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

Ashida, Kiyoshi; Sakurai, Yuuichi; Nishimura, Akira; Kudou, Kentarou; Hiramatsu, Naoki; Umegaki, Eiji; Iwakiri, Katsuhiko; Chiba, Tsutomu

doi:10.1111/apt.13331

Cited by 142 publications

(202 citation statements)

References 32 publications

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“…A dose of 40 mg was selected as the therapeutic dose for this study because in a previous phase II study,10 40 mg was the maximum dose used and doses ≥20 mg were expected to be used for different indications. The supratherapeutic dose in this study was 120 mg because it was the highest dose administered in healthy subjects in a phase I study4 and was well tolerated.…”

Section: Methodsmentioning

confidence: 99%

“…Electrocardiogram (ECG) parameters for vonoprazan in clinical trials have not shown any clinically meaningful QT/QTc prolongation 4, 5, 9, 10, 11, 12, 13, 14. Despite the lack of cardiac arrhythmic events in the extensive clinical development program, a thorough QT study was conducted to provide a definitive assessment of the effects of vonoprazan on the QT interval.…”

mentioning

confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

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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“…Characteristics of vonoprazan are the rapid onset, high potency, and long duration of its acid secretion-inhibitory effect 25,26 . Excellent results have also been reported by its clinical trials against reflux esophagitis 28,29 . However, there is also concern over adverse effects associated with its strong acid-suppressive effect.…”

Section: -4) Switching To Vonoprazanmentioning

confidence: 80%

Treatment Strategy for Standard-Dose Proton Pump Inhibitor-Resistant Reflux Esophagitis

Iwakiri

2017

J Nippon Med Sch

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“…In addition, the intragastric pH following VPZ treatment (pH 5.2) has been identified to be significantly higher than that following esomeprazole treatment (pH 3.0) on day 1 of therapy (18). The superior efficacy of VPZ compared with PPIs has been reported in various gastrointestinal diseases (19)(20)(21)(22).…”

Section: Eradication Rate % (N) -------------------------------------mentioning

confidence: 99%

Second‑line triple therapy in failures with vonoprazan‑based triple therapy for eradication of Helicobacter pylori

et al. 2018

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Abstract. Gastric acid inhibition during treatment is important for the eradication of Helicobacter pylori (H. pylori) infection. A novel potassium-competitive acid blocker, vonoprazan (VPZ), has been demonstrated to achieve high eradication rates; however, the efficacy of second-line treatment in failures of VPZ-based triple therapy has not been well studied.The aim of the current study was to determine the efficacy of VPZ in a first-line regimen for H. pylori eradication, and the efficacy of a second-line regimen using metronidazole (MTZ) in failures with the first-line regimen. Of 580 subjects enrolled in the study, 524 patients completed first-line treatment (275 patients who received VPZ and 249 patients who received LPZ). First-line regimens consisted of a combination of clarithromycin (CAM) 200 or 400 mg twice a day, amoxicillin (AMPC) 750 mg twice a day, and either LPZ 30 mg or VPZ 20 mg twice a day, administered orally for 7 days. CAM and VPZ/LPZ were replaced with metronidazole (MTZ) 250 mg and rabeprazole 10 mg in the second-line regimens. The eradication of H. pylori was assessed by the H. pylori stool antigen test. The overall first-line eradication rate with VPZ was significantly higher than that with LPZ [91.0% (250/275) vs. 84.7% (211/249), respectively, P=0.030]. The dose of CAM (400 vs. 800 mg) did not affect the eradication rate in either the VPZ or LPZ regimens. The overall eradication rates of the second-line regimens with MTZ did not differ significantly between the VPZ-failure and LPZ-failure groups [87.0% (20/23) vs. 87.9% (29/33), respectively, P= 0.700]. Therefore, VPZ was significantly more effective than LPZ for first-line treatment. In patients with failure of first-line eradication therapy, successful results of second-line eradication therapy did not differ between the VPZ-and LPZ-failure groups. In conclusion, VPZ-based triple therapy should be recommended for eradication of H. pylori.

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

Cited by 142 publications

References 32 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

Treatment Strategy for Standard-Dose Proton Pump Inhibitor-Resistant Reflux Esophagitis

Second‑line triple therapy in failures with vonoprazan‑based triple therapy for eradication of Helicobacter pylori

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