PMID- 37533172
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231023
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 16
IP  - 10
DP  - 2023 Oct
TI  - Keverprazan, a novel potassium-competitive acid blocker: Multiple oral doses 
      safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects.
PG  - 1911-1922
LID - 10.1111/cts.13598 [doi]
AB  - Keverprazan, a novel potassium-competitive acid blocker, was approved for 
      treating acid-related diseases. This study aimed to analyze the safety, 
      pharmacokinetics (PKs) and pharmacodynamics (PDs) of multiple doses of 
      keverprazan. This was a randomized, positive-/placebo-controlled, phase Ic trial. 
      Twenty-six healthy adults were randomized to receive 20 mg/day keverprazan 
      (n = 8), 40 mg/day keverprazan (n = 8), placebo (n = 6), or 20 mg/day vonoprazan 
      (n = 4) for 7 days. Safety, PK and PD assessments were conducted. In the 
      keverprazan, vonoprazan, and placebo groups, adverse events (AEs) were reported 
      in nine (56.25%), two (50.00%), and three (50.00%) subjects, respectively. AEs 
      were mild except a moderate abdominal pain leading to withdraw. No serious AEs 
      occurred. The plasma concentration-time profiles of keverprazan showed rapid 
      absorption (median time to maximum plasma concentration of 1.25-3.0 h). The 
      terminal half-life was 6.23 and 7.01 h for keverprazan 20 and 40 mg groups on day 
      7. The maximum plasma concentration was 43.1 and 93.2 ng/mL, respectively. There 
      was no apparent accumulation of keverprazan and the major metabolite after 7-day 
      administration. The intragastric pH greater than 5 holding time ratios (HTRs) 
      over 24 h postdose increased from 79.1%, 84.4%, and 84.5% on day 1 to 99.0%, 
      97.4%, and 100.0% on day 7 in the vonoprazan 20 mg and keverprazan 20 and 40 mg 
      groups, respectively. The intragastric pH greater than 5 HTR of keverprazan 
      reached a plateau at 20 mg. Keverprazan is well-tolerable. A steady-state in 
      exposure was generally reached after 7 days of treatment. A dose of 20 mg/day 
      keverprazan can elicit a significant, stable, and long-lasting gastric acid 
      inhibition effect.
CI  - (c) 2023 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Zhou, Sufeng
AU  - Zhou S
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing, China.
FAU - Xie, Lijun
AU  - Xie L
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing, China.
FAU - Zhou, Chen
AU  - Zhou C
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing, China.
FAU - Wang, Lu
AU  - Wang L
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing, China.
FAU - Chen, Juan
AU  - Chen J
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing, China.
FAU - Ding, Sijia
AU  - Ding S
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing, China.
FAU - Zhu, Bei
AU  - Zhu B
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing, China.
FAU - Su, Mei
AU  - Su M
AD  - Jiangsu Carephar Pharmaceutical Co., Ltd., Nanjing, China.
FAU - Shao, Feng
AU  - Shao F
AUID- ORCID: 0000-0001-8861-7299
AD  - Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical 
      University, Nanjing, China.
AD  - Department of Clinical Pharmacology, Pharmacy College, Nanjing Medical 
      University, Nanjing, China.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230802
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 
      (1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Healthy Volunteers
MH  - *Potassium
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Administration, Oral
PMC - PMC10582672
COIS- M.S. is the employee of Jiangsu Carephar Pharmaceutical Co., Ltd. All other 
      authors declared no competing interests for this work.
EDAT- 2023/08/03 06:42
MHDA- 2023/10/23 12:43
PMCR- 2023/08/02
CRDT- 2023/08/03 00:43
PHST- 2023/06/20 00:00 [revised]
PHST- 2023/04/19 00:00 [received]
PHST- 2023/07/13 00:00 [accepted]
PHST- 2023/10/23 12:43 [medline]
PHST- 2023/08/03 06:42 [pubmed]
PHST- 2023/08/03 00:43 [entrez]
PHST- 2023/08/02 00:00 [pmc-release]
AID - CTS13598 [pii]
AID - 10.1111/cts.13598 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2023 Oct;16(10):1911-1922. doi: 10.1111/cts.13598. Epub 2023 Aug 
      2.