Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2269557 to Japanese Healthy Subjects
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Interventions
- Drug: Placebo ELLIPTA DPIDrug: GSK2269557 ELLIPTA DPI
- Registration Number
- NCT02972905
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
GSK2269557 is a potent and highly selective inhaled Phosphoinositide 3-Kinase (PI3K) delta inhibitor being developed as an anti-inflammatory and anti-infective agent for the treatment of inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD). The purpose of the study is to assess the safety, tolerability and pharmacokinetics (PK) of single and repeat doses of GSK2269557 administered via the ELLIPTA dry powder inhaler (DPI) to healthy Japanese subjects. This is the first time for Japanese subjects that GSK2269557 will be administered via the ELLIPTA DPI with the addition of magnesium stearate.
In each group of this study, subjects will receive a single dose of either GSK2269557 or placebo in Session 1 and receive daily dose of GSK2269557 or placebo for 10 days in Session 2. Session 1 of the next dose strength may be run in parallel with the Session 2 of the previous dose. The doses planned for the study are 200 micrograms (mcg), 500 mcg and 700 mcg. There will be at least 10 days washout between the two dosing sessions. Follow up period will start 10 days (+-1 day) after the last dose of Session 2. A total number of 36 subjects will be enrolled for the study with 27 subjects receiving a dose strength of GSK2269557 and 9 subjects will receive each dose strength of GSK2269557. ELLIPTA is a trademark of the GSK group of companies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Session 1: Placebo Placebo ELLIPTA DPI Subjects will receive a single dose inhalation of GSK2269557 matching placebo via the ELLIPTA DPI. The washout period between the two dosing sessions will be at least 10 days. Session 1: GSK2269557 200 mcg GSK2269557 ELLIPTA DPI Subjects will receive a single dose inhalation of GSK2269557 200 mcg via the ELLIPTA DPI. The washout period between the two dosing sessions will be at least 10 days. Session 1: GSK2269557 500 mcg GSK2269557 ELLIPTA DPI Subjects will receive a single dose inhalation of GSK2269557 500 mcg via the ELLIPTA DPI. The washout period between the two dosing sessions will be at least 10 days. Session 1: GSK2269557 700 mcg GSK2269557 ELLIPTA DPI Subjects will receive a single dose inhalation of GSK2269557 700 mcg via the ELLIPTA DPI. The washout period between the two dosing sessions will be at least 10 days. Session 2: Placebo Placebo ELLIPTA DPI Subjects will receive repeated doses of GSK2269557 matching Placebo once daily via the ELLIPTA DPI for 10 days. The washout period between the two dosing sessions will be at least 10 days. Session 2: GSK2269557 200 mcg GSK2269557 ELLIPTA DPI Subjects will receive repeated doses of GSK2269577 200mcg once daily via the ELLIPTA DPI for 10 days. The washout period between the two dosing sessions will be at least 10 days. Session 2: GSK2269557 500 mcg GSK2269557 ELLIPTA DPI Subjects will receive repeated doses of GSK2269577 500mcg once daily via the ELLIPTA DPI for 10 days. The washout period between the two dosing sessions will be at least 10 days. Session 2: GSK2269557 700 mcg GSK2269557 ELLIPTA DPI Subjects will receive repeated doses of GSK2269577 700mcg once daily via the ELLIPTA DPI for 10 days. The washout period between the two dosing sessions will be at least 10 days.
- Primary Outcome Measures
Name Time Method Session 1: Number of subjects having abnormal urinalysis as a measure of safety Approximately up to 4 days Urine samples will be collected to analyse specific gravity, pH, glucose, protein, blood, ketones, bilirubin, and urobilinogen for dipstick, and microscopic examination
Session 2: Number of subjects having abnormal urinalysis as a measure of safety Approximately up to 22 days Urine samples will be collected to analyse specific gravity, pH, glucose, protein, blood, ketones, bilirubin, and urobilinogen for dipstick, and microscopic examination
Session 1: Body temperature assessment as a safety measure Approximately up to 4 days Temperature will be recorded in a supine position after 5 minutes rest
Session 2: Body temperature assessment as a safety measure Approximately up to 22 days Temperature will be recorded in a supine position after 5 minutes rest
Session 1: Blood pressure assessment as a safety measure Approximately up to 4 days Systolic and diastolic blood pressure will be measured in a supine positon after 5 minutes rest
Session 2: Measurement of pulse rate as a safety measure Approximately up to 22 days Pulse rate will be measured in a supine position after 5 minutes rest
Session 1: Electrocardiogram (ECG) assessment as a measure of safety. Approximately up to 4 days Single 12-lead ECG will be obtained in a supine position after 5 minutes rest using an ECG machine that measures PR, QRS, QT, and Corrected QT interval by Fridericia's formula (QTcF) intervals. Single ECGs will be obtained at each time point.
Session 2: ECG assessment as a measure of safety. Approximately up to 22 days Single 12-lead ECG will be obtained in a supine position after 5 minutes rest using an ECG machine that measures PR, QRS, QT, and QTcF intervals. Single ECGs will be obtained at each time point.
Session 1: Number of subjects having abnormal clinical laboratory parameters as a measure of safety Approximately up to 4 days Blood samples will be collected to analyse blood urea nitrogen, creatinine, glucose (fasting), uric acid, high density lipoprotein-cholesterol, amylase, potassium, sodium, calcium, triglycerides, lactate dehydrogenase (LDH), chloride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol, gamma-glutamyl transpeptidase (GGT), phosphorus, total bilirubin, direct bilirubin, total protein, albumin, low density lipoprotein-cholesterol, creatine phosphokinase (CPK)
Session 1: Trough observed plasma drug concentration (Ctrough) of GSK2269557 following a single dose administration Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating Ctrough
Session 1: Maximum observed plasma concentration (Cmax) of GSK2269557 following a single dose administration Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax
Session 1: Maximum/trough observed plasma drug concentration (Cmax/Ctrough) of GSK2269557 following a single dose administration Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax/Ctrough
Session 2: Trough observed plasma drug concentration (Ctrough) of GSK2269557 following repeat dose administration Day 1: pre-dose, 5 min and 24 h post-dose; Day 2: 5 min post-dose; Days 3, 4, 5, 6, 7, 8, and 9: pre-dose and 5 min post-dose; Day 10: pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, 6 h post-dose; 24 h, 48 h, 72 h, 96 h and 120 h post-Day 10 dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating Ctrough
Number of subjects with any adverse event(s) (AE) and serious adverse event(s) (SAE) Approximately up to 37 days An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Session 2: Number of subjects having abnormal clinical laboratory parameters as a measure of safety Approximately up to 22 days Blood samples will be collected to analyse blood urea nitrogen, creatinine, glucose (fasting), uric acid, high density lipoprotein-cholesterol, amylase, potassium, sodium, calcium, triglycerides, LDH, chloride, AST, ALT, ALP, total cholesterol, GGT, phosphorus, total bilirubin, direct bilirubin, total protein, albumin, low density lipoprotein-cholesterol, CPK
Session 1:Number of subjects having abnormal hematology laboratory parameters as a measure of safety Approximately up to 4 days Blood samples will be collected to analyse platelet count, Red Blood Cells (RBC) count, hemoglobin, hematocrit, RBC Indices, mean corpuscular volume ( MCV), mean corpuscular hemoglobin (MCH), percent reticulocytes, White Blood Cells (WBC), neutrophils, lymphocytes, monocytes, eosionophils, and basophils
Session 2: Number of subjects having abnormal hematology laboratory parameters as a measure of safety Approximately up to 22 days Blood samples will be collected to analyse platelet count, RBC count, hemoglobin, hematocrit, RBC Indices, MCV, MCH, percent reticulocytes, WBC, neutrophils, lymphocytes, monocytes, eosionophils, and basophils
Session 1: Spirometry assessment as a safety measure Approximately up to 4 days Spirometry assessments will be performed whilst the subject is in a standing position. Assessments will be repeated until 3 technically acceptable measurements have been made.
Session 2: Spirometry assessment as a safety measure Approximately up to 22 days Spirometry assessments will be performed whilst the subject is in a standing position. Assessments will be repeated until 3 technically acceptable measurements have been made.
Session 1: Area under the plasma concentration curve (AUC) from time zero to the time of last quantifiable concentration [AUC(0-t)] Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72hours (h) post-dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC \[0-t\]
Session 1: AUC from time zero to 24 hours post dose [AUC(0-24)] of GSK2269557 following a single dose administration Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC\[0-24\]
Session 1: AUC from time zero to infinity [AUC(0-infinity)] of GSK2269557 following a single dose administration Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC (0-infinity).
Session 2: AUC from time zero to the time of last quantifiable concentration [AUC(0-t)] of GSK2269557 following repeat dose administration Day 1: pre-dose, 5 min and 24 h post-dose; Day 2: 5 min post-dose; Days 3, 4, 5, 6, 7, 8, and 9: pre-dose and 5 min post-dose; Day 10: pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, 6 h post-dose; 24 h, 48 h, 72 h, 96 h and 120 h post-Day 10 dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC \[0-t\]
Session 2: AUC from time zero to 24 hours post dose [AUC(0-24)] of GSK2269557 following repeat dose administration Day 1: pre-dose, 5 min and 24 h post-dose; Day 2: 5 min post-dose; Days 3, 4, 5, 6, 7, 8, and 9: pre-dose and 5 min post-dose; Day 10: pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, 6 h post-dose; 24 h, 48 h, 72 h, 96 h and 120 h post-Day 10 dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC\[0-24\]
Session 2: AUC from time zero to infinity [AUC(0-infinity)] of GSK2269557 following repeat dose administration Day 1: pre-dose, 5 min and 24 h post-dose; Day 2: 5 min post-dose; Days 3, 4, 5, 6, 7, 8, and 9: pre-dose and 5 min post-dose; Day 10: pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, 6 h post-dose; 24 h, 48 h, 72 h, 96 h and 120 h post-Day 10 dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC (0-infinity)
Session 2: Blood pressure assessment as a safety measure Approximately up to 22 days Systolic and diastolic blood pressure will be measured in a supine position after 5 minutes rest
Session 1: Measurement of pulse rate as a safety measure Approximately up to 4 days Pulse rate will be measured in a supine position after 5 minutes rest
Session 2: Maximum observed plasma concentration (Cmax) of GSK2269557 following repeat dose administration Day 1: pre-dose, 5 min and 24 h post-dose; Day 2: 5 min post-dose; Days 3, 4, 5, 6, 7, 8, and 9: pre-dose and 5 min post-dose; Day 10: pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, 6 h post-dose; 24 h, 48 h, 72 h, 96 h and 120 h post-Day 10 dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax
Session 2: Maximum/trough observed plasma drug concentration (Cmax/Ctrough) of GSK2269557 following repeat dose administration Day 1: pre-dose, 5 min and 24 h post-dose; Day 2: 5 min post-dose; Days 3, 4, 5, 6, 7, 8, and 9: pre-dose and 5 min post-dose; Day 10: pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, 6 h post-dose; 24 h, 48 h, 72 h, 96 h and 120 h post-Day 10 dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax/Ctrough
Session 1: Time to maximum observed plasma drug concentration (Tmax) of GSK2269557 following a single dose administration Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating tmax
Session 1: Terminal half-life (t1/2) of GSK2269557 following a single dose administration Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating t1/2
Session 2: Terminal half-life (t1/2) of GSK2269557 following repeat dose administration Day 1: pre-dose, 5 min and 24 h post-dose; Day 2: 5 min post-dose; Days 3, 4, 5, 6, 7, 8, and 9: pre-dose and 5 min post-dose; Day 10: pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, 6 h post-dose; 24 h, 48 h, 72 h, 96 h and 120 h post-Day 10 dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating tmax and t1/2
Ratio of accumulation factor (Rs) of GSK2269557 following single and repeat inhalations Day 1 of session 2 and day 10 of session 2 Rs is defined as AUC(0-24) of Session 2 at day10 divided by AUC(0-infinity) of Session 1
Session 2: Time to maximum observed plasma drug concentration (Tmax) of GSK2269557 following repeat dose administration Day 1: pre-dose, 5 min and 24 h post-dose; Day 2: 5 min post-dose; Days 3, 4, 5, 6, 7, 8, and 9: pre-dose and 5 min post-dose; Day 10: pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, 6 h post-dose; 24 h, 48 h, 72 h, 96 h and 120 h post-Day 10 dose Blood samples will be collected at pre-dose and at specific post dose time points for calculating tmax
Ratio of accumulation factor (Ro) of GSK2269557 following single and repeat inhalations Day 1 of session 2 and day 10 of session 2 Ro is defined as AUC(0-24) of Session 2 at day10 divided by AUC(0-24) of Session1
Ratio of accumulation factor (R[Cmax]) of GSK2269557 following single and repeat inhalations Day 1 of session 2 and day 10 of session 2 R\[Cmax\] is defined as Cmax of Session 2 at day10 divided by Cmax of Session 1
Ratio of accumulation factor (R[Ctrough]) of GSK2269557 following single and repeat inhalations Day 1 of session 2 and day 10 of session 2 R\[Ctrough\] is defined as Ctrough of Session 2 at day10 divided by C24 of Session 1
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
GSK Investigational Site
🇯🇵Fukuoka, Japan