This is an open-label study to evaluate the PK of FF/UMEC/VI in dose combinations of 100/62.5/25 mcg after single and repeat dose administration from a DPI in healthy Chinese subjects. This study will evaluate the systemic pharmacokinetics (PK), of FF/UMEC/VI in Chinese healthy population when administered using dry powder inhaler (DPI)as a blended combination of UMEC/VI in one strip and FF in the second strip in dose combinations of 100/62.5/25 mcg. The triple, fixed dose combination product Fluticasone furoate(FF)/ Vilanterol (VI) /Umeclidinium bromide (UMEC) with new configuration enables the delivery of inhaled long-acting muscarinic antagonist (LAMA), Long-acting beta2 agonist (LABA) and inhaled corticosteroid (ICS) from a single device. Approximately 16 subjects will be enrolled in the study. After taking into account the allowable time windows for screening, treatment and follow-up, a subject will be in the study for a maximum duration of 6-7 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
FF is a dry white powder blended with lactose. It is the first strip of DPI. Per blister contains 100 mcg of dose
VI and UMEC bromide combination is a dry white powder blended with lactose and magnesium stearate. It is the second strip of DPI. Per blister contains 25 mcg/62.5 mcg of VI/UMEC dose
GSK Investigational Site
Shanghai, China
Maximum observed concentration (Cmax) of FF, UMEC and VI after single inhaled dose on Day1
Time frame: Pre-dose, 5 minutes (min), 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1
Time of occurrence of Cmax (tmax) of FF, UMEC and VI after single inhaled dose on Day1
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1
Area under the concentration time curve (AUC) between zero and the time to the last measurable concentration (AUC (0-t)) of FF, UMEC and VI after single inhaled dose on Day1
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1
AUC from time zero (pre-dose) to the time of last common measurable time-point within subject /treatment/study (AUC (0-t')) of FF, UMEC and VI after single inhaled dose on Day1
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1
Elimination rate constant (kel) of FF, UMEC and VI after single inhaled dose on Day1
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1
Terminal half-life (t1/2) of FF, UMEC and VI after single inhaled dose on Day1
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1
AUC between zero and the infinity (AUC (0-inf)) of FF, UMEC and VI after single inhaled dose on Day1
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h and 8 h post dose on Day 1
tmax after repeat inhaled dose of FF, UMEC and VI on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
AUC (0-t) of FF, UMEC and VI after repeat inhaled dose on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
AUC (0-t') of FF, UMEC and VI after repeat inhaled dose on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
Maximum concentration observed at steady state (Css_max) of FF, UMEC and VI after repeat inhaled dose on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
Minimum concentration observed at steady state (Css_min) of FF, UMEC and VI after repeat inhaled dose on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
Average steady state concentration (Css_av) of FF, UMEC and VI after repeat inhaled dose on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
AUC at steady state (AUCss) of FF, UMEC and VI after repeat inhaled dose on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
Observed accumulation ratio (Ro) of FF, UMEC and VI after repeat inhaled dose on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
Maximum observed concentration ratio (RCmax) of FF, UMEC and VI after repeat inhaled dose on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
Degree of fluctuation (DF) of FF, UMEC and VI after repeat inhaled dose on Day 7
Time frame: Pre-dose, 5 min, 8 min, 10 min, 12 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h post dose on Day 7
Number of subjects with any Adverse Events (AEs) and any serious adverse events (SAEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement and associated with liver injury and impaired liver function will be categorized as SAE.
Time frame: Up to Day 17
Pulse rate as a measure of safety
Pulse rate will be taken in sitting position having rested in this position for at least 5 minutes
Time frame: Up to Day 17
Systolic and diastolic blood pressure as a measure of safety
Systolic and diastolic blood pressure will be taken in sitting position having rested in this position for at least 5 minutes
Time frame: Up to Day 17
Electrocardiogram (ECG) as a measure of safety
12-Lead ECG will be taken in a supine position, having rested in this position for at least 5 minutes.
Time frame: Up to Day 17
Number of subjects with abnormal hematology values
Hematological parameters includes: platelet count, red blood cell (RBC) count, absolute white blood cell (WBC) count, hemoglobin, hematocrit, RBC indices (includes: mean corpuscular volume \[MCV\], mean corpuscular hemoglobin \[MCH\], MCH concentration \[MCHC\]) and WBC differential count (includes: neutrophils, lymphocytes, monocytes, eosinophils and basophils)
Time frame: Up to Day 17
Number of subjects with abnormal clinical biochemistry values
Clinical chemistry includes: blood Urea Nitrogen (BUN), creatinine, Glucose (fasting), potassium, chloride, calcium, sodium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), alkaline phosphatase (ALP), total and direct bilirubin, uric acid, albumin and total protein
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to Day 17
Number of subjects with abnormal urinalysis results
Urinalysis includes: Specific gravity, analysis of pH, glucose, protein, blood \& ketones by dipstick method, and microscopic examination (if blood or protein is abnormal)
Time frame: Up to Day 17