Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: A randomised controlled trial

Gut

Volumn 62, Issue 9, 2013, Pages 1248-1255

  Shaheen, Nicholas J ^a   Denison, Hans ^b   Björck, Karin ^b   Karlsson, Maria ^b   Silberg, Debra G ^c  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b ASTRAZENECA R AND D   (Sweden)

^c ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ESOMEPRAZOLE; LANSOPRAZOLE; LESOGABERAN; OMEPRAZOLE; PANTOPRAZOLE; PLACEBO; PROTON PUMP INHIBITOR; RABEPRAZOLE;

ADD ON THERAPY; ADULT; AGED; ARTICLE; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FAINTNESS; FEMALE; GASTROESOPHAGEAL REFLUX; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; ORTHOSTATIC BLOOD PRESSURE; PARESTHESIA; PHASE 2 CLINICAL TRIAL; PRESYNCOPE; PRIORITY JOURNAL; PRURITUS; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL; REFLUX SYMPTOM QUESTIONNAIRE; SIDE EFFECT;

BARRETTS CARCINOMA; BARRETTS METAPLASIA; BARRETTS OESOPHAGUS; GABAB RECEPTOR AGONISTS; GASTRO-OESOPHAGEAL REFLUX; GASTRO-OESOPHAGEAL REFLUX DISEASE; GASTROINTESTINAL ENDOSCOPY; LESOGABERAN; PROTON PUMP INHIBITORS;

ADULT; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG MONITORING; DRUG THERAPY, COMBINATION; ESOPHAGEAL SPHINCTER, LOWER; FEMALE; GABA-A RECEPTOR AGONISTS; GASTROESOPHAGEAL REFLUX; HUMANS; MALE; MIDDLE AGED; PHOSPHINIC ACIDS; PROPYLAMINES; PROTON PUMP INHIBITORS; TREATMENT OUTCOME;

EID: 84881547705     PISSN: 00175749     EISSN: 14683288     Source Type: Journal    
DOI: 10.1136/gutjnl-2012-302737     Document Type: Article

References (24)

1. Dent J, El-Serag HB, Wallander MA, et al. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2005;54:710-17. (Pubitemid 40559260)
2. Tack J. Recent developments in the pathophysiology and therapy of gastroesophageal reflux disease and nonerosive reflux disease. Curr Opin Gastroenterol 2005;21:454-60. (Pubitemid 40961174)
3. El-Serag H, Becher A, Jones R. Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies. Aliment Pharmacol Ther 2010;32:720-37.
4. Fass R. Proton-pump inhibitor therapy in patients with gastro-oesophageal reflux disease: putative mechanisms of failure. Drugs 2007;67:1521-30. (Pubitemid 47267295)
5. Jones R, Liker HR, Ducrotté P. Relationship between symptoms, subjective well-being and medication use in gastro-oesophageal reflux disease. Int J Clin Pract 2007;61:1301-7. (Pubitemid 47052376)
6. Boeckxstaens GE, Smout A. Systematic review: role of acid, weakly acidic and weakly alkaline reflux in gastroesophageal reflux disease. Aliment Pharmacol Ther 2010;32:334-43.
7. Dent J, Holloway RH, Toouli J, et al. Mechanisms of lower oesophageal sphincter incompetence in patients with symptomatic gastrooesophageal reflux. Gut 1988;29:1020-8.
8. Holloway RH, Dent J. Pathophysiology of gastroesophageal reflux. Lower esophageal sphincter dysfunction in gastroesophageal reflux disease. Gastroenterol Clin North Am 1990;19:517-35. (Pubitemid 20337439)
9. Blackshaw LA. Receptors and transmission in the brain-gut axis: potential for novel therapies. IV. GABA(B) receptors in the brain-gastroesophageal axis. Am J Physiol Gastrointest Liver Physiol 2001;281:G311-15.
10. Lidums I, Lehmann A, Checklin H, et al. Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. Gastroenterology 2000;118:7-13. (Pubitemid 30020367)
11. Vela MF, Tutuian R, Katz PO, et al. Baclofen decreases acid and non-acid post-prandial gastro-oesophageal reflux measured by combined multichannel intraluminal impedance and pH. Aliment Pharmacol Ther 2003;17:243-51. (Pubitemid 36174255)
12. Zhang Q, Lehmann A, Rigda R, et al. Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease. Gut 2002;50:19-24. (Pubitemid 34028297)
13. Koek GH, Sifrim D, Lerut T, et al. Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors. Gut 2003;52:1397-402. (Pubitemid 37176716)
14. Lehmann A, Antonsson M, Holmberg AA, et al. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABA(B) receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action. J Pharmacol Exp Ther 2009;331:504-12.
15. Boeckxstaens GE, Beaumont H, Mertens V, et al. Effects of lesogaberan on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease. Gastroenterology 2010;139:409-17.
16. Boeckxstaens GE, Rydholm H, Lei A, et al. Effect of lesogaberan, a novel GABA (B)-receptor agonist, on transient lower esophageal sphincter relaxations in male subjects. Aliment Pharmacol Ther 2010;31:1208-17.
17. Boeckxstaens GE, Beaumont H, Hatlebakk JG, et al. A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial. Gut 2011;60:1182-8.
18. Vakil N, Karlsson M, Denison H, et al. A patient reported outcome instrument in partial responders to proton pump inhibitor therapy suggests new symptoms deserve consideration: results of a validation study. Gut 2011;60(Suppl 3):A266.
19. Moher D, Hopewell S, Schulz KF, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c869.
20. Vakil N, Björck K, Denison H, et al. Validation of the Reflux Symptom Questionnaire Electronic Diary in partial responders to proton pump inhibitor therapy. Clin Transl Gastroenterol 2012;3:e7. doi:10.1038/ctg.2012.1
21. Quigley EM. Non-erosive reflux disease, functional heartburn and gastroesophageal reflux disease; insights into pathophysiology and clinical presentation. Chin J Dig Dis 2006;7:186-90.
22. Zerbib F, Roman S, Ropert A, et al. Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy. Am J Gastroenterol 2006;101:1956-63. (Pubitemid 44337616)
23. Vakil NB, Huff FJ, Bian A, et al. Arbaclofen placarbil in GERD: a randomized, double-blind, placebo-controlled study. Am J Gastroenterol 2011;106:1427-38.
24. Castell DO, Zerbib F, Bruley des Varnnes S, et al. Efficacy and tolerability of ADX10059, a mGluR5 negative allosteric modulator, as add on therapy to proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Gastroenterology 2011;140(Suppl 1):S-557 [abstract Mo1185].