PMID- 35439347
OWN - NLM
STAT- MEDLINE
DCOM- 20220718
LR  - 20221014
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 15
IP  - 7
DP  - 2022 Jul
TI  - A phase I randomized, double-blind, single subcutaneous dose escalation study to 
      determine the safety, tolerability, and pharmacokinetics of rezafungin in healthy 
      adult subjects.
PG  - 1592-1598
LID - 10.1111/cts.13286 [doi]
AB  - Rezafungin is a novel echinocandin being developed for the treatment and 
      prevention of invasive fungal infections. The objectives of this randomized, 
      double-blind study in healthy adults were to determine the safety, tolerability, 
      and pharmacokinetics of rezafungin after subcutaneous (s.c.) administration. The 
      study design consisted of six sequential cohorts of eight subjects, except for 
      the first cohort with four subjects. The subjects were randomized in a 3:1 ratio 
      of rezafungin to placebo and were to receive a single dose of 1, 10, 30, 60, 100, 
      or 200 mg. The most common adverse events (AEs) were increased alanine 
      aminotransferase and sinus bradycardia (unsolicited) and erythema at the 
      injection site (solicited). Unsolicited AEs were generally mild to moderate and 
      not rezafungin-related. Although the study was terminated after the 10 mg dose 
      cohort due to concerns of potential increased severity of injection site 
      reactions, no predetermined dose escalation halting criteria were met. Following 
      the 10 mg single s.c. dose of rezafungin (n = 6), the geometric mean (GM) maximum 
      concentration (C(max) ) was 105.0 ng/ml and the median time to C(max) was 144 h. 
      The GM area under the concentration-time curve was 32,770 ng*h/ml. The median 
      estimated terminal half-life was 193 h. The GM apparent oral clearance was 
      0.255 L/h and the GM apparent volume of distribution was 68.5 L. This study 
      demonstrates that a single s.c. dose of rezafungin in healthy adult subjects: (1) 
      did not result in serious AEs, death, or withdrawal from the study due to an AE; 
      and (2) produced a pharmacokinetic profile with long exposure period 
      postadministration. In an effort to reduce the occurrence of injection site 
      reactions, a re-evaluation of the rezafungin s.c. formulation could be considered 
      in the future.
CI  - (c) 2022 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Gu, Kenan
AU  - Gu K
AD  - National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
FAU - Ruff, Dennis
AU  - Ruff D
AD  - ICON Early Phase Services Clinical Research Unit, San Antonio, Texas, USA.
FAU - Key, Cassandra
AU  - Key C
AD  - ICON Early Phase Services Clinical Research Unit, San Antonio, Texas, USA.
FAU - Thompson, Marissa
AU  - Thompson M
AD  - Emmes Company, LLC, Rockville, Maryland, USA.
FAU - Jiang, Shoshanna
AU  - Jiang S
AD  - Emmes Company, LLC, Rockville, Maryland, USA.
FAU - Sandison, Taylor
AU  - Sandison T
AD  - Cidara Therapeutics, San Diego, California, USA.
FAU - Flanagan, Shawn
AU  - Flanagan S
AD  - Cidara Therapeutics, San Diego, California, USA.
LA  - eng
GR  - HHSN272201500007C/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20220504
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (Echinocandins)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - *Echinocandins
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - *Injection Site Reaction
PMC - PMC9283735
COIS- Shawn Flanagan and Taylor Sandison are employees and stockholders of Cidara 
      Therapeutics, Inc. All other authors declared no competing interests for this 
      work.
EDAT- 2022/04/20 06:00
MHDA- 2022/07/19 06:00
PMCR- 2022/07/01
CRDT- 2022/04/19 17:12
PHST- 2022/03/18 00:00 [revised]
PHST- 2021/11/08 00:00 [received]
PHST- 2022/04/04 00:00 [accepted]
PHST- 2022/04/20 06:00 [pubmed]
PHST- 2022/07/19 06:00 [medline]
PHST- 2022/04/19 17:12 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - CTS13286 [pii]
AID - 10.1111/cts.13286 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2022 Jul;15(7):1592-1598. doi: 10.1111/cts.13286. Epub 2022 May 
      4.