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

Hori, Yasunobu; Imanishi, Akihito; Matsukawa, Jun; Tsukimi, Yasuhiro; Nishida, Haruyuki; Arikawa, Yasuyoshi; Hirase, Keizo; Kajino, Masahiro; Inatomi, Nobuhiro

doi:10.1124/jpet.110.170274

Cited by 183 publications

(183 citation statements)

References 35 publications

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“…Potassium‐competitive acid blockers (P‐CABs) represent a novel class of acid‐suppressing agents that are a potential alternative to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease 1. In contrast to PPIs, P‐CABs are acid‐stable H+, K+‐ATPase inhibitors that inhibit H+, K+‐ATPase noncovalently in a K+‐competitive manner 2…”

mentioning

confidence: 99%

Effect of Therapeutic and Supratherapeutic Doses of Vonoprazan on the QT/QTc Interval in a Phase I Randomized Study in Healthy Subjects

Astruc

Jenkins

2017

Clinical Translational Sci

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This phase I, randomized, 4‐period, 4‐sequence, double‐blind, active‐ and placebo‐controlled, crossover study assessed the effects of vonoprazan on the QT/QTc interval in healthy subjects. Subjects received single oral doses of vonoprazan 40 mg, vonoprazan 120 mg, moxifloxacin 400 mg (positive control/open label), and placebo. The primary end point was time‐matched, placebo‐corrected, baseline‐adjusted mean Fridericia‐corrected QT interval (ddQTcF). Of 64 subjects (mean age, 37.8 years; 50% male), 63 received all four regimens. One subject discontinued due to nondrug‐related adverse event of tonsillitis. Assay sensitivity was established; lower bound of the one‐sided 95% confidence interval (CI) for ddQTcF was >5 ms between 1.5 and 12 h following moxifloxacin administration. For both doses of vonoprazan, the one‐sided upper 95% CI ddQTcF did not exceed 10 ms. There was no correlation between plasma vonoprazan concentrations and increases in ddQTcF. Vonoprazan was well tolerated. No severe adverse events/deaths were reported. (European Clinical Trials Database Registry: 2011‐004003‐20.)

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mentioning

confidence: 99%

Effect of Therapeutic and Supratherapeutic Doses of Vonoprazan on the QT/QTc Interval in a Phase I Randomized Study in Healthy Subjects

Astruc

Jenkins

2017

Clinical Translational Sci

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“…The acid-inhibitory effect of VPZ was greater than that of the PPIs [11] [12] [32]. The CYP2C19 genotype was shown to influence the inhibitory effects of PPIs on gastric acids [31].…”

Section: Discussionmentioning

confidence: 99%

“…Vonoprazan (VPZ) is a novel orally administered member of this class. VPZ has a potent and long-lasting anti-secretory effect on hydrogen/potassium-ATPase because of its high level of accumulation and slow clearance from gastric tissue [11] [12]. The acid-inhibitory effects of VPZ are much more potent than those of PPIs; therefore, it can be expected to be more effective when used for H. pylori eradication.…”

Section: Introductionmentioning

confidence: 99%

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Gastric Mucosal Atrophy Might Be Associated with the Efficacy of First-Line Therapy Using Vonoprazan for Helicobacter pylori

Miura¹,

Ohtaka²,

Hanawa³

et al. 2017

OJGas

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Aim: To investigate the factors related to the effect of eradication therapy with vonoprazan for Helicobacter pylori (H. pylori). Methods: We retrospectively reviewed medical records of H. pylori-positive patients who received first-line (40 mg vonoprazan/60 mg lansoprazole or 20 mg rabeprazole, 1500 mg amoxicillin, 400 mg clarithromycin, all 2/day for 7 days) (n = 4118). H. pylori eradication was assessed by the 13 C-urea breath test with success defined as a result of < 2.5‰. Using propensity score matching, successful eradication rates were compared between two groups: those receiving vonoprazan and those receiving a proton pump inhibitor. Related factors and adverse events were investigated. Results: Successful first-line eradication rates according to ITT analysis and PP analysis, respectively, were 79.8% and 91.4% for VPZ therapy. Eradication rates using propensity matched patients (n = 1053) who received first-line vonoprazan therapy were higher than in those using proton pump inhibitor (PPI) therapy (92.1% vs. 79.7% in per-protocol analysis, p < 0.0001). Multivariate analysis confirmed that gastric mucosal atrophy was associated with treatment success. Conclusions: Low-dose clarithromycin triple therapy for first-line H. pylori eradication therapy using vonoprazan was more effective than standard triple therapy with proton pump inhibitor. Gastric mucosal atrophy was associated with treatment success.

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“…P-CABs inhibit gastric hydrogen/potassium-ATPase in a potassium-competitive and reversible manner [17]. Because P-CAB is highly accumulated and slowly excreted from gastric tissue, it has a potent and a long-lasting anti-secretory effect on gastric acid [18]. In Japan, triple therapy based on vonoprazan, a novel P-CAB, showed favored eradication rate compared to lansoprazole-based triple therapy [19].…”

Section: Proton Pump Inhibitormentioning

confidence: 99%

The first-line regimens of Helicobacter pylori eradication in Korea

Park

2017

Hanyang Med Rev

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Approximately half of the world's population is infected by Helicobacter pylori, which causes various gastrointestinal diseases including gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The conventional triple therapy, that consists of proton pump inhibitor (PPI), amoxicillin, and clarithromycin, is widely used in Korea because of high resistance rates of H. pylori against metronidazole. Recently, however, clarithromycin-resistance rates have also increased and the eradication rate of conventional triple therapy has been unacceptable. In order to increase the eradication rate of H. pylori, various regimens have been suggested. Understanding H. pylori eradication regimens will help select drugs in the management of H. pylori infection.

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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

Cited by 183 publications

References 35 publications

Effect of Therapeutic and Supratherapeutic Doses of Vonoprazan on the QT/QTc Interval in a Phase I Randomized Study in Healthy Subjects

Effect of Therapeutic and Supratherapeutic Doses of Vonoprazan on the QT/QTc Interval in a Phase I Randomized Study in Healthy Subjects

Gastric Mucosal Atrophy Might Be Associated with the Efficacy of First-Line Therapy Using Vonoprazan for <i>Helicobacter pylori</i>

The first-line regimens of Helicobacter pylori eradication in Korea

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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

Cited by 183 publications

References 35 publications

Effect of Therapeutic and Supratherapeutic Doses of Vonoprazan on the QT/QTc Interval in a Phase I Randomized Study in Healthy Subjects

Effect of Therapeutic and Supratherapeutic Doses of Vonoprazan on the QT/QTc Interval in a Phase I Randomized Study in Healthy Subjects

Gastric Mucosal Atrophy Might Be Associated with the Efficacy of First-Line Therapy Using Vonoprazan for &lt;i&gt;Helicobacter pylori&lt;/i&gt;

The first-line regimens of Helicobacter pylori eradication in Korea

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Gastric Mucosal Atrophy Might Be Associated with the Efficacy of First-Line Therapy Using Vonoprazan for <i>Helicobacter pylori</i>