PMID- 32779057
OWN - NLM
STAT- MEDLINE
DCOM- 20210824
LR  - 20210824
IS  - 1437-7799 (Electronic)
IS  - 1342-1751 (Print)
IS  - 1342-1751 (Linking)
VI  - 24
IP  - 12
DP  - 2020 Dec
TI  - Correction of serum potassium with sodium zirconium cyclosilicate in Japanese 
      patients with hyperkalemia: a randomized, dose-response, phase 2/3 study.
PG  - 1144-1153
LID - 10.1007/s10157-020-01937-1 [doi]
AB  - BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an oral potassium binder 
      approved to treat hyperkalemia in adults in a number of countries, including 
      Japan. METHODS: This phase 2/3, randomized, double-blind, placebo-controlled, 
      dose-response study (ClinicalTrials.gov: NCT03127644) was designed to determine 
      the efficacy and safety of SZC in Japanese adults with hyperkalemia. Patients 
      with serum potassium (sK(+)) concentrations >/= 5.1- </= 6.5 mmol/L were randomized 
      1:1:1 to SZC 5 g, SZC 10 g, or placebo three times daily for 48 h (six doses 
      total). The primary efficacy endpoint was the exponential rate of change in sK(+) 
      over 48 h. The proportion of patients with normokalemia (sK(+) 3.5-5.0 mmol/L) at 
      48 h and adverse events (AEs) were also evaluated. RESULTS: Overall, 103 patients 
      (mean age, 73.2 years; range 50-89 years) received SZC 5 g (n = 34), SZC 10 g 
      (n = 36), or placebo (n = 33). The exponential rate of sK(+) change from 0 to 
      48 h versus placebo was - 0.00261 (SZC 5 g) and - 0.00496 (SZC 10 g; both 
      P < 0.0001). At 48 h, the proportions of patients with normokalemia were 85.3%, 
      91.7%, and 15.2% with SZC 5 g, SZC 10 g, and placebo, respectively. No serious 
      AEs were reported. Hypokalemia (sK(+)  < 3.5 mmol/L) occurred in two patients in 
      the SZC 10 g group; normokalemia was re-established within 6 days and no 
      treatment-related AEs were reported. CONCLUSION: SZC is effective and well 
      tolerated in Japanese patients with hyperkalemia.
FAU - Kashihara, Naoki
AU  - Kashihara N
AD  - Department of Nephrology and Hypertension, Kawasaki Medical School, Okayama, 
      Japan.
FAU - Nishio, Toshiki
AU  - Nishio T
AD  - Nephrology Dialysis Center, Kusatsu General Hospital, Shiga, Japan.
FAU - Osonoi, Takeshi
AU  - Osonoi T
AD  - Department of Internal Medicine, Nakakinen Clinic, Ibaraki, Japan.
FAU - Saka, Yosuke
AU  - Saka Y
AD  - Department of Nephrology, Kasugai Municipal Hospital, Aichi, Japan.
FAU - Imasawa, Toshiyuki
AU  - Imasawa T
AD  - Department of Nephrology, Chiba-Higashi Hospital, Chiba, Japan.
FAU - Ohtake, Takayasu
AU  - Ohtake T
AD  - Department of Nephrology, Shonan Kamakura General Hospital, Kanagawa, Japan.
FAU - Mizuno, Hiroshi
AU  - Mizuno H
AD  - Department of Nephrology, Inage Hospital, Chiba, Japan.
FAU - Shibagaki, Yugo
AU  - Shibagaki Y
AD  - Division of Nephrology and Hypertension, St. Marianna University School of 
      Medicine Hospital, Kanagawa, Japan.
FAU - Kim, Hyosung
AU  - Kim H
AD  - Research and Development, AstraZeneca K.K, 1-8-3, Marunouchi, Chiyoda-ku, Tokyo, 
      100-0005, Japan.
FAU - Yajima, Toshitaka
AU  - Yajima T
AD  - Research and Development, AstraZeneca K.K, 1-8-3, Marunouchi, Chiyoda-ku, Tokyo, 
      100-0005, Japan.
FAU - Sarai, Nobuaki
AU  - Sarai N
AUID- ORCID: 0000-0002-7525-6102
AD  - Research and Development, AstraZeneca K.K, 1-8-3, Marunouchi, Chiyoda-ku, Tokyo, 
      100-0005, Japan. nobuaki.sarai@astrazeneca.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT03127644
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20200810
PL  - Japan
TA  - Clin Exp Nephrol
JT  - Clinical and experimental nephrology
JID - 9709923
RN  - 0 (Biomarkers)
RN  - 0 (Chelating Agents)
RN  - 0 (Silicates)
RN  - D652ZWF066 (sodium zirconium cyclosilicate)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/blood
MH  - Chelating Agents/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hyperkalemia/blood/diagnosis/*drug therapy
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Potassium/*blood
MH  - Silicates/adverse effects/*therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC7599176
OTO - NOTNLM
OT  - Hyperkalemia
OT  - Japan
OT  - Japanese
OT  - Sodium zirconium cyclosilicate
COIS- N Kashihara has received consulting fees from AstraZeneca and has received 
      research grants from AstraZeneca and the Japan Agency for Medical Research and 
      Development. Y Saka, T Nishio, T Osonoi, T Imasawa, T Ohtake, H Mizuno, and Y 
      Shibagaki have no conflicts of interest to disclose. H Kim, T Yajima, and N Sarai 
      are employees of AstraZeneca K.K.
EDAT- 2020/08/12 06:00
MHDA- 2021/08/25 06:00
PMCR- 2020/08/10
CRDT- 2020/08/12 06:00
PHST- 2020/04/29 00:00 [received]
PHST- 2020/07/19 00:00 [accepted]
PHST- 2020/08/12 06:00 [pubmed]
PHST- 2021/08/25 06:00 [medline]
PHST- 2020/08/12 06:00 [entrez]
PHST- 2020/08/10 00:00 [pmc-release]
AID - 10.1007/s10157-020-01937-1 [pii]
AID - 1937 [pii]
AID - 10.1007/s10157-020-01937-1 [doi]
PST - ppublish
SO  - Clin Exp Nephrol. 2020 Dec;24(12):1144-1153. doi: 10.1007/s10157-020-01937-1. 
      Epub 2020 Aug 10.