Urinary Tract Infections
Conditions
Keywords
Drug-drug interaction, Cytochrome P450 3A4 (CYP3A4), 1-hydroxymidazolam, Hormonal contraceptive agent
Brief summary
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).
Interventions
DRUGGSK3882347
GSK3882347 will be administered.
DRUGMidazolam
Midazolam will be administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) not specifically listed in the exclusion or
Exclusion criteria
that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor (if required), agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight at least 50.0 kilogram (kg) (110 pound \[lbs.\]) for males and 45.0 kg (99 lbs.) for females; and body mass index (BMI) within the range 18.5 - 32.0 kg per meter square (kg/m\^2) (inclusive). * Male participants are eligible to participate if they agree to the following during the study intervention Period and for at least 3 days, after the last dose of study intervention: * Refrain from donating fresh unwashed semen Plus, either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR • Must agree to use contraception/barrier. * A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: * Is a woman of non-childbearing potential (WONCBP) . OR * Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of lesser than (\<) 1 percent (%). * A WOCBP must have a negative highly sensitive pregnancy test \[urine or serum\] as required by local regulations) within 24h before the first dose of study intervention. * The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Period 2: T1/2 of 1-hydroxy-MDZ | Up to Day 15 |
| Period 1: AUC from time zero extrapolated to infinite time (AUC [0-inf]) for plasma concentration of MDZ | Up to Day 2 |
| Period 1: AUC (0-inf) for plasma concentration of 1-hydroxy-MDZ | Up to Day 2 |
| Period 2: AUC (0-inf) for plasma concentration of MDZ | Up to Day 15 |
| Period 2: AUC (0-inf) for plasma concentration of 1-hydroxy-MDZ | Up to Day 15 |
| Period 1: Maximum plasma concentration (Cmax) of MDZ | Up to Day 2 |
| Period 1: Cmax of 1-hydroxy-MDZ | Up to Day 2 |
| Period 2: Cmax of MDZ | Up to Day 15 |
| Period 2: Cmax of 1-hydroxy-MDZ | Up to Day 15 |
| Period 1: Time to Cmax (Tmax) of MDZ | Up to Day 2 |
| Period 1: Tmax of 1-hydroxy-MDZ | Up to Day 2 |
| Period 2: Tmax of MDZ | Up to Day 15 |
| Period 2: Tmax of 1-hydroxy-MDZ | Up to Day 15 |
| Period 1: Time lag before observation of measurable concentrations (Tlag) of MDZ | Up to Day 2 |
| Period 1: Tlag of 1-hydroxy-MDZ | Up to Day 2 |
| Period 2: Tlag of MDZ | Up to Day 15 |
| Period 2: Tlag of 1-hydroxy-MDZ | Up to Day 15 |
| Period 1: Time to half-life (T1/2) of MDZ | Up to Day 2 |
| Period 1: T1/2 of 1-hydroxy-MDZ | Up to Day 2 |
| Period 2: T1/2 of MDZ | Up to Day 15 |
| Period 1: Area under the curve from time zero to 24 hours (AUC [0-24]) for plasma concentration of MDZ | Up to 24 hours |
| Period 1: AUC (0-24) for plasma concentration of 1-hydroxy-MDZ | Up to 24 hours |
| Period 2: AUC (0-24) for plasma concentration of MDZ | Up to 24 hours |
| Period 2: AUC (0-24) for plasma concentration of 1-hydroxy-MDZ | Up to 24 hours |
| Period 1: AUC from time zero to last time of quantifiable concentration (AUC [0-tau]) for plasma concentration of MDZ | Up to Day 2 |
| Period 1: AUC (0-tau) for plasma concentration of 1-hydroxy-MDZ | Up to Day 2 |
| Period 2: AUC (0-tau) for plasma concentration of MDZ | Up to Day 15 |
| Period 2: AUC (0-tau) for plasma concentration of 1-hydroxy-MDZ | Up to Day 15 |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with clinically significant changes in hematology laboratory values | Up to Day 15 |
| Number of participants with clinically significant changes in chemistry laboratory values | Up to Day 15 |
| Number of participants with clinically significant changes in urinalysis laboratory values | Up to Day 15 |
| Number of participants with clinically significant changes in vital sign values | Up to Day 15 |
| Number of participants with clinically significant changes in 12-lead electrocardiogram (ECG) readings | Up to Day 15 |
| AUC (0-24) for plasma concentration of GSK3882347 | Up to 24 hours |
| Plasma concentrations over the dosing interval tau (Ctau) of GSK3882347 | Up to Day 15 |
| Oral clearance (CL/F) of GSK3882347 | Up to Day 15 |
| Volume of distribution/ Bioavailability (Vd/F) of GSK3882347 | Up to Day 15 |
| Mean residence time (MRT) of GSK3882347 | Up to Day 15 |
| AUC(0-inf) for single dose of GSK3882347 | Up to Day 2 |
| Cmax for single dose of GSK3882347 | Up to Day 2 |
| AUC(0-tau) for repeat dose of GSK3882347 | Up to Day 15 |
| Cmax for repeat dose of GSK3882347 | Up to Day 15 |
| Accumulation ratio (Ro) using AUC (0-tau) for repeat dose of GSK3882347 | Up to Day 15 |
| Time invariance using AUC(0-tau) (repeat dose) of GSK3882347 | Up to Day 15 |
| Time invariance using AUC(0-inf) (single dose) of GSK3882347 | Up to Day 2 |
| Achievement of steady state of GSK3882347 | Up to Day 15 |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | Up to Day 15 |
Countries
United Kingdom
Outcome results
None listed