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      Randomised clinical trial: vonoprazan, a novel potassium‐competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis

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          Summary

          Background

          Vonoprazan is a novel potassium‐competitive acid blocker which may provide clinical benefit in acid‐related disorders.

          Aim

          To verify the non‐inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis ( EE), and to establish its long‐term safety and efficacy as maintenance therapy.

          Methods

          In this multicentre, randomised, double‐blind, parallel‐group comparison study, patients with endoscopically confirmed EE ( LA Classification Grades A–D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re‐randomised into a long‐term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks.

          Results

          Of the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long‐term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non‐inferiority of vonoprazan ( P < 0.0001). Vonoprazan was also effective in patients with more severe EE ( LA Classification Grades C/D) and CYP2C19 extensive metabolisers. In the long‐term maintenance study, there were few recurrences (<10%) of EE in patients treated with vonoprazan 10 or 20 mg. Overall, vonoprazan was well‐tolerated.

          Conclusions

          The non‐inferiority of vonoprazan to lansoprazole in EE was verified in the comparison study, and vonoprazan was well‐tolerated and effective during the long‐term maintenance study.

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          Most cited references 15

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          Epidemiology of gastro-oesophageal reflux disease: a systematic review.

          A systematic review of the epidemiology of gastro-oesophageal reflux disease (GORD) has been performed, applying strict criteria for quality of studies and the disease definition used. The prevalence and incidence of GORD was estimated from 15 studies which defined GORD as at least weekly heartburn and/or acid regurgitation and met criteria concerning sample size, response rate, and recall period. Data on factors associated with GORD were also evaluated. An approximate prevalence of 10-20% was identified for GORD, defined by at least weekly heartburn and/or acid regurgitation in the Western world while in Asia this was lower, at less than 5%. The incidence in the Western world was approximately 5 per 1000 person years. A number of potential risk factors (for example, an immediate family history and obesity) and comorbidities (for example, respiratory diseases and chest pain) associated with GORD were identified. Data reported in this systematic review can be interpreted with confidence as reflecting the epidemiology of "true" GORD. The disease is more common in the Western world than in Asia, and the low rate of incidence relative to prevalence reflects its chronicity. The small number of studies eligible for inclusion in this review highlights the need for global consensus on a symptom based definition of GORD.
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            Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk.

            When it is required to establish a materially significant difference between two treatments, or, alternatively, to show that two treatments are equivalent, standard test statistics and sample size formulae based on a null hypothesis of no difference no longer apply. This paper reviews some of the test statistics and sample size formulae proposed for comparative binomial trials when the null hypothesis is of a specified non-zero difference or non-unity relative risk. Methods based on restricted maximum likelihood estimation are recommended and applied to studies of pertussis vaccine.
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              1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases.

              Proton pump inhibitors (PPIs) are widely used in the treatment of acid-related diseases. However, several unmet medical needs, such as suppression of night-time acid secretion and rapid symptom relief, remain. In this study, we investigated the pharmacological effects of 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel potassium-competitive acid blocker (P-CAB), on gastric acid secretion in comparison with lansoprazole, a typical PPI, and SCH28080 [3-(cyanomethyl)-2-methyl,8-(phenylmethoxy)imidazo(1,2-a)pyridine], a prototype of P-CAB. TAK-438, SCH28080, and lansoprazole inhibited H(+),K(+)-ATPase activity in porcine gastric microsomes with IC(50) values of 0.019, 0.14, and 7.6 μM, respectively, at pH 6.5. The inhibitory activity of TAK-438 was unaffected by ambient pH, whereas the inhibitory activities of SCH28080 and lansoprazole were weaker at pH 7.5. The inhibition by TAK-438 and SCH28080 was reversible and achieved in a K(+)-competitive manner, quite different from that by lansoprazole. TAK-438, at a dose of 4 mg/kg (as the free base) orally, completely inhibited basal and 2-deoxy-d-glucose-stimulated gastric acid secretion in rats, and its effect on both was stronger than that of lansoprazole. TAK-438 increased the pH of gastric perfusate to a higher value than did lansoprazole or SCH28080, and the effect of TAK-438 was sustained longer than that of lansoprazole or SCH28080. These results indicate that TAK-438 exerts a more potent and longer-lasting inhibitory action on gastric acid secretion than either lansoprazole or SCH28080. TAK-438 is a novel antisecretory drug that may provide a new option for the patients with acid-related disease that is refractory to, or inadequately controlled by, treatment with PPIs.
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                Author and article information

                Journal
                Aliment Pharmacol Ther
                Aliment. Pharmacol. Ther
                10.1111/(ISSN)1365-2036
                APT
                Alimentary Pharmacology & Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                0269-2813
                1365-2036
                11 November 2015
                January 2016
                : 43
                : 2 ( doiID: 10.1111/apt.2016.43.issue-2 )
                : 240-251
                Affiliations
                [ 1 ]Rakuwakai Otowa Hospital KyotoJapan
                [ 2 ]Takeda Pharmaceutical Company Ltd. OsakaJapan
                [ 3 ]Osaka University Graduate School of Medicine OsakaJapan
                [ 4 ]Kobe University Graduate School of Medicine KobeJapan
                [ 5 ]Nippon Medical School Graduate School of Medicine TokyoJapan
                Author notes
                [* ] Correspondence to:

                Dr K. Ashida, Rakuwakai Otowa Hospital, 2 Otowachinji‐cho, Yamashina‐ku, Kyoto 607‐8062, Japan.

                E‐mail: rakuwadr1185@ 123456rakuwadr.com

                Article
                APT13461
                10.1111/apt.13461
                4738414
                26559637
                © 2015 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                Page count
                Pages: 12
                Product
                Funding
                Funded by: Takeda Pharmaceutical Company Ltd
                Award ID: TAK‐438/CCT‐002
                Award ID: TAK‐438/OCT‐001
                Categories
                Randomised Clinical Trial
                Randomised Clinical Trial
                Custom metadata
                2.0
                apt13461
                January 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.5 mode:remove_FC converted:28.01.2016

                Pharmacology & Pharmaceutical medicine

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