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Review

Drugs under development for the treatment of functional dyspepsia and related disorders

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Pages 871-889 | Received 14 Jun 2019, Accepted 24 Sep 2019, Published online: 08 Oct 2019

References

  • Stanghellini V, Talley N, Chan F, et al. Functional gastroduodenal disorders. Gastroenterology. 2016 May;150(6):1380–1392.
  • Tack J, Talley NJ. Functional dyspepsia-symptoms, definitions and validity of the Rome III criteria. Nat Rev Gastroenterol Hepatol. 2013;10:134–141.
  • Van Den Houte K, Carbone F, Tack J. Postprandial distress syndrome: stratification and management. Expert Rev Gastroenterol Hepatol. 2019 Aug;3(4):337–343.
  • Carbone F, Tack J. Gastroduodenal mechanisms underlying functional gastric disorders. Dig Dis. 2014;32(3):222–229.
  • Simrén M, Törnblom H, Palsson OS, et al. Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts. Gut. 2018 Feb;67(2):255–262.
  • Piessevaux H, de Winter B, Louis E, et al. Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings. Neurogastroenterol Motil. 2009 Apr;21(4):378–388.
  • Lacy BE, Weiser KT, Kennedy AT, et al. Functional dyspepsia: the economic impact to patients. Aliment Pharmacol Ther. 2013 Jul;38(2):170–177.
  • Tack J, Camilleri M. New developments in the treatment of gastroparesis and functional dyspepsia. Curr Opin Pharmacol. 2018 Dec;43:111–117.
  • Stanghellini V, Tack J. Gastroparesis: separate entity or just a part of dyspepsia? Gut. 2014 Dec;63(12):1972–1978.
  • Jehangir A, Parkman HP. Rome IV diagnostic questionnaire complements patient assessment of gastrointestinal symptoms for patients with gastroparesis symptoms. Dig Dis Sci. 2018 Sep;63(9):2231–2243.
  • Quigley EM, Lacy BE. Overlap of functional dyspepsia and GERD–diagnostic and treatment implications. Nat Rev Gastroenterol Hepatol. 2013 Mar;10(3):175–186.
  • Moayyedi P, Delaney BC, Vakil N, et al. The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis. Gastroenterology. 2004;127(5):1329–1337.
  • Moayyedi P, Lacy BE, Andrews CN, et al. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol. 2018 Jul;112(7):988–1013.
  • Asaoka D, Nagahara A, Hojo M, et al. Efficacy of a potassium-competitive acid blocker for improving symptoms in patients with reflux esophagitis, non-erosive reflux disease, and functional dyspepsia. Biomed Rep. 2017 Feb;6(2):175–180.
  • Masuy I, Van Oudenhove L, Tack J. Review article: treatment options for functional dyspepsia. Aliment Pharmacol Ther. 2019 May;49(9):1134–1172.
  • Pittayanon R, Yuan Y, Bollegala NP, et al. Prokinetics for functional dyspepsia. Cochrane Database Syst Rev. 2018 Oct;18(10):CD009431.
  • Pittayanon R, Yuan Y, Bollegala NP, et al. Prokinetics for functional dyspepsia: a systematic review and meta-analysis of randomized control trials. Am J Gastroenterol. 2019 Feb;114(2):233–243. .
  • Carbone F, Vandenberghe A, Holvoet L, et al. 383 - The therapeutic outcome of itopride in functional dyspepsia postprandial distress syndrome: a double-blind randomized, multicenter, placebo-controlled study. Gastroenterology. 2018;154(6):S–91.
  • Dukes GE, Scimia C, Kuo B, et al. Safety, tolerability, and pharmacodynamics of TAK-906, a dopamine 2,3 antagonist, in patients with diabetic or idiopathic gastroparesis. Neurogastroenterology and Motility. 2019 Aug;31(S3):6_abstract.
  • 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 Apr;35(7):745–767.
  • Tack J, Van Den Houte K, Carbone F. The unfulfilled promise of prokinetics for functional dyspepsia/postprandial distress syndrome. Am J Gastroenterol. 2019 Feb;114(2):204–206.
  • Mahadeva S, Ford AC. Clinical and epidemiological differences in functional dyspepsia between the East and the West. Neurogastroenterol Motil. 2016 Feb;28(2):167–174.
  • Tack J. A phase II placebo controlled randomized trial with tegaserod in functional dyspepsia patients with normal gastric emptying. Gastroenterology. 2002;122:154.
  • Vakil N, Laine L, Talley NJ, et al. Tegaserod treatment for dysmotility-like functional dyspepsia: results of two randomized, controlled trials. Am J Gastroenterol. 2008 Aug;103(8):1906–1919.
  • Carbone F, Van Den Houte K, Clevers E, et al. Prucalopride in gastroparesis: a randomized placebo-controlled crossover study. Am J Gastroenterol. 2019;114(8):1265–1274.
  • Ahn A, Barnes C, Shaywitz D, et al. Velusetrag improves gastric emptying time in subjects with diabetic or idiopathic gastroparesis. Gastroenterology. 2015;148(4):S-507 (abstract).
  • Abell T, Kuo B, Esfandyari T, et al. Velusetrag improves gastroparesis both in symptoms and gastric emptying in patients with diabetic or idiopathic gastroparesis in a 12-week global phase 2B study. Gastroenterology. 2019;156(6):S164. ( abstract).
  • Matsueda K, Hongo M, Tack J, et al. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut. 2012 Jun;61(6):821–828.
  • Altan E, Masaoka T, Farré R, et al. Acotiamide, a novel gastroprokinetic for the treatment of patients with functional dyspepsia: postprandial distress syndrome. Expert Rev Gastroenterol Hepatol. 2012 Sep;6(5):533–544.
  • Matsueda K, Hongo M, Ushijima S, et al. A long-term study of acotiamide in patients with functional dyspepsia: results from an open-label phase III trial in Japan on efficacy, safety and pattern of administration. Digestion. 2011;84(4):261–268.
  • Tack J, Pokrotnieks J, Urbonas G, et al. Long-term safety and efficacy of acotiamide in functional dyspepsia (postprandial distress syndrome)-results from the European phase 3 open-label safety trial. Neurogastroenterol Motil. 2018 Jun;30(6):e13284.
  • Van Oudenhove L, Kindt S, Vos R, et al. Influence of buspirone on gastric sensorimotor function in man. Aliment Pharmacol Ther. 2008 Dec 1;28(11–12):1326–1333.
  • Tack J, Janssen P, Masaoka T, et al. Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia. Clin Gastroenterol Hepatol. 2012 Nov;10(11):1239–1245.
  • Miwa H, Nagahara A, Tominaga K, et al. Efficacy of the 5-HT1A agonist tandospirone citrate in improving symptoms of patients with functional dyspepsia: a randomized controlled trial. Am J Gastroenterol. 2009 Nov;104(11):2779–2787.
  • Tack J, van Den Elzen B, Tytgat G, et al. A placebo-controlled trial of the 5-HT agonist R-137696 on symptoms, visceral hypersensitivity and on impaired accommodation in functional dyspepsia. Neurogastroenterol Motil. 2009 Jun;21(6):619–26, e23–4.
  • Midani D, Parkman HP. Granisetron transdermal system for treatment of symptoms of gastroparesis: a prescription registry study. J Neurogastroenterol Motil. 2016;22(4):650–655.
  • Simmons K, Parkman HP. Granisetron transdermal system improves refractory nausea and vomiting in gastroparesis. Dig Dis Sci. 2014;59(6):1231–1234.
  • Pasricha PJ, Yates KP, Sarosiek I, et al. Aprepitant has mixed effects on nausea and reduces other symptoms in patients with gastroparesis and related disorders. Gastroenterology. 2018;154(1):65–76 e11.
  • Arts J, Holvoet L, Caenepeel P, et al. Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis. Aliment Pharmacol Ther. 2007;26(9):1251–1258.
  • Friedenberg FK, Palit A, Parkman HP, et al. Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol. 2008;103(2):416–423.
  • Khoury T, Mizrahi M, Mahamid M, et al. State of the art review with literature summary on gastric peroral endoscopic pyloromyotomy for gastroparesis. J Gastroenterol Hepatol. 2018;33(11):1829–1833.
  • Camilleri M, McCallum RW, Tack J, et al. Efficacy and safety of relamorelin in diabetics with symptoms of gastroparesis: a randomized, placebo-controlled study. Gastroenterology. 2017;153(5):1240–50 e2.
  • Barton ME, Otiker T, Johnson LV, et al. A randomized, double-blind, placebo-controlled phase ii study (mot114479) to evaluate the safety and efficacy and dose response of 28 days of orally administered camicinal, a motilin receptor agonist, in diabetics with gastroparesis. Gastroenterology. 2014;146(5):S20.
  • Agarwal S, Gowda KV, Mandal U, et al. Bioequivalence study of a sustained release fixed dose combination capsule containing esomeprazole and domperidone in healthy subjects. Arzneimittelforschung. 2007;57(5):274–277.
  • Choi HY, Noh YH, Jin SJ, et al. Bioavailability and tolerability of combination treatment with revaprazan 200 mg + itopride 150 mg: a randomized crossover study in healthy male Korean volunteers. Clin Ther. 2012 Sep;34(9):1999–2010.
  • Jung HK, Lee KJ, Choi MG, et al. Efficacy of DA-9701 (Motilitone) in functional dyspepsia compared to pantoprazole: a multicenter, randomized, double-blind, non-inferiority study. J Neurogastroenterol Motil. 2016 Apr 30;22(2):254–263.
  • Hojo M, Nagahara A, Asaoka D, et al. A randomized, double-blind, pilot study of the effect of famotidine on acotiamide treatment for functional dyspepsia. Digestion. 2017;96(1):5–12.
  • Drossman DA, Tack J, Ford AC, et al. Neuromodulators for functional gastrointestinal disorders (disorders of Gut-brain interaction): a Rome foundation working team report. Gastroenterology. 2018;154(4):1140–1171.e1141.
  • Talley NJ, Locke GR, Saito YA, et al. Effect of amitriptyline and escitalopram on functional dyspepsia: a multicenter, randomized controlled study. Gastroenterology. 2015;149(2):340–349.e342.
  • Lacy B, Saito Y, Camilleri M, et al. Effects of antidepressants on gastric function in patients with functional dyspepsia. Am J Gastroenterol. 2018;113:216–224.
  • van Kerkhoven LA, Laheij RJ, Aparicio N, et al. Effect of the antidepressant venlafaxine in functional dyspepsia: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2008;6(7):746–775.
  • Tack J, Ly HG, Carbone F, et al. Efficacy of mirtazapine in patients with functional dyspepsia and weight loss. Clin Gastroenterol Hepatol. 2016;14(3):385–392.e384.
  • Carbone F, Vanuytsel T, Tack J. The effect of mirtazapine on gastric accommodation, gastric sensitivity to distention, and nutrient tolerance in healthy subjects. Neurogastroenterol Motil. 2017;29:12.
  • Kessler M, Solinga R, Zimmer D, et al. IW-9179, a phosphopeptide designed to target the upper gastrointestinal tract, is more potent at acidic pH and is rapidly metabolized in vitro in rodent intestinal fluid. Gastroenterology. 2015;148(4, Supplement 1):S–823. ( abstract).
  • Tack J, Fitch D, Shao J, et al. Evaluation of daily GI symptoms in a phase 2a study of IW-9179 in functional dyspepsia (abstract #P1637). Am J Gastroenterol. 2014;109:S637–S638.
  • Ironwood press release. [cited 2019 June 1]. https://investor.ironwoodpharma.com/default.aspx?SectionId=5cc5ecae-6c48-4521-a1ad-480e593e4835&LanguageId=1&PressReleaseId=7b388bfc-3d82-4f4a-8620-a802008a95ce
  • Ly HG, Ceccarini J, Weltens N, et al. Increased cerebral cannabinoid-1 receptor availability is a stable feature of functional dyspepsia: a [F]MK-9470 PET study. Psychother Psychosom. 2015;84(3):149–158.
  • Ameloot K, Janssen P, Scarpellini E, et al. Endocannabinoid control of gastric sensorimotor function in man. Aliment Pharmacol Ther. 2010 May;31(10):1123–1131.
  • Higgins P, Ginsburg D, Gilder K, et al. P418 safety and efficacy of olorinab, a peripherally restricted, highly-selective, cannabinoid receptor 2 agonist in a phase 2A study in chronic abdominal pain associated with Crohn’s disease. ECCO. 2019;P418.
  • Sugano K, Tack J, Kuipers EJ, et al. faculty members of kyoto global consensus conference. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64:1353–1367.
  • Zhong L, Shanahan ER, Raj A, et al. Dyspepsia and the microbiome: time to focus on the small intestine. Gut. 2017 Jun;66(6):1168–1169.
  • Igarashi M, Nakae H, Matsuoka T, et al. Alteration in the gastric microbiota and its restoration by probiotics in patients with functional dyspepsia. BMJ Open Gastro. 2017;3:e000144.
  • Tan VP, Liu KS, Lam FY, et al. Randomised clinical trial: rifaximin versus placebo for the treatment of functional dyspepsia. Aliment Pharmacol Ther. 2017 Mar;45(6):767–776.
  • Melzer J, Rösch W, Reichling J, et al. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther. 2004 Dec;20(11–12):1279–1287.
  • May B, Kohler S, Schneider B. Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia. Aliment Pharmacol Ther. 2000;14(12):1671–1677.
  • Rich G, Shah A, Koloski N, et al. A randomized placebo-controlled trial on the effects of Menthacarin, a proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of life in patients with functional dyspepsia. Neurogastroenterol Motil. 2017 Nov;29(11):e13132.
  • Chey WD, Lacy BE, Cash BD, et al. Sa1619 - Efficacy of caraway oil/l-menthol plus usual care vs placebo plus usual care, in functional dyspepsia patients with Post-Prandial Distress (PDS) or Epigastric Pain (EPS) Syndromes: results from a us RCT. Gastroenterology. 2017;152(5):S307(abstract).
  • Papathanasopoulos A, Rotondo A, Janssen P, et al. Effect of acute peppermint oil administration on gastric sensorimotor function and nutrient tolerance in health. Neurogastroenterol Motil. 2013;25(4):e263–271.
  • Micklefield G, Jung O, Greving I, et al. Effects of intraduodenal application of peppermint oil (WS(R) 1340) and caraway oil (WS(R) 1520) on gastroduodenal motility in healthy volunteers. Phytother Res. 2003;17(2):135–140.
  • Suzuki H, Matsuzaki J, Fukushima Y, Rikkunshito study group, et al. Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia–a multicenter, double-blind, randomized, placebo-controlled study. Neurogastroenterol Motil. 2014 Jul;26(7):950–961.
  • Tominaga K, Sakata Y, Kusunoki H, et al. Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: a randomized clinical trial (the DREAM study). Neurogastroenterol Motil. 2018 Jul;30(7):e13319.
  • Togawa K, Matsuzaki J, Kobayakawa M, et al. Association of baseline plasma des-acyl ghrelin level with the response to rikkunshito in patients with functional dyspepsia. J Gastroenterol Hepatol. 2016;31(2):334–341.
  • Jaafar MH, Safi SZ, Tan MP, et al. Efficacy of rebamipide in organic and functional dyspepsia: a systematic review and meta-analysis. Dig Dis Sci. 2018 May;63(5):1250–1260.
  • Potter MDE, Wood NK, Walker MM, et al. Proton pump inhibitors and suppression of duodenal eosinophilia in functional dyspepsia. Gut. 2018. gutjnl-2018-316878. DOI:10.1136/gutjnl-2018-316878.
  • Wauters L, Ceulemans M, Lambaerts M, et al. Duodenal hyperpermeability, eosinophilia and symptoms in functional dyspepsia patients are reduced by proton pump inhibitors. Neurogastroetnerol and motil.2019;31(S4):126_abstract.
  • Potter MDE, Goodsall TM, Walker MM, et al. Dual histamine blockade for the treatment of adult functional dyspepsia: a single centre experience. Gut. 2019. pii:gutjnl-2019-318412. DOI:10.1136/gutjnl-2019-318412. (Epub ahead of print).
  • Friesen CA, Kearns GL, Andre L, et al. Clinical efficacy and pharmacokinetics of montelukast in dyspeptic children with duodenal eosinophilia. J Pediatr Gastroenterol Nutr. 2004;38:343–351.
  • Friesen CA, Sandridge L, Andre L, et al. Mucosal eosinophilia and response to H1/H2 antagonist and cromolyn therapy in pediatric dyspepsia. Clin Pediatr (Phila). 2006;45:143–147.
  • Palsson OS, Van Tilburg MAI, Sperber A, et al. Rome IV diagnostic questionnaires and tables for investigators and clinicians. Gastroenterology. 2016 May;150(6):1481–1491.
  • Aziz I, Palsson OS, Törnblom H, et al. Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study. Lancet Gastroenterol Hepatol. 2018 Apr; 3(4):252–262.
  • Van Den Houte K, Carbone F, Pannemans J, et al. Prevalence and impact of self-reported irritable bowel symptoms in the general population. United Eur Gastroenterol J. 2019 Mar;7(2):307–315.
  • Pleyer C, Bittner H, Locke GR 3rd, et al. Overdiagnosis of gastro-esophageal reflux disease and underdiagnosis of functional dyspepsia in a USA community. Neurogastroenterol Motil. 2014;26:1163–1171.
  • Corinaldesi R, Stanghellini V, Raiti C, et al. Effect of chronic administration of cisapride on gastric emptying of a solid meal and on dyspeptic symptoms in patients with idiopathic gastroparesis. Gut. 1987 Mar;28(3):300–305.
  • Richards RD, Valenzuela GA, Davenport KG, et al. Objective and subjective results of a randomized, double-blind, placebo-controlled trial using cisapride to treat gastroparesis. Dig Dis Sci. 1993 May;38(5):811–816.
  • U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patient‐reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes. 2006;4:79.
  • Janssen P, Harris MS, Jones M, et al. The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis. Am J Gastroenterol. 2013 Sep;108(9):1382–1391.
  • [cited 2019 June 1]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/gastroparesis-clinical-evaluation-drugs-treatment.
  • Parkman HP, Yates K, Hasler WL, et al. Clinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity. Gastroenterology. 2011;140:101–115.
  • Revicki DA, Speck RM, Lavoie S, et al. The American neurogastroenterology and motility society gastroparesis cardinal symptom index-daily diary (ANMS GCSI-DD): psychometric evaluation in patients with idiopathic or diabetic gastroparesis. Neurogastroenterol Motil. 2019 Apr;31(4):e13553.
  • Carbone F, Vandenberghe A, Holvoet L, et al. Validation of the leuven postprandial distress scale, a questionnaire for symptom assessment in the functional dyspepsia/postprandial distress syndrome. Aliment Pharmacol Ther. 2016 Nov;44(9):989–1001.
  • Taylor F, Higgins S, Carson RT, et al. Patient-reported outcome consortiumʼs functional dyspepsia working group. Development of a symptom-focused patient-reported outcome measure for functional dyspepsia: the Functional Dyspepsia Symptom Diary (FDSD). Am J Gastroenterol. 2018 Jan;113(1):39–48.
  • Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology. 2006 Apr;130(5):1466–1479.
  • Carbone F, Holvoet L, Tack J. Rome III functional dyspepsia subdivision in PDS and EPS: recognizing postprandial symptoms reduces overlap. Neurogastroenterol Motil. 2015;27:1069–1074.

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