PMID- 37666458
OWN - NLM
STAT- Publisher
LR  - 20230930
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 190
DP  - 2023 Nov 1
TI  - Keverprazan, a novel potassium-competitive acid blocker: Single ascending dose 
      safety, tolerability, pharmacokinetics, pharmacodynamics and food effect in 
      healthy subjects.
PG  - 106578
LID - S0928-0987(23)00208-7 [pii]
LID - 10.1016/j.ejps.2023.106578 [doi]
AB  - BACKGROUND: Keverprazan is a novel potassium-competitive acid blocker for the 
      treatment of acid-related diseases. AIMS: To evaluate the safety, 
      pharmacokinetics, pharmacodynamics, and food effect of single oral doses of 
      keverprazan in healthy Chinese subjects. METHODS: In the dose-escalated phase Ia 
      trial, the first 8 subjects received keverprazan 5 mg, the others successively 
      entered 10 mg, 20 mg, 40 mg, 60 mg groups and were randomized to receive 
      keverprazan (n = 8), lansoprazole (LSZ) 30 mg (n = 2) or placebo (n = 2) in each 
      dose group. The phase Ib study randomly enrolled subjects to the fasting-fed 
      (n = 7) or fed-fasting (n = 7) groups for evaluating the food effect of 
      keverprazan. RESULTS: Twenty (35.71%) adverse events (AEs) occurred in phase Ia, 
      including 13 (32.50%), 3 (37.50%), and 4 (50.00%) AEs in the keverprazan, 
      placebo, and LSZ groups, respectively. Four (28.57%) AEs occurred in Phase Ib. 
      The T(max) of keverprazan was 1.25-1.75 h. C(max) and AUC increased with the 
      dose, and the t(1/2), CL/F were 6.00-7.17 h, 88.8-198 L/h, respectively. The 
      intragastric pH >5 holding-time ratio (HTR) increased with the dose but reached a 
      ceiling at 20 mg. In the 30 mg LSZ and 5-60 mg keverprazan groups, the 
      intragastric pH >5 HTRs during 24 h were 57.1%+/-26.4%, 7.9%+/-8.1%, 26.2%+/-22.8%, 
      80.2%+/-8.8%, 88.1%+/-8.6%, and 93.0%+/-1.7%, respectively. The geometric mean ratios 
      (90% CI) of C(max) and AUC(0-infinity) of keverprazan in plasma under the fed vs. 
      fasting state were 126.8% (109.0%-147.5%) and 134.9% (123.8%-146.9%). CONCLUSION: 
      Keverprazan is tolerable, and provides significant stable and lasting inhibition 
      efficacy of intragastric acidity at 20 mg.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Zhou, Sufeng
AU  - Zhou S
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Xie, Lijun
AU  - Xie L
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Zhou, Chen
AU  - Zhou C
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Zhao, Yuqing
AU  - Zhao Y
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Wang, Lu
AU  - Wang L
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Ding, Sijia
AU  - Ding S
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Chen, Juan
AU  - Chen J
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Zhu, Bei
AU  - Zhu B
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Su, Mei
AU  - Su M
AD  - Jiangsu Carephar Pharmaceutical Co., Ltd, Nanjing 210000, China. Electronic 
      address: sumei@carephar.com.
FAU - Shao, Feng
AU  - Shao F
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing 210029, China; Department of Clinical Pharmacology, Pharmacy 
      College, Nanjing Medical University, Nanjing 211166, China. Electronic address: 
      jsphshaofeng@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20230904
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
SB  - IM
OTO - NOTNLM
OT  - Gastroesophageal reflux disease
OT  - Keverprazan
OT  - Peptic ulcer
OT  - Pharmacodynamics
OT  - Pharmacokinetics
OT  - Potassium-competitive acid blocker
COIS- Declaration of Competing Interest Mei Su is the employee of Jiangsu Carephar 
      Pharmaceutical Co., Ltd. All other authors declare that they have no competing 
      interests.
EDAT- 2023/09/05 00:42
MHDA- 2023/09/05 00:42
CRDT- 2023/09/04 19:22
PHST- 2023/04/25 00:00 [received]
PHST- 2023/07/28 00:00 [revised]
PHST- 2023/09/01 00:00 [accepted]
PHST- 2023/09/05 00:42 [pubmed]
PHST- 2023/09/05 00:42 [medline]
PHST- 2023/09/04 19:22 [entrez]
AID - S0928-0987(23)00208-7 [pii]
AID - 10.1016/j.ejps.2023.106578 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2023 Nov 1;190:106578. doi: 10.1016/j.ejps.2023.106578. Epub 
      2023 Sep 4.