Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
pharmacokinetics, GSK2269557, Dry powder Inhaler (DPI), tolerability, safety, ELLIPTA
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.
Interventions
GSK2269557 ELLIPTA DPI contains GSK2269557 blended with lactose and magnesium stearate. This will be supplied in two strength of 100 mcg per blister and 500 mcg per blister.
Placebo ELLIPTA DPI contains lactose
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 20 to 64 years of age inclusive, at the time of signing the informed consent. * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, 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 that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Normal spirometry (forced expiratory volume in 1 second \>=80% of predicted) at Screening. * Body weight \>=50 kilograms (kg) and body mass index (BMI) within the range 18.5 to 24.9 kg/square meter (m\^2) (inclusive). * Japanese Male: A male participant must agree to use contraception of this protocol during the treatment period and until follow up visit. * Capable of giving signed informed consent as described in restrictions listed in the informed consent form (ICF).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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: 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: 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: 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: 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 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 |
| 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: 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 |
| 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 (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 (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 |
| 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 |
Countries
Japan
Outcome results
None listed