PMID- 36285509
OWN - NLM
STAT- MEDLINE
DCOM- 20230205
LR  - 20230227
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 12
IP  - 2
DP  - 2023 Feb
TI  - Effect of Severe Renal Impairment on Pharmacokinetics, Safety, and Tolerability 
      of ACT-1014-6470, a Novel Oral Complement Factor 5a Receptor 1 Antagonist.
PG  - 152-158
LID - 10.1002/cpdd.1184 [doi]
AB  - The aim of this study was to examine the safety and the effect of severe renal 
      impairment (RI) on the pharmacokinetics of ACT-1014-6470, a novel oral complement 
      factor 5a receptor 1 antagonist. A phase 1 single-center, open-label, 
      single-dose, parallel-group study was conducted in subjects with severe RI 
      (n = 8) compared to demographically pairwise matched subjects with normal renal 
      function (n = 8). Plasma levels of ACT-1014-6470 were measured up to 120 hours 
      following an oral 40-mg dose. Safety evaluations included adverse events (AEs), 
      vital signs, hematology, coagulation, clinical chemistry tests, and 
      electrocardiograms. All 16 subjects completed the study. Relative to subjects 
      with normal renal function, ACT-1014-6470 time to maximum plasma concentration 
      was delayed with a median of differences of 3 hours. The maximum plasma 
      concentration and the area under the plasma concentration-time profile from time 
      zero to infinity were comparable indicated by geometric mean ratios (90%CI) of 
      0.85 (0.53-1.37) and 1.17 (0.73-1.85), respectively. Four transient and mild AEs 
      in three subjects with severe RI were reported; three AEs were considered not 
      related to ACT-1014-6470. These results support the use of ACT-1014-6470 in 
      subjects with mild to severe RI without the need of dose adjustment.
CI  - (c) 2022, The American College of Clinical Pharmacology.
FAU - Hammann-Hanni, Anya
AU  - Hammann-Hanni A
AD  - Department of Clinical Pharmacology, Idorsia Pharmaceuticals Ltd, Allschwil, 
      Switzerland.
FAU - Kaufmann, Priska
AU  - Kaufmann P
AD  - Department of Clinical Pharmacology, Idorsia Pharmaceuticals Ltd, Allschwil, 
      Switzerland.
FAU - Klein, Gernot
AU  - Klein G
AD  - APEX GmbH, Munich, Germany.
FAU - Schmid, Karin
AU  - Schmid K
AD  - APEX GmbH, Munich, Germany.
FAU - Dingemanse, Jasper
AU  - Dingemanse J
AD  - Department of Clinical Pharmacology, Idorsia Pharmaceuticals Ltd, Allschwil, 
      Switzerland.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221026
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 65522-14-7 (Factor Va)
SB  - IM
MH  - Humans
MH  - Area Under Curve
MH  - *Factor Va
MH  - *Renal Insufficiency
OTO - NOTNLM
OT  - C5aR1 antagonist
OT  - complement system
OT  - pharmacokinetics
OT  - phase 1
OT  - renal impairment
EDAT- 2022/10/27 06:00
MHDA- 2023/02/03 06:00
CRDT- 2022/10/26 04:02
PHST- 2022/06/28 00:00 [received]
PHST- 2022/09/20 00:00 [accepted]
PHST- 2022/10/27 06:00 [pubmed]
PHST- 2023/02/03 06:00 [medline]
PHST- 2022/10/26 04:02 [entrez]
AID - 10.1002/cpdd.1184 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2023 Feb;12(2):152-158. doi: 10.1002/cpdd.1184. Epub 
      2022 Oct 26.