The current study will help to increase our understanding of the pharmacokinetics (PK) of danirixin. The primary objective of the study is to estimate the relative bioavailability of danirixin Hydrobromide (HBr) tablet, when compared to danirixin free base (FB). Safety and tolerability information for oral administration of danrixin HBr tablets in elderly subjects will also be obtained. Secondarily, this study will evaluate effect of food on PK of danirixin HBr, effect of gastric acid suppression, and within-subject PK variability of danirixin HBr. The outcome of this study will contribute to the selection of the most appropriate formulation/dosing regimen for future studies. This is an open-label, 5-period crossover study. Study will be conducted in 18 healthy elderly subjects. Screening will occur within 42 days prior to Day 1 of period 1. The Treatment Periods will be separated by a washout period of a minimum 5 days. Follow-up will be done within 3 to 10 days post last dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Danirixin HBr 50 mg IR Tablet is white, film-coated, oval-shaped tablet for oral administration.
Danirixin FB 50 mg IR Tablet is white, film-coated, capsule-shaped tablet for oral administration.
Prilosec (omeprazole) 40 mg delayed-release capsule is opaque, hard gelatin, apricot, and amethyst colored capsules, coded 743 on cap and PRILOSEC 40 on the body for oral administration.
GSK Investigational Site
Overland Park, Kansas, United States
Composite of Danirixin PK parameters
Danirixin PK parameters area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-inf\]) and maximum observed concentration (Cmax) following single dose administration of FB tablet (reference), relative to HBr tablet (test) will be assessed.
Time frame: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours (hrs) post-dose in each period
Number of participants with adverse events (AE) /serious adverse event (SAE) as a measure of safety and tolerability
AE/SAE will be collected from the start of study treatment and until the follow-up visit or contact for study treatment period 5. Intensity of AEs will be categorized as mild, moderate or severe. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity is a congenital anomaly/birth defect is associated with liver injury and impaired liver function.
Time frame: Up to Day 36
Composite of vital signs as a measure of safety and tolerability
Vital signs will include temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate.
Time frame: Up to Day 31
Electrocardiogram (ECG) as a measure of safety and tolerability
ECG will be obtained at selected time-points during the study.
Time frame: Up to Day 29
Composite of clinical laboratory tests as a measure of safety and tolerability
Clinical laboratory tests will include hematology, clinical chemistry and urinalysis.
Time frame: Up to Day 31
Composite of other Danirixin PK parameters
Other Danirixin PK parameters area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC\[0-t\]), time of occurrence of Cmax (tmax), terminal phase half-life (t1/2), time of last quantifiable concentration (tlast) and lag time before observation of drug concentrations in sampled matrix (tlag) following single dose administration of FB tablet (reference), relative to HBr tablet (test) will be assessed.
Time frame: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hrs post-dose in each period
Composite of Danirixin PK parameters to estimate the food effect
Danirixin PK parameters AUC(0-inf), AUC(0-t), Cmax, tmax, t1/2, tlast and tlag following danirixin HBr tablet formulation under fasting and fed state will be assessed.
Time frame: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hrs post-dose in each period
Composite of Danirixin PK parameters to estimate the effect of Omepazole (OMP)
Danirixin PK parameters AUC(0-inf), AUC(0-t), Cmax, tmax, t1/2, tlast and tlag following danirixin HBr tablet formulation with or without concomitant, steady state OMP will be assessed.
Time frame: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hrs post-dose in each period
Composite of Danirixin PK parameters to estimate the within-subject variability of danirixin
Danirixin PK parameters AUC(0-inf), AUC(0-t), Cmax following danirixin HBr tablet formulation under fed conditions will be assessed.
Time frame: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hrs post-dose in each period
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