Clinical trial NCT02972905: Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2269557 to Japanese Healthy Subjects
Official title: A Single Center, Double-blind, Randomized, Placebo-controlled, Parallel, Single and Repeat, Dose-ascending Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK2269557 Administered Via the ELLIPTA™ Dry Powder Inhaler to Healthy Japanese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: pharmacokinetics
GSK2269557
Dry powder Inhaler (DPI)
tolerability
safety
ELLIPTA
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-11-25
Enrollment: 36
Sex: MALE
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

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 treatment; or interfering with the interpretation of data
* Abnormal blood pressure as determined by the investigator
* ALT \>1.5x upper limit of normal (ULN)
* Bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
* QTcF \>450 milliseconds (msec).
* Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing.
* History of donation of blood or blood products \>=400 milliliters (mL) within 3 months or \>=200 mL within 1 month prior to screening
* Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
* Current enrollment or past participation within the last 30 days before signing of consent in this clinical study involving an investigational study treatment or any other type of medical research
* The subject is positive Serological test for syphilis (rapid plasma reagin and Treponema pallidum), Human immunodeficiency virus (HIV) Antigen/Antibody, Hepatitis B surface antigen (HbsAg), Hepatitis C virus (HCV) antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody at screening.
* Positive pre-study drug screen
* Regular use of known drugs of abuse
* Regular alcohol consumption within 6 months prior to the study defined as: for an average weekly intake of \>14 units for males. One unit is equivalent to 350 ml of beer, 150 ml of wine or 45 ml of 80 proof distilled spirits
* Smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening
* Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study

Primary outcomes:
measure: Number of subjects with any adverse event(s) (AE) and serious adverse event(s) (SAE)
timeFrame: Approximately up to 37 days
measure: Session 1: Number of subjects having abnormal clinical laboratory parameters as a measure of safety
timeFrame: Approximately up to 4 days
measure: Session 2: Number of subjects having abnormal clinical laboratory parameters as a measure of safety
timeFrame: Approximately up to 22 days
measure: Session 1:Number of subjects having abnormal hematology laboratory parameters as a measure of safety
timeFrame: Approximately up to 4 days
measure: Session 2: Number of subjects having abnormal hematology laboratory parameters as a measure of safety
timeFrame: Approximately up to 22 days
measure: Session 1: Number of subjects having abnormal urinalysis as a measure of safety
timeFrame: Approximately up to 4 days
measure: Session 2: Number of subjects having abnormal urinalysis as a measure of safety
timeFrame: Approximately up to 22 days
measure: Session 1: Body temperature assessment as a safety measure
timeFrame: Approximately up to 4 days
measure: Session 2: Body temperature assessment as a safety measure
timeFrame: Approximately up to 22 days
measure: Session 1: Blood pressure assessment as a safety measure
timeFrame: Approximately up to 4 days
measure: Session 2: Blood pressure assessment as a safety measure
timeFrame: Approximately up to 22 days
measure: Session 1: Measurement of pulse rate as a safety measure
timeFrame: Approximately up to 4 days
measure: Session 2: Measurement of pulse rate as a safety measure
timeFrame: Approximately up to 22 days
measure: Session 1: Electrocardiogram (ECG) assessment as a measure of safety.
timeFrame: Approximately up to 4 days
measure: Session 2: ECG assessment as a measure of safety.
timeFrame: Approximately up to 22 days
measure: Session 1: Spirometry assessment as a safety measure
timeFrame: Approximately up to 4 days
measure: Session 2: Spirometry assessment as a safety measure
timeFrame: Approximately up to 22 days
measure: Session 1: Area under the plasma concentration curve (AUC) from time zero to the time of last quantifiable concentration [AUC(0-t)]
timeFrame: Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72hours (h) post-dose
measure: Session 1: AUC from time zero to 24 hours post dose [AUC(0-24)] of GSK2269557 following a single dose administration
timeFrame: Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
measure: Session 1: AUC from time zero to infinity [AUC(0-infinity)] of GSK2269557 following a single dose administration
timeFrame: Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
measure: Session 2: AUC from time zero to the time of last quantifiable concentration [AUC(0-t)] of GSK2269557 following repeat dose administration
timeFrame: 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
measure: Session 2: AUC from time zero to 24 hours post dose [AUC(0-24)] of GSK2269557 following repeat dose administration
timeFrame: 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
measure: Session 2: AUC from time zero to infinity [AUC(0-infinity)] of GSK2269557 following repeat dose administration
timeFrame: 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
measure: Session 1: Trough observed plasma drug concentration (Ctrough) of GSK2269557 following a single dose administration
timeFrame: Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
measure: Session 1: Maximum observed plasma concentration (Cmax) of GSK2269557 following a single dose administration
timeFrame: Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
measure: Session 1: Maximum/trough observed plasma drug concentration (Cmax/Ctrough) of GSK2269557 following a single dose administration
timeFrame: Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
measure: Session 2: Trough observed plasma drug concentration (Ctrough) of GSK2269557 following repeat dose administration
timeFrame: 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
measure: Session 2: Maximum observed plasma concentration (Cmax) of GSK2269557 following repeat dose administration
timeFrame: 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
measure: Session 2: Maximum/trough observed plasma drug concentration (Cmax/Ctrough) of GSK2269557 following repeat dose administration
timeFrame: 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
measure: Session 1: Time to maximum observed plasma drug concentration (Tmax) of GSK2269557 following a single dose administration
timeFrame: Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
measure: Session 1: Terminal half-life (t1/2) of GSK2269557 following a single dose administration
timeFrame: Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
measure: Session 2: Time to maximum observed plasma drug concentration (Tmax) of GSK2269557 following repeat dose administration
timeFrame: 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
measure: Session 2: Terminal half-life (t1/2) of GSK2269557 following repeat dose administration
timeFrame: 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
measure: Ratio of accumulation factor (Ro) of GSK2269557 following single and repeat inhalations
timeFrame: Day 1 of session 2 and day 10 of session 2
measure: Ratio of accumulation factor (Rs) of GSK2269557 following single and repeat inhalations
timeFrame: Day 1 of session 2 and day 10 of session 2
measure: Ratio of accumulation factor (R[Cmax]) of GSK2269557 following single and repeat inhalations
timeFrame: Day 1 of session 2 and day 10 of session 2
measure: Ratio of accumulation factor (R[Ctrough]) of GSK2269557 following single and repeat inhalations
timeFrame: Day 1 of session 2 and day 10 of session 2
Secondary outcomes:
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: