2022
DOI: 10.1002/cpdd.1070
|View full text |Cite
|
Sign up to set email alerts
|

Pharmacokinetics and Macrophage Inhibitory Cytokine‐1 Pharmacodynamics of the Murine Double Minute 2 Inhibitor, Navtemadlin (KRT‐232) in Fed and Fasted Healthy Subjects

Abstract: This single 60‐mg dose, 4‐period crossover study assessed the effect of food and formulation change on navtemadlin (KRT‐232) pharmacokinetics (PK) and macrophage inhibitory cytokine‐1 (MIC‐1) pharmacodynamics. Healthy subjects (N = 30) were randomized to 3 treatment sequences, A: new tablet, fasted (reference, dosed twice); B: new tablet, 30 minutes after a high‐fat meal (test 1); C: old tablet, fasted (test 2). PK/pharmacodynamic parameters were measured over 0 to 96 hours. Adverse events were mild without an… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1

Citation Types

0
1
0

Year Published

2022
2022
2024
2024

Publication Types

Select...
2
1

Relationship

0
3

Authors

Journals

citations
Cited by 3 publications
(1 citation statement)
references
References 21 publications
0
1
0
Order By: Relevance
“…Although pharmacodynamic markers in the tumor could possibly be detected at earlier time points, circulating tumor proteins probably require additional time for detection. In concert with this, in normal healthy adults given a dose of the MDM2 inhibitor navtemadlin, peak GDF-15 levels were observed after a lag time of 8–12 hours after administration ( 46 ). Further studies focused on understanding the kinetics of GDF-15 after administration of MDM2 inhibitors are essential for determining if GDF-15 could be an important clinical indicator for tracking an active p53 response in MCC.…”
Section: Discussionmentioning
confidence: 91%
“…Although pharmacodynamic markers in the tumor could possibly be detected at earlier time points, circulating tumor proteins probably require additional time for detection. In concert with this, in normal healthy adults given a dose of the MDM2 inhibitor navtemadlin, peak GDF-15 levels were observed after a lag time of 8–12 hours after administration ( 46 ). Further studies focused on understanding the kinetics of GDF-15 after administration of MDM2 inhibitors are essential for determining if GDF-15 could be an important clinical indicator for tracking an active p53 response in MCC.…”
Section: Discussionmentioning
confidence: 91%