healthcare resource use: an analysis of the National Health and Wellness Survey. Dig Dis Sci 2011; 56(9): 2688-2695.
5. Irvine EJ, Ferrazzi S, Pare P, et al. Health-related quality of life in functional GI disorders: focus on constipation and resource utilization. Am J Gastroenterol 2002; 97(8): 1986-1993.
6. Wald A and Sigurdsson L. Quality of life in children and adults with constipation. Best Pract Res Clin Gastroenterol 2011; 25(1): 19-27.
7. Dennison C, Prasad M, Lloyd A, et al. The health-related quality of life and economic burden of constipation. Pharmacoeconomics 2005; 23(5): 461-476.
8. Tack J and Mu¨ ller-Lissner S. Treatment of chronic constipation: current pharmacologic approaches and future directions. Clin Gastroenterol Hepatol 2009; 7(5): 502-508.
9. Wald A, Scarpignato C, Mueller-Lissner S, et al. A multinational survey of prevalence and patterns of laxative use among adults with self-defined constipation. Aliment Pharmacol Ther 2008; 28(7): 917-930.
10. Tack J. Current and future therapies for chronic constipation. Best Pract Res Clin Gastroenterol 2011; 25(1): 151-158.
11. American College of Gastroenterology Chronic Constipation Task Force. An evidence-based approach to the management of chronic constipation in North America. Am J Gastroenterol 2005; 100: S1-4.
12. Tack J, Müller-Lissner S, Stanghellini V, et al. Diagnosis and treatment of chronic constipation—a European perspective. Neurogastroenterol Motil 2011; 23(8): 697-710.
13. Lovell RM and Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol 2012; 10(7): 712-721.
14. Tack J, Fried M, Houghton LA, et al. Systematic review: the efficacy of treatments for irritable bowel syndrome— a European perspective. Aliment Pharmacol Ther 2006; 24(2): 183-205.
15. Johanson JF, Morton D, Geenen J, et al. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation. Am J Gastroenterol 2008; 103(1): 170-177.
16. Barish CF, Drossman D, Johanson JF, et al. Efficacy and safety of lubiprostone in patients with chronic constipation. Dig Dis Sci 2010; 55(4): 1090-1097.
17. Johanson JF, Drossman DA, Panas R, et al. Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2008; 27(8): 685-696.
18. Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome—results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther 2009; 29(3): 329-341.
19. Johnston JM, Kurtz CB, Drossman DA, et al. Pilot study on the effect of linaclotide in patients with chronic constipation. Am J Gastroenterol 2009; 104(1): 125-132.
20. Lembo AJ, Kurtz CB, Macdougall JE, et al. Efficacy of linaclotide for patients with chronic constipation. Gastroenterology 2010; 138(3): 886-895.
21. Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med 2011; 365(6): 527-536.
22. Johnston JM, Kurtz CB, Macdougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. Gastroenterology 2010; 139(6): 1877-1886.
23. Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol Epub ahead of print 18 September 2012 DOI: 10.1038/ajg.2012.255.
24. Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol Epub ahead of print 18 September 2012 DOI: 10.1038/ajg.2012.254.
25. Quigley EM, Tack J, Chey WD, et al. Randomised clinical trials: linaclotide phase 3 studies in IBS-C—a prespecified further analysis based on European Medicines Agency-specified endpoints. Aliment Pharmacol Ther 2013; 37(1): 49-61.
26. Field M, Graf LH, Laird WJ, et al. Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci USA 1978; 75(6): 2800-2804.
27. Hughes JM, Murad F, Chang B, et al. Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli. Nature 1978; 271(5647): 755-756.
28. Currie MG, Fok KF, Kato J, et al. Guanylin: an endogenous activator of intestinal guanylate cyclase. Proc Natl Acad Sci USA 1992; 89(3): 947-951.
29. Hamra FK, Forte LR, Eber SL, et al. Uroguanylin: structure and activity of a second endogenous peptide that stimulates intestinal guanylate cyclase. Proc Natl Acad Sci USA 1993; 90(22): 10464-10468.
30. Potter LR. Regulation and therapeutic targeting of peptide- activated receptor guanylyl cyclases. Pharmacol Ther 2011; 130(1): 71-82.
31. Busby RW, Bryant AP, Bartolini WP, et al. Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol 2010; 649(1-3): 328-335.
32. Bryant AP, Busby RW, Bartolini WP, et al. Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. Life Sci 2010; 86(19-20): 760-765.
33. Busby RW, Kessler MM, Bartolini WP, et al. Pharmacological properties, metabolism and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. J Pharmacol Exp Ther Epub ahead of print 22 October 2012.
34. Eutamene H, Bradesi S, Larauche M, et al. Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. Neurogastroenterol Motil 2010; 22(3): 312-e84.
35. Castro J, Harrington AM, Hugher PA, et al. Mechanism of action for linaclotide induced abdominal pain relief. Gastroenterology 2012; 142;5(Suppl 1): 699.
36. Brierley SM. Guanylate cyclase-C receptor activation: unexpected biology. Curr Opin Pharmacol 2012; 12(6): 632-640.
37. Castro J, Martin C, Hughers PA, et al. A Novel role of cyclic GMP in colonic sensory neurotransmission in Healthy and TNBS-treated mice. Gastroenterology 2011; 140(5 Suppl. 1): 538.
38. Tonini M and Pace F. Drugs acting on serotonin receptors for the treatment of functional GI disorders. Dig Dis 2006; 24(1-2): 59-69.
39. Johnston J and Schneier HA. Clarification of trial end points presented in a recent review of linaclotide. Expert Rev Gastroenterol Hepatol 2012; 6(1): 13-14.
40. Studies NCT00765999 and NCT00730171, http://www.clinicaltrials.gov/ct2/show/NCT00765999?term=linaclotide&rank=6 and http://www.clinicaltrials.gov/ct2/show/NCT00730171?term=linaclotide&rank=941. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM205269.pdf
41. Andresen V, Camilleri M, Busciglio IA, et al. Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. Gastroenterology 2007; 133(3): 761-768.
42. Trentacosti AM, He R, Burke LB, et al. Evolution of clinical trials for irritable bowel syndrome: issues in end points and study design. Am J Gastroenterol 2010; 105(4): 731-735.
43. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for industry, irritable bowel syndrome, clinical evaluation of drugs for treatment, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM205269.pdf.
44. European Medicines Agency. EMA guideline on irritable bowel syndrome (IBS). CPMP/EWP/785/97 (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003187.pdf, March 2003).
45. Camilleri M and Tack JF. Current medical treatments of dyspepsia and irritable bowel syndrome. Gastroenterol Clin North Am 2010; 39(3): 481-493.
46. Clave´ P, Acalovschi M, Triantafillidis JK, et al; OBIS Study Investigators. Randomised clinical trial: otilonium bromide improves frequency of abdominal pain, severity of distention and time to relapse in patients with irritable bowel syndrome. Aliment Pharmacol Ther 2011; 34(4): 432-442.
47. Novick J, Miner P, Krause R, et al. A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2002; 16(11): 1877-1888.
48. Nyhlin H, Bang C, Elsborg L, et al. A double-blind, placebo-controlled, randomized study to evaluate the efficacy, safety and tolerability of tegaserod in patients with irritable bowel syndrome. Scand J Gastroenterol 2004; 39(2): 119-126.
49. Johanson JF, Wald A, Tougas G, et al. Effect of tegaserod in chronic constipation: a randomized, doubleblind, controlled trial. Clin Gastroenterol Hepatol 2004; 2(9): 796-805.
50. Kamm MA, Müller-Lissner S, Talley NJ, et al. Tegaserod for the treatment of chronic constipation: a randomized, double-blind, placebo-controlled multinational study. Am J Gastroenterol 2005; 100(2): 362-372.
51. Tack J, Müller-Lissner S, Bytzer P, et al. A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation. Gut 2005; 54(12): 1707-1713.
52. Tack J, Camilleri M, Chang L, et al. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther 2012; 35(7): 745-767.
53. De Maeyer JH, Lefebvre RA and Schuurkes JA. 5-HT4 receptor agonists: similar but not the same. Neurogastroenterol Motil 2008; 20(2): 99-112.
54. Camilleri M, Kerstens R, Rykx A, et al. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med 2008; 358(22): 2344-2354.
55. Tack J, van Outryve M, Beyens G, et al. Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut 2009; 58(3): 357-365.
56. Quigley EM, Vandeplassche L, Kerstens R, et al. Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation— a 12-week, randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther 2009; 29(3): 315-328.
57. Ke M, Zou D, Yuan Y, et al. Prucalopride in the treatment of chronic constipation in patients from the Asia- Pacific region: a randomized, double-blind, placebo-controlled study. Neurogastroenterol Motil 2012; 24(11): 999-e541.
58. MacDougall JE, MacKinnon DP, Lavins BJ, et al. Mediation analysis suggests that linaclotide has a direct effect on relief of abdominal pain independent of constipation improvement. Neurogastroenterol Motil 2012; 24(Suppl. 2): 180-181.