PMID- 30240132
OWN - NLM
STAT- MEDLINE
DCOM- 20200713
LR  - 20200713
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Print)
IS  - 2160-763X (Linking)
VI  - 8
IP  - 5
DP  - 2019 Jul
TI  - Pharmacokinetics and Safety of CSL112 (Apolipoprotein A-I [Human]) in Adults With 
      Moderate Renal Impairment and Normal Renal Function.
PG  - 628-636
LID - 10.1002/cpdd.618 [doi]
AB  - CSL112 (Apolipoprotein A-I [human]) is an intravenous preparation of 
      apolipoprotein A-I (apoA-I), formulated with phosphatidylcholine (PC) and 
      stabilized with sucrose, in development to prevent early recurrent cardiovascular 
      events following acute myocardial infarction (AMI). This phase 1 study was 
      designed to determine if moderate renal impairment (RI) influenced the 
      pharmacokinetics (PK) and safety of CSL112. Thirty-two subjects, 16 with moderate 
      RI (estimated glomerular filtration rate [eGFR] >/= 30 and < 60 mL/min/1.73 m(2) ) 
      and 16 age-, sex-, and weight-matched subjects with normal renal function (eGFR >/= 
      90 mL/min/1.73 m(2) ) were randomized 3:1 to receive a single infusion of CSL112 
      2 g (n = 6) or placebo (n = 2), or CSL112 6 g (n = 6) or placebo (n = 2). PK 
      sampling was at prespecified times from 48 hours prior to 144 hours following 
      infusions, with final safety assessments at 90 days. Renal and hepatic safety, 
      and adverse events (AEs) were monitored throughout the study. Plasma apoA-I and 
      PC PK profiles were similar between renal function cohorts at both doses. For 
      CSL112 6 g mean +/- SD apoA-I AUC(0)(-)(last) was 7670 +/- 1900 and 9170 +/- 2910 
      mg.h/dL in normal renal function and moderate RI subjects, respectively. Renal 
      apoA-I clearance was <1% of CSL112 dose. In moderate RI, sucrose clearance was 
      slower; however, approximately 70% was excreted within 48 hours in both renal 
      function cohorts. No CSL112-related serious AEs or clinically significant renal 
      or hepatic safety changes were observed. Dose adjustment of CSL112 is not 
      required in subjects with moderate RI, supporting its further investigation in 
      AMI patients with moderate RI.
CI  - (c) 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley 
      Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.
FAU - Tortorici, Michael A
AU  - Tortorici MA
AD  - CSL Behring, King of Prussia, PA, USA.
FAU - Duffy, Danielle
AU  - Duffy D
AD  - CSL Behring, King of Prussia, PA, USA.
FAU - Evans, Rebecca
AU  - Evans R
AD  - CSL Behring, King of Prussia, PA, USA.
FAU - Feaster, John
AU  - Feaster J
AD  - CSL Behring, King of Prussia, PA, USA.
FAU - Gille, Andreas
AU  - Gille A
AD  - CSL Limited, Parkville, Australia.
FAU - Mant, Timothy G K
AU  - Mant TGK
AD  - IQIVA, Reading, UK.
FAU - Wright, Samuel D
AU  - Wright SD
AD  - CSL Behring, King of Prussia, PA, USA.
FAU - D'Andrea, Denise
AU  - D'Andrea D
AD  - CSL Behring, King of Prussia, PA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02427035
GR  - DH_/Department of Health/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180921
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (APOA1 protein, human)
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (CSL112)
RN  - 0 (Lipoproteins, HDL)
RN  - 57-50-1 (Sucrose)
RN  - EC 3.1.4.- (Type C Phospholipases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apolipoprotein A-I/blood/urine
MH  - Double-Blind Method
MH  - Female
MH  - Glomerular Filtration Rate
MH  - Humans
MH  - Kidney/physiology
MH  - Lipoproteins, HDL/adverse effects/*pharmacokinetics/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Renal Insufficiency/blood/*metabolism/physiopathology/urine
MH  - Sucrose/blood/urine
MH  - Type C Phospholipases/blood
PMC - PMC6618313
OTO - NOTNLM
OT  - atherosclerosis
OT  - chronic kidney disease
OT  - lipids
OT  - pharmacokinetics
OT  - randomized controlled trial
EDAT- 2018/09/22 06:00
MHDA- 2020/07/14 06:00
PMCR- 2019/07/10
CRDT- 2018/09/22 06:00
PHST- 2018/05/29 00:00 [received]
PHST- 2018/08/16 00:00 [accepted]
PHST- 2018/09/22 06:00 [pubmed]
PHST- 2020/07/14 06:00 [medline]
PHST- 2018/09/22 06:00 [entrez]
PHST- 2019/07/10 00:00 [pmc-release]
AID - CPDD618 [pii]
AID - 10.1002/cpdd.618 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2019 Jul;8(5):628-636. doi: 10.1002/cpdd.618. Epub 2018 
      Sep 21.