Pulmonary Disease, Chronic ObstructivePhase 1NCT02972905
Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2269557 to Japanese Healthy Subjects
A Phase 1 study testing GSK2269557 ELLIPTA DPI in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in Japan.
Trial 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). Read more about this study
- Who is it for?
- Ages 20 to 64 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- GSK2269557 ELLIPTA DPI
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteJapan
- Study dates
- Oct 2016to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 64 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- GSK2269557 ELLIPTA DPI, Placebo ELLIPTA DPI
- Keywords
- pharmacokinetics, GSK2269557, Dry powder Inhaler (DPI), tolerability, safety, ELLIPTA
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2269557 ELLIPTA DPIDrug
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 DPIDrug
Placebo ELLIPTA DPI contains lactose
| Study group | Role | What they receive |
|---|---|---|
| Session 1: Placebo | Placebo comparator | 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. Receives: Drug: Placebo ELLIPTA DPI |
| Session 1: GSK2269557 200 mcg | Experimental | 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. Receives: Drug: GSK2269557 ELLIPTA DPI |
| Session 1: GSK2269557 500 mcg | Experimental | 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. Receives: Drug: GSK2269557 ELLIPTA DPI |
| Session 1: GSK2269557 700 mcg | Experimental | 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. Receives: Drug: GSK2269557 ELLIPTA DPI |
| Session 2: Placebo | Placebo comparator | 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. Receives: Drug: Placebo ELLIPTA DPI |
| Session 2: GSK2269557 200 mcg | Experimental | 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. Receives: Drug: GSK2269557 ELLIPTA DPI |
| Session 2: GSK2269557 500 mcg | Experimental | 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. Receives: Drug: GSK2269557 ELLIPTA DPI |
| Session 2: GSK2269557 700 mcg | Experimental | 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. Receives: Drug: GSK2269557 ELLIPTA DPI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with any adverse event(s) (AE) and serious adverse event(s) (SAE)
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.
Measured: Approximately up to 37 days
Session 1: Number of subjects having abnormal clinical laboratory parameters as a measure of safety
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)
Measured: Approximately up to 4 days
Session 2: Number of subjects having abnormal clinical laboratory parameters as a measure of safety
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
Measured: Approximately up to 22 days
Session 1:Number of subjects having abnormal hematology laboratory parameters as a measure of safety
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
Measured: Approximately up to 4 days
Session 2: Number of subjects having abnormal hematology laboratory parameters as a measure of safety
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
Measured: Approximately up to 22 days
Session 1: Number of subjects having abnormal urinalysis as a measure of safety
Urine samples will be collected to analyse specific gravity, pH, glucose, protein, blood, ketones, bilirubin, and urobilinogen for dipstick, and microscopic examination
Measured: Approximately up to 4 days
Session 2: Number of subjects having abnormal urinalysis as a measure of safety
Urine samples will be collected to analyse specific gravity, pH, glucose, protein, blood, ketones, bilirubin, and urobilinogen for dipstick, and microscopic examination
Measured: Approximately up to 22 days
Session 1: Body temperature assessment as a safety measure
Temperature will be recorded in a supine position after 5 minutes rest
Measured: Approximately up to 4 days
Session 2: Body temperature assessment as a safety measure
Temperature will be recorded in a supine position after 5 minutes rest
Measured: Approximately up to 22 days
Session 1: Blood pressure assessment as a safety measure
Systolic and diastolic blood pressure will be measured in a supine positon after 5 minutes rest
Measured: Approximately up to 4 days
Session 2: Blood pressure assessment as a safety measure
Systolic and diastolic blood pressure will be measured in a supine position after 5 minutes rest
Measured: Approximately up to 22 days
Session 1: Measurement of pulse rate as a safety measure
Pulse rate will be measured in a supine position after 5 minutes rest
Measured: Approximately up to 4 days
Session 2: Measurement of pulse rate as a safety measure
Pulse rate will be measured in a supine position after 5 minutes rest
Measured: Approximately up to 22 days
Session 1: Electrocardiogram (ECG) assessment as a measure of safety.
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.
Measured: Approximately up to 4 days
Session 2: ECG assessment as a measure of safety.
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.
Measured: Approximately up to 22 days
Session 1: Spirometry assessment as a safety measure
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.
Measured: Approximately up to 4 days
Session 2: Spirometry assessment as a safety measure
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.
Measured: Approximately up to 22 days
Session 1: Area under the plasma concentration curve (AUC) from time zero to the time of last quantifiable concentration [AUC(0-t)]
Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC [0-t]
Measured: Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72hours (h) post-dose
Session 1: AUC from time zero to 24 hours post dose [AUC(0-24)] of GSK2269557 following a single dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC[0-24]
Measured: Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
Session 1: AUC from time zero to infinity [AUC(0-infinity)] of GSK2269557 following a single dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC (0-infinity).
Measured: Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
Session 2: AUC from time zero to the time of last quantifiable concentration [AUC(0-t)] of GSK2269557 following repeat dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC [0-t]
Measured: 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
Session 2: AUC from time zero to 24 hours post dose [AUC(0-24)] of GSK2269557 following repeat dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC[0-24]
Measured: 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
Session 2: AUC from time zero to infinity [AUC(0-infinity)] of GSK2269557 following repeat dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC (0-infinity)
Measured: 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
Session 1: Trough observed plasma drug concentration (Ctrough) of GSK2269557 following a single dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating Ctrough
Measured: Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
Session 1: Maximum observed plasma concentration (Cmax) of GSK2269557 following a single dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax
Measured: Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
Session 1: Maximum/trough observed plasma drug concentration (Cmax/Ctrough) of GSK2269557 following a single dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax/Ctrough
Measured: Pre-dose, 5, 15, 30 minutes (min), 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
Session 2: Trough observed plasma drug concentration (Ctrough) of GSK2269557 following repeat dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating Ctrough
Measured: 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
Session 2: Maximum observed plasma concentration (Cmax) of GSK2269557 following repeat dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax
Measured: 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
Session 2: Maximum/trough observed plasma drug concentration (Cmax/Ctrough) of GSK2269557 following repeat dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax/Ctrough
Measured: 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
Session 1: Time to maximum observed plasma drug concentration (Tmax) of GSK2269557 following a single dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating tmax
Measured: Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
Session 1: Terminal half-life (t1/2) of GSK2269557 following a single dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating t1/2
Measured: Pre-dose, 5, 15, 30 min, 1, 2 , 4 , 6, 12, 24, 36, 48, and 72h post-dose
Session 2: Time to maximum observed plasma drug concentration (Tmax) of GSK2269557 following repeat dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating tmax
Measured: 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
Session 2: Terminal half-life (t1/2) of GSK2269557 following repeat dose administration
Blood samples will be collected at pre-dose and at specific post dose time points for calculating tmax and t1/2
Measured: 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
Ratio of accumulation factor (Ro) of GSK2269557 following single and repeat inhalations
Ro is defined as AUC(0-24) of Session 2 at day10 divided by AUC(0-24) of Session1
Measured: Day 1 of session 2 and day 10 of session 2
Ratio of accumulation factor (Rs) of GSK2269557 following single and repeat inhalations
Rs is defined as AUC(0-24) of Session 2 at day10 divided by AUC(0-infinity) of Session 1
Measured: Day 1 of session 2 and day 10 of session 2
Ratio of accumulation factor (R[Cmax]) of GSK2269557 following single and repeat inhalations
R[Cmax] is defined as Cmax of Session 2 at day10 divided by Cmax of Session 1
Measured: Day 1 of session 2 and day 10 of session 2
Ratio of accumulation factor (R[Ctrough]) of GSK2269557 following single and repeat inhalations
R[Ctrough] is defined as Ctrough of Session 2 at day10 divided by C24 of Session 1
Measured: Day 1 of session 2 and day 10 of session 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2016 (estimated)
- Study startOct 2016
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02972905
- Sponsor's protocol ID
- 205759
- Status last verified
- Jan 2017
- First submitted
- 14 Oct 2016
- Last updated
- 18 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02972905
- Acronym / sponsor ID
- 205759
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- pharmacokinetics, GSK2269557, Dry powder Inhaler (DPI), tolerability, safety, ELLIPTA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Oct 2016
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 25 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Session 1: Placebo | Placebo comparator | Drug: Placebo ELLIPTA DPISubjects 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 | Experimental | Drug: GSK2269557 ELLIPTA DPISubjects 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 | Experimental | Drug: GSK2269557 ELLIPTA DPISubjects 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 | Experimental | Drug: GSK2269557 ELLIPTA DPISubjects 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 comparator | Drug: Placebo ELLIPTA DPISubjects 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 | Experimental | Drug: GSK2269557 ELLIPTA DPISubjects 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 | Experimental | Drug: GSK2269557 ELLIPTA DPISubjects 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 | Experimental | Drug: GSK2269557 ELLIPTA DPISubjects 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. |
Who may qualify
- Ages
- 20 to 64 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2269557 ELLIPTA DPIGSK2269557 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. | Drug | Session 1: GSK2269557 200 mcg, Session 1: GSK2269557 500 mcg, Session 1: GSK2269557 700 mcg, Session 2: GSK2269557 200 mcg, Session 2: GSK2269557 500 mcg, Session 2: GSK2269557 700 mcg |
| Placebo ELLIPTA DPIPlacebo ELLIPTA DPI contains lactose | Drug | Session 1: Placebo, Session 2: Placebo |
Primary outcome
Number of subjects with any adverse event(s) (AE) and serious adverse event(s) (SAE)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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)]
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK2269557 ELLIPTA DPI in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects with any adverse event(s) (AE) and serious adverse event(s) (SAE) (time frame: Approximately up to 37 days). The study lists 37 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2017.