The safety and single-dose pharmacokinetics of CD101IV: results from a phase 1, dose-escalation study

Dirk Thye

Abstract: 

Background: CD101 IV is a novel echinocandin being developed as a once-weekly administered
antifungal for candidemia and invasive candidiasis. CD101 has demonstrated potent in vitro and in
vivo activity against a broad range of Candida and Aspergillus species. CD101 IV was evaluated in a
randomized, double-blind, placebo-controlled, dose-escalation study designed to establish the safety,
tolerability, and pharmacokinetics of single intravenous (IV) doses of CD101 IV.
Material/methods: In four sequential cohorts of eight subjects (n=6, active; n=2, placebo), CD101
was administered IV as a single dose infused over 1 h (50 mg, 100 mg, 200 mg, 400 mg), with dose
escalation determined by pre-defined safety criteria. Extensive plasma and urine sampling over
21 days was performed to assess the pharmacokinetics of CD101 IV. Safety and tolerability was
assessed by adverse events (AEs), vital signs, physical exams, electrocardiograms (ECGs),
haematology and clinical chemistry laboratories up to 21 days after dosing.
Results: A total of 32 subjects were randomized to the study, with 31 subjects completing all study
assessments. One subject prematurely withdrew for personal reasons unrelated to safety or
tolerability. Subjects were primarily Hispanic (94%), and males and females were approximately
equally represented (53% and 47%, respectively). There were no Serious Adverse Events (SAEs),
severe AEs, or dose-response relationships for overall AEs. The majority of AEs were mild, and all
AEs completely resolved by the end of the study. There were no drug-related AEs resulting from
clinically significant haematology or clinical chemistry laboratory abnormalities at any dose. In
addition, there were no safety issues related to ECGs, vital signs, or physical exam findings. Across
the 50 to 400 mg dose range, CD101 plasma exposures were generally dose-proportional, with
average Cmax ranging from 2.76 to 22.7 μg/mL and corresponding AUC0-168h ranging from
145 to 1160 μgh/mL. Apparent clearance of CD101 was remarkably low (<0.3 L/hour), and
its half-life was long (t1/2 >80 h). Excretion of CD101 in urine was minimal (<1%).
Conclusions: CD101 IV was safe and well tolerated as a single dose up to 400 mg, exhibited long
plasma t1/2, and maintained plasma exposures that support a once-weekly dosing regimen. The overall
safety, tolerability and PK profile of CD101 support continued development as a once-weekly therapy
for invasive fungal infections.

2016

abstract No: 

#2095

Full conference title: 

26th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 26th (2016)