The objective of this study is to determine the magnitude and clinical relevance of a potential drug-drug interaction of GSK3882347 with midazolam (MDZ) in healthy participants. This study assesses the effect of GSK3882347 as an inducer of Cytochrome P450 3A4 (CYP3A4) using MDZ, a sensitive substrate of hepatic and intestinal CYP3A4. The study will investigate MDZ pharmacokinetic (PK) effect in two dosing periods: Period 1: A single dose of MDZ Period 2: 14-days of once daily repeat dosing of GSK3882347 followed by single dose of MDZ co-administered with GSK3882347 on Day 15 (14-days has been selected as this duration is required in order to maximize any potential CYP3A4 enzyme induction).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Midazolam will be administered.
GSK3882347 will be administered.
GSK Investigational Site
Cambridge, United Kingdom
Period 1: Area under the curve from time zero to 24 hours (AUC [0-24]) for plasma concentration of MDZ
Time frame: Up to 24 hours
Period 1: AUC (0-24) for plasma concentration of 1-hydroxy-MDZ
Time frame: Up to 24 hours
Period 2: AUC (0-24) for plasma concentration of MDZ
Time frame: Up to 24 hours
Period 2: AUC (0-24) for plasma concentration of 1-hydroxy-MDZ
Time frame: Up to 24 hours
Period 1: AUC from time zero to last time of quantifiable concentration (AUC [0-tau]) for plasma concentration of MDZ
Time frame: Up to Day 2
Period 1: AUC (0-tau) for plasma concentration of 1-hydroxy-MDZ
Time frame: Up to Day 2
Period 2: AUC (0-tau) for plasma concentration of MDZ
Time frame: Up to Day 15
Period 2: AUC (0-tau) for plasma concentration of 1-hydroxy-MDZ
Time frame: Up to Day 15
Period 1: AUC from time zero extrapolated to infinite time (AUC [0-inf]) for plasma concentration of MDZ
Time frame: Up to Day 2
Period 1: AUC (0-inf) for plasma concentration of 1-hydroxy-MDZ
Time frame: Up to Day 2
Period 2: AUC (0-inf) for plasma concentration of MDZ
Time frame: Up to Day 15
Period 2: AUC (0-inf) for plasma concentration of 1-hydroxy-MDZ
Time frame: Up to Day 15
Period 1: Maximum plasma concentration (Cmax) of MDZ
Time frame: Up to Day 2
Period 1: Cmax of 1-hydroxy-MDZ
Time frame: Up to Day 2
Period 2: Cmax of MDZ
Time frame: Up to Day 15
Period 2: Cmax of 1-hydroxy-MDZ
Time frame: Up to Day 15
Period 1: Time to Cmax (Tmax) of MDZ
Time frame: Up to Day 2
Period 1: Tmax of 1-hydroxy-MDZ
Time frame: Up to Day 2
Period 2: Tmax of MDZ
Time frame: Up to Day 15
Period 2: Tmax of 1-hydroxy-MDZ
Time frame: Up to Day 15
Period 1: Time lag before observation of measurable concentrations (Tlag) of MDZ
Time frame: Up to Day 2
Period 1: Tlag of 1-hydroxy-MDZ
Time frame: Up to Day 2
Period 2: Tlag of MDZ
Time frame: Up to Day 15
Period 2: Tlag of 1-hydroxy-MDZ
Time frame: Up to Day 15
Period 1: Time to half-life (T1/2) of MDZ
Time frame: Up to Day 2
Period 1: T1/2 of 1-hydroxy-MDZ
Time frame: Up to Day 2
Period 2: T1/2 of MDZ
Time frame: Up to Day 15
Period 2: T1/2 of 1-hydroxy-MDZ
Time frame: Up to Day 15
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time frame: Up to Day 15
Number of participants with clinically significant changes in hematology laboratory values
Time frame: Up to Day 15
Number of participants with clinically significant changes in chemistry laboratory values
Time frame: Up to Day 15
Number of participants with clinically significant changes in urinalysis laboratory values
Time frame: Up to Day 15
Number of participants with clinically significant changes in vital sign values
Time frame: Up to Day 15
Number of participants with clinically significant changes in 12-lead electrocardiogram (ECG) readings
Time frame: Up to Day 15
AUC (0-24) for plasma concentration of GSK3882347
Time frame: Up to 24 hours
Plasma concentrations over the dosing interval tau (Ctau) of GSK3882347
Time frame: Up to Day 15
Oral clearance (CL/F) of GSK3882347
Time frame: Up to Day 15
Volume of distribution/ Bioavailability (Vd/F) of GSK3882347
Time frame: Up to Day 15
Mean residence time (MRT) of GSK3882347
Time frame: Up to Day 15
AUC(0-inf) for single dose of GSK3882347
Time frame: Up to Day 2
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Cmax for single dose of GSK3882347
Time frame: Up to Day 2
AUC(0-tau) for repeat dose of GSK3882347
Time frame: Up to Day 15
Cmax for repeat dose of GSK3882347
Time frame: Up to Day 15
Accumulation ratio (Ro) using AUC (0-tau) for repeat dose of GSK3882347
Time frame: Up to Day 15
Time invariance using AUC(0-tau) (repeat dose) of GSK3882347
Time frame: Up to Day 15
Time invariance using AUC(0-inf) (single dose) of GSK3882347
Time frame: Up to Day 2
Achievement of steady state of GSK3882347
Time frame: Up to Day 15