Clinical trial NCT06597500: A Study to Evaluate the Effect of Itraconazole on the Concentration of GSK3923868 in the Blood in Healthy Participants
Official title: A Single-Centre, Open-Label, Single Sequence Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of Single Inhaled Doses of GSK3923868 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: GSK3923868
Itraconazole
Pharmacokinetics
Drug interaction
Phosphatidylinositol 4-kinase beta (PI4KB)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate how itraconazole affects the blood concentration of GSK3923868 in healthy adults.


Eligibility criteria: Inclusion Criteria:

* Participants who are overtly healthy as determined by medical evaluation based on screening medical history, physical examination, vital signs, electrocardiogram (ECG) assessment, pulmonary function testing and laboratory tests.
* Body weight at least 50 kilograms (kg) and body-mass index (BMI) within the range 18.5 to 32.0 kilogram per meter squared (kg/m\^2) (inclusive).
* For female participants: A female participant is eligible to participate if the participant is a woman of non-childbearing potential (WONCBP).
* Capable of giving signed informed consent.

Exclusion Criteria:

* History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
* Alanine transaminase (ALT) and aspartate aminotransferase (AST) greater than (\>) upper limit of normal (ULN).
* Total bilirubin \> ULN (isolated bilirubin above ULN is acceptable if total bilirubin is fractionated and direct bilirubin less than (\<) 35 percentage \[%\]).
* Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* QT interval corrected for heart rate according to Frederica's formula (QTcF) \> 450 milliseconds (msec) at screening visit based on the average of triplicate ECGs.
* Past or intended use of over the counter or prescription medication, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half lives (whichever is longer) before the first dose of study treatment, unless in the opinion of the Investigator and the GSK Medical Monitor, the medication will not interfere with the study procedures or compromise participant safety.
* Recent donation of blood or blood products such that participation in this study would result in loss of blood in excess of 500 milliliters (mL) within a 56 day period.
* Exposure to more than 4 new chemical entities within 12 months before the first dosing day.
* Current enrolment or past participation in a clinical trial and has received an investigational product within the following time period before the first dosing day in this study: 30 days, 5 half lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Forced expiratory volume in 1 second (FEV1) \< 80% predicted normal value.
* Presence of hepatitis B surface antigen (HBsAg) within 3 months prior to first dose of study intervention.
* Positive hepatitis C antibody test result at screening.
* Positive hepatitis C ribonucleic acid (RNA) test result within 3 months prior to first dose of study intervention.
* Positive pre study drug/alcohol screen.
* Positive human immunodeficiency virus (HIV) antibody test.
* Current or history of drug abuse.
* History of regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of \> 14 units for males and females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Current or previous use of tobacco or nicotine containing products (e.g. cigarettes, nicotine patches or electronic devices) within 6 months before screening and/or have a smoking pack history of \> 5 pack years.
* Positive breath carbon monoxide test indicative of recent smoking at screening or each in house admission to the clinical research unit.
* Sensitivity to the study interventions (GSK3923868, itraconazole or other azole antifungal agents) or components thereof, or drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates participation in the study.

Primary outcomes:
measure: Treatment Period 1: Area under plasma concentration versus time curve (AUC) from time zero to last quantifiable concentration [AUC(0-t)] for GSK3923868 without itraconazole co-administration
timeFrame: Up to Day 3
measure: Treatment Period 2: AUC(0-t) for GSK3923868 with itraconazole co-administration
timeFrame: Up to Day 11
measure: Treatment Period 1: AUC from time zero to infinity [AUC(0-∞)] for GSK3923868 without itraconazole co-administration
timeFrame: Up to Day 3
measure: Treatment Period 2: AUC(0-∞) for GSK3923868 with itraconazole co-administration
timeFrame: Up to Day 11
measure: Treatment Period 1: Maximum observed plasma concentration (Cmax) for GSK3923868 without itraconazole co-administration
timeFrame: Up to Day 3
measure: Treatment Period 2: Cmax for GSK3923868 with itraconazole co-administration
timeFrame: Up to Day 11
measure: Treatment Period 1: Time to Cmax (Tmax) for GSK3923868 without itraconazole co-administration
timeFrame: Up to Day 3
measure: Treatment Period 2: Tmax for GSK3923868 with itraconazole co-administration
timeFrame: Up to Day 11
Secondary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Up to Day 30
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Up to Day 30
measure: Number of participants with clinically significant changes in laboratory values
timeFrame: Up to Day 30
measure: Number of participants with clinically significant changes in vital signs
timeFrame: Up to Day 30
measure: Number of participants with clinically significant changes in 12-lead electrocardiogram (ECG) measurements
timeFrame: Up to Day 30
measure: Treatment Period 2: AUC(0-t) for itraconazole and hydroxy-itraconazole
timeFrame: On Days 1 and 5
measure: Treatment Period 2: AUC(0-∞) for itraconazole and hydroxy-itraconazole
timeFrame: On Days 1 and 5
measure: Treatment Period 2: Cmax for itraconazole and hydroxy-itraconazole
timeFrame: On Days 1 and 5
measure: Treatment Period 2: Tmax for itraconazole and hydroxy-itraconazole
timeFrame: On Days 1 and 5
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: