AsthmaPhase 1NCT03045887

Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of GSK2292767 in Healthy Participants Who Smoke Cigarettes

A Phase 1 study testing GSK2292767 50 μg and GSK2292767 500 μg in people with Asthma, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Asthma
What is being tested?: GSK2292767 50 μg and GSK2292767 500 μg
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 38 participants
Where: 1 siteUnited Kingdom
Study dates: 6 Feb 2017to 16 Aug 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Participant must be 18 to 50 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 cardiac monitoring). A participant with a clinical abnormality or laboratory parameters outside the reference range expected for them and the population being studied may be included only if the Investigator believes that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcomes
Participants who are current daily cigarette smokers (manufactured and self-rolled). Must have smoked regularly in the 12-month period preceding the screening visit
Normal spirometry (FEV1 >=80% of predicted) at screening
Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 18 to 31 kg/square meter (m^2) (inclusive)
Male and female

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Male participants: A male participant must agree to use contraception as detailed in the protocol during the treatment period and for at least from the time of first dose of study medication until at least 55 (5x11) hours plus an additional 90 days after the last dose of study medication and refrain from donating sperm during this period. GSK2292767 has a predicted half-life of approximately 11 hours
Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP)
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol

Who cannot join

History or presence of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, 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
Alanine transaminase (ALT) >1.5xupper 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)
Average corrected QT interval by Fridericia's formula (QTcF) >450 milliseconds (msec) (based on triplicate ECGs)

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Participants who have asthma or a history of asthma (except in childhood and which has now remitted)
Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing. Specific concomitant medications listed in protocol may be allowed
Live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study
Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 56 days
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
Current enrolment or past participation within the last 90 days of exposure to any other clinical study involving an investigational study treatment or any other type of medical research
Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening
Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment
Positive pre-study drug/alcohol screen
Positive human immunodeficiency virus (HIV) antibody test
Regular use of known drugs of abuse
Regular alcohol consumption within 3 months prior to the study defined as: An average weekly intake of >14 units for males and females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits
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
Participants who are unable to produce a total weight of at least 100 milligrams (mg) of selected sputum during sputum induction at screening
Participants whose primary consumption of tobacco is via methods other than cigarettes (manufactured or self-rolled). Primary methods of tobacco consumption that are excluded include, but are not limited to pipes and cigars

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: A Single-centre, Double-blind (Sponsor Open), Placebo Controlled Two Part Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of GSK2292767 as a Dry Powder in Healthy Participants Who Smoke Cigarettes

This study is the first administration of GSK2292767 to humans. The study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and repeat inhaled doses of GSK2292767 in healthy smokers. This study is intended to provide sufficient confidence in the safety of the molecule and preliminary information on target engagement to allow progression to further repeat dose and proof of mechanism studies. This is a two part, single site, randomized, double-blind (sponsor open), placebo controlled study. Part A will consist of two 3-period interlocking cohorts to evaluate the safety, tolerability and pharmacokinetics of ascending single doses of GSK2292767 administered as a dry powder inhalation. Part B is planned to follow Part A and progression will be based on an acceptable safety, tolerability and pharmacokinetic profiles. Subjects will receive repeat doses of GSK2292767 once daily for 14 days during Part B.

Conditions: Asthma
Being tested: GSK2292767 50 μg, GSK2292767 500 μg, Placebo
Keywords: repeat dose, GSK2292767, smoke, tolerability, safety, dry powder inhalation, pharmacokinetics, single dose
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK2292767 50 μgDrug
GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation
GSK2292767 500 μgDrug
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
PlaceboDrug
Lactose as powder for inhalation

Study groups in NCT03045887
Study group	Role	What they receive
Part A Cohort 1: Placebo- GSK2292767 (GSK) 200 µg-GSK 1000 µg	Experimental	Subjects will receive an inhaled single dose of placebo in Period 1, GSK2292767 200 µg in Period 2, and GSK2292767 1000 µg in Period 3. There will be a washout of approximately 4 weeks between doses. Receives: Drug: GSK2292767 50 μg; Drug: GSK2292767 500 μg; Drug: Placebo
Part A Cohort 1: GSK 50 µg-Placebo-GSK 1000 µg	Experimental	Subjects will receive an inhaled single dose of GSK2292767 50 µg in Period 1, placebo in Period 2, and GSK2292767 1000 µg in Period 3. There will be a washout of approximately 4 weeks between doses. Receives: Drug: GSK2292767 50 μg; Drug: GSK2292767 500 μg; Drug: Placebo
Part A Cohort 1: GSK 50 µg- GSK 200 µg-Placebo	Experimental	Subjects will receive an inhaled single dose of GSK2292767 50 µg in Period 1, GSK2292767 200 µg in Period 2, and placebo in Period 3. There will be a washout of approximately 4 weeks between doses. Receives: Drug: GSK2292767 50 μg; Drug: Placebo
Part A Cohort 1: GSK 50 µg-GSK 200 µg-GSK 1000 µg	Experimental	Subjects will receive an inhaled single dose of GSK2292767 50 µg in Period 1, GSK2292767 200 µg in Period 2, and GSK2292767 1000 µg in Period 3. There will be a washout of approximately 4 weeks between doses. Receives: Drug: GSK2292767 50 μg; Drug: GSK2292767 500 μg
Part A Cohort 2: Placebo-GSK 500 µg-GSK 2000 µg	Experimental	Subjects will receive an inhaled single dose of placebo in Period 1, GSK2292767 500 µg in Period 2, and GSK2292767 2000 µg in Period 3. There will be a washout of approximately 4 weeks between doses. Receives: Drug: GSK2292767 500 μg; Drug: Placebo
Part A Cohort 2: GSK 100 µg-Placebo- GSK 2000 µg	Experimental	Subjects will receive an inhaled single dose of GSK2292767 100 µg in Period 1, placebo in Period 2, and GSK2292767 2000 µg in Period 3. There will be a washout of approximately 4 weeks between doses. Receives: Drug: GSK2292767 50 μg; Drug: GSK2292767 500 μg; Drug: Placebo
Part A Cohort 2: GSK 100 µg-GSK 500 µg-Placebo	Experimental	Subjects will receive an inhaled single dose of GSK2292767 100 µg in Period 1, GSK2292767 500 µg in Period 2 and placebo in Period 3. There will be a washout of approximately 4 weeks between doses. Receives: Drug: GSK2292767 50 μg; Drug: GSK2292767 500 μg; Drug: Placebo
Part A Cohort 2: GSK 100 µg-GSK 500 µg-GSK 2000 µg	Experimental	Subjects will receive an inhaled single dose of GSK2292767 100 µg in Period 1, GSK2292767 500 µg in Period 2, GSK2292767 2000 µg in Period 3. There will be a washout of approximately 4 weeks between doses. Receives: Drug: GSK2292767 50 μg; Drug: GSK2292767 500 μg
Part B: GSK	Experimental	Subjects will receive inhaled repeat dose of GSK2292767 2000 µg once daily for 14 days. Receives: Drug: GSK2292767 500 μg
Part B: Placebo	Experimental	Subjects will receive inhaled repeat dose of placebo once daily for 14 days. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants with 5 percent nSAEs and SAEs has been reported.
Measured: Up to 12 weeks
Part B: Number of Participants With Any AE and Any SAE
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants with 5 percent nSAEs and SAEs has been reported.
Measured: Up to 4 weeks
Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Blood pressure in part A was assessed in a semi supine position with a completely automated device. SBP and DBP measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Measured: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Part B: Change From Baseline in SBP and DBP
Blood pressure in part B were assessed in semi supine position with a completely automated device. SBP and DBP preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Measured: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Part A: Change From Baseline in Heart Rate
Heart rate in part A was assessed in a semi supine position with a completely automated device. Heart rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Measured: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Part B: Change From Baseline in Heart Rate
Heart rate in part B was assessed in a semi supine position with a completely automated device. Heart rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Measured: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Part A: Change From Baseline in Respiratory Rate
Respiratory rate in part A was assessed in a semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Measured: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Part B: Change From Baseline in Respiratory Rate
Respiratory rate in part B was assessed in a semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Measured: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Part A: Change From Baseline in Tympanic Temperature
Tympanic temperature in part A was assessed in semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Measured: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Part B: Change From Baseline in Tympanic Temperature
Tympanic temperature in part B was assessed in semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Measured: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1)
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured using spirometry at the indicated time. FEV1 measurements were repeated until three technically acceptable measurements (within 150 milliliter [mL] of each other) were made. Data for FEV1 for part A is presented here.
Measured: Day 1 (pre-dose and 1 hour)
Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1)
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured using spirometry at the indicated time. Existing spirometry equipment was used. FEV1 measurements were repeated until three technically acceptable measurements (within 150 mL of each other) were made. Data for FEV1 for part B is presented here.
Measured: Up to Day 14
Part A: Forced Vital Capacity (FVC)
FVC is a measure of lung function and is defined as total amount of air that can be exhaled during FEV1 test. FVC was planned to measured using spirometry. The FVC need to be normal at screening and is part of the Forced Expiratory ratio (FEV1/FVC) which should lie between 0.7-0.8 to indicate no chronic obstruction or restriction. The FVC was therefore only used at screening and requires no ongoing analysis during the study. All other indications of obstruction in the study, e.g. paradoxical bronchospasm was provided by the FEV1. The FVC therefore require no analysis.
Measured: Day 1 (pre-dose and 1 hour)
Part B: Forced Vital Capacity (FVC)
FVC is a measure of lung function and is defined as total amount of air that can be exhaled during FEV1 test. FVC was planned to measured using spirometry. The FVC need to be normal at screening and is part of the Forced Expiratory ratio (FEV1/FVC) which should lie between 0.7-0.8 to indicate no chronic obstruction or restriction. The FVC was therefore only used at screening and requires no ongoing analysis during the study. All other indications of obstruction in the study, e.g. paradoxical bronchospasm was provided by the FEV1. The FVC therefore require no analysis.
Measured: Day 1 (pre-dose and 1 hour)
Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities
Triplicate/Single 12-lead ECG was obtained using an automated ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTFc intervals. Number of participants with abnormal clinically significant and abnormal-not clinically significant values at any time post-Baseline is presented.
Measured: Day 1 of each treatment period
Part B: Number of Participants With ECG Abnormalities
Triplicate/Single 12-lead ECG was obtained using an automated ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTFc intervals. Number of participants with abnormal clinically significant and abnormal-not clinically significant values at any time post-Baseline is presented.
Measured: Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC)
Number of participants with clinical chemistry values that changed from normal to high or low in part A are presented. Chemistry parameters for which PCC values were identified were: Alkaline Phosphatase, Alanine Amino Transferase, aspartate aminotransferase, Total Bilirubin, calcium, glucose, potassium and Sodium.
Measured: 24 hours post-dose in each treatment period.
Part B: Number of Participants With Clinical Chemistry Values of PCC
Number of participants with clinical chemistry values that changed from normal to high or low in part B are presented. Chemistry parameters for which PCC values were identified were: Alkaline Phosphatase, Alanine Amino Transferase, aspartate aminotransferase, Total Bilirubin, calcium, glucose, potassium and Sodium. Only participants with data available at specified time points were analyzed (represented by n=X in category titles)
Measured: Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14
Part A: Number of Participants With Hematology Values of PCC
Number of participants with hematology parameters of PCC which shifted from normal to high in part A are presented. Hematology parameters for which PCC values were identified were: Hemoglobin, Hematocrit, Lymphocytes, Total Neutrophils, Platelet count and White Blood Cell (WBC) Count. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles)
Measured: 24 hours post-dose in each treatment period
Part B: Number of Participants With Hematology Values of PCC
Number of participants with hematology parameters of PCC which shifted from normal to high in part B are presented. Hematology parameters for which PCC values were identified were: Hemoglobin, Hematocrit, Lymphocytes, Total Neutrophils, Platelet count and WBC count
Measured: Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14

Secondary outcomes (12)

Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for AUC (0 to t), AUC (0 to 24) and AUC (0 to inf) of GSK2292767 for part A is presented. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). Pharmacokinetic population comprised of participants in the 'All participant' population for whom a pharmacokinetic sample was obtained and analyzed.
Measured: Pre-dose (5 minutes (min), 30 min, 45 min, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for AUC (0 to t), AUC (0 to 24) and AUC (0 to inf) of GSK2292767 for part B is presented. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Five min post dose concentrations on Days 2-13 were assumed to be the Cmax values. Data for Cmax of GSK2292767 for part A is presented. Cmax is defined as maximum observed plasma concentration of GSK2292767.
Measured: Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Part B: Cmax of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Five minute post dose concentrations on Days 2-13 were assumed to be the Cmax values. Data for Cmax of GSK2292767 for part B is presented.
Measured: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Tmax of GSK2292767 for part A is presented.
Measured: Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Part B: Tmax of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Tmax of GSK2292767 for part B is presented.
Measured: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part A: Terminal Half-life (T1/2) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for T1/2 of GSK2292767 for part A is presented. T1/2 is defined as the time required for one half of the total amount of a particular substance in a biological system to be degraded by biological processes. Only those participants with data available at the specified time points were analyzed.
Measured: Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Part B: T1/2 of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for T1/2 of GSK2292767 for part B is presented. T1/2 was defined as the time required for one half of the total amount of a particular substance in a biological system to be degraded by biological processes. Only those participants with data available at the specified time points were analyzed.
Measured: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part A: Trough Concentrations (Ctau) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Ctau of GSK2292767 for part A is presented. Ctau is defined as the lowest concentration reached by a drug before the next dose is administered.
Measured: 24 hr post dose in each of the 3 treatment periods
Part B: Ctau of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Ctau of GSK2292767 for part B is presented. Ctau is defined as the lowest concentration reached by a drug before the next dose is administered. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part B: Concentration of GSK2292767 in Bronchoalveolar Lavage (BAL)
BAL samples were collected by bronchoscopy.
Measured: Day 15
Part B: Concentration of GSK2292767 in Lung Epithelial Lining Fluid (ELF)
ELF from the lung was extracted from BAL samples. ELF drug concentration was calculated as BAL fluid drug concentration multiplied by dilution factor where dilution factor = Plasma urea (pre-bronchoscopy) divided by BAL urea. NA indicates data not available. Only participants with data available at specified time points were analyzed (represented by n=X in category titles).
Measured: Day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Feb 201716 Aug 2017

First posted8 Feb 2017 (estimated)
Study start6 Feb 2017
Primary completion11 Aug 2017
Study completion16 Aug 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for AsthmaStudies 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: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03045887
Sponsor's protocol ID: 202062
Other IDs: 2016-003188-21, 2016
Status last verified: Jul 2019
First submitted: 3 Feb 2017
Last updated: 24 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

Begg M, Edwards CD, Hamblin JN, Pefani E, Wilson R, Gilbert J, Vitulli G, Mallett D, Morrell J, Hingle MI, Uddin S, Ehtesham F, Marotti M, Harrell A, Newman CF, Fernando D, Clark J, Cahn A, Hessel EM. Translation of Inhaled Drug Optimization Strategies into Clinical Pharmacokinetics and Pharmacodynamics Using GSK2292767A, a Novel Inhaled Phosphoinositide 3-Kinase delta Inhibitor. J Pharmacol Exp Ther. 2019 Jun;369(3):443-453. doi: 10.1124/jpet.119.257311. Epub 2019 Apr 2.
PubMed 30940692

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

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Questions to ask the study team

What is the study trying to find out?
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Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
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Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single-centre, Double-blind (Sponsor Open), Placebo Controlled Two Part Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of GSK2292767 as a Dry Powder in Healthy Participants Who Smoke Cigarettes
ClinicalTrials.gov ID: NCT03045887
Acronym / sponsor ID: 202062
Conditions: Asthma
Keywords: repeat dose, GSK2292767, smoke, tolerability, safety, dry powder inhalation, pharmacokinetics, single dose
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 38 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 6 Feb 2017 (actual)
Primary completion: 11 Aug 2017 (actual)
Study completion: 16 Aug 2017 (actual)
First posted: 8 Feb 2017 (estimated)
Results: Posted 28 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 10

Arm	Type	Receives
Part A Cohort 1: Placebo- GSK2292767 (GSK) 200 µg-GSK 1000 µg	Experimental	Drug: GSK2292767 50 μg, Drug: GSK2292767 500 μg, Drug: PlaceboSubjects will receive an inhaled single dose of placebo in Period 1, GSK2292767 200 µg in Period 2, and GSK2292767 1000 µg in Period 3. There will be a washout of approximately 4 weeks between doses.
Part A Cohort 1: GSK 50 µg-Placebo-GSK 1000 µg	Experimental	Drug: GSK2292767 50 μg, Drug: GSK2292767 500 μg, Drug: PlaceboSubjects will receive an inhaled single dose of GSK2292767 50 µg in Period 1, placebo in Period 2, and GSK2292767 1000 µg in Period 3. There will be a washout of approximately 4 weeks between doses.
Part A Cohort 1: GSK 50 µg- GSK 200 µg-Placebo	Experimental	Drug: GSK2292767 50 μg, Drug: PlaceboSubjects will receive an inhaled single dose of GSK2292767 50 µg in Period 1, GSK2292767 200 µg in Period 2, and placebo in Period 3. There will be a washout of approximately 4 weeks between doses.
Part A Cohort 1: GSK 50 µg-GSK 200 µg-GSK 1000 µg	Experimental	Drug: GSK2292767 50 μg, Drug: GSK2292767 500 μgSubjects will receive an inhaled single dose of GSK2292767 50 µg in Period 1, GSK2292767 200 µg in Period 2, and GSK2292767 1000 µg in Period 3. There will be a washout of approximately 4 weeks between doses.
Part A Cohort 2: Placebo-GSK 500 µg-GSK 2000 µg	Experimental	Drug: GSK2292767 500 μg, Drug: PlaceboSubjects will receive an inhaled single dose of placebo in Period 1, GSK2292767 500 µg in Period 2, and GSK2292767 2000 µg in Period 3. There will be a washout of approximately 4 weeks between doses.
Part A Cohort 2: GSK 100 µg-Placebo- GSK 2000 µg	Experimental	Drug: GSK2292767 50 μg, Drug: GSK2292767 500 μg, Drug: PlaceboSubjects will receive an inhaled single dose of GSK2292767 100 µg in Period 1, placebo in Period 2, and GSK2292767 2000 µg in Period 3. There will be a washout of approximately 4 weeks between doses.
Part A Cohort 2: GSK 100 µg-GSK 500 µg-Placebo	Experimental	Drug: GSK2292767 50 μg, Drug: GSK2292767 500 μg, Drug: PlaceboSubjects will receive an inhaled single dose of GSK2292767 100 µg in Period 1, GSK2292767 500 µg in Period 2 and placebo in Period 3. There will be a washout of approximately 4 weeks between doses.
Part A Cohort 2: GSK 100 µg-GSK 500 µg-GSK 2000 µg	Experimental	Drug: GSK2292767 50 μg, Drug: GSK2292767 500 μgSubjects will receive an inhaled single dose of GSK2292767 100 µg in Period 1, GSK2292767 500 µg in Period 2, GSK2292767 2000 µg in Period 3. There will be a washout of approximately 4 weeks between doses.
Part B: GSK	Experimental	Drug: GSK2292767 500 μgSubjects will receive inhaled repeat dose of GSK2292767 2000 µg once daily for 14 days.
Part B: Placebo	Experimental	Drug: PlaceboSubjects will receive inhaled repeat dose of placebo once daily for 14 days.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

Participant must be 18 to 50 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 cardiac monitoring). A participant with a clinical abnormality or laboratory parameters outside the reference range expected for them and the population being studied may be included only if the Investigator believes that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcomes
Participants who are current daily cigarette smokers (manufactured and self-rolled). Must have smoked regularly in the 12-month period preceding the screening visit
Normal spirometry (FEV1 >=80% of predicted) at screening
Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 18 to 31 kg/square meter (m^2) (inclusive)

Key exclusion criteria (21 listed)

History or presence of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, 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
Alanine transaminase (ALT) >1.5xupper 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
GSK2292767 50 μgGSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation	Drug	Part A Cohort 1: GSK 50 µg- GSK 200 µg-Placebo, Part A Cohort 1: GSK 50 µg-GSK 200 µg-GSK 1000 µg, Part A Cohort 1: GSK 50 µg-Placebo-GSK 1000 µg, Part A Cohort 1: Placebo- GSK2292767 (GSK) 200 µg-GSK 1000 µg, Part A Cohort 2: GSK 100 µg-GSK 500 µg-GSK 2000 µg, Part A Cohort 2: GSK 100 µg-GSK 500 µg-Placebo, Part A Cohort 2: GSK 100 µg-Placebo- GSK 2000 µg
GSK2292767 500 μgGSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation	Drug	Part A Cohort 1: GSK 50 µg-GSK 200 µg-GSK 1000 µg, Part A Cohort 1: GSK 50 µg-Placebo-GSK 1000 µg, Part A Cohort 1: Placebo- GSK2292767 (GSK) 200 µg-GSK 1000 µg, Part A Cohort 2: GSK 100 µg-GSK 500 µg-GSK 2000 µg, Part A Cohort 2: GSK 100 µg-GSK 500 µg-Placebo, Part A Cohort 2: GSK 100 µg-Placebo- GSK 2000 µg, Part A Cohort 2: Placebo-GSK 500 µg-GSK 2000 µg, Part B: GSK
PlaceboLactose as powder for inhalation	Drug	Part A Cohort 1: GSK 50 µg- GSK 200 µg-Placebo, Part A Cohort 1: GSK 50 µg-Placebo-GSK 1000 µg, Part A Cohort 1: Placebo- GSK2292767 (GSK) 200 µg-GSK 1000 µg, Part A Cohort 2: GSK 100 µg-GSK 500 µg-Placebo, Part A Cohort 2: GSK 100 µg-Placebo- GSK 2000 µg, Part A Cohort 2: Placebo-GSK 500 µg-GSK 2000 µg, Part B: Placebo

Primary outcome

Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE)
Time frame: Up to 12 weeks
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants with 5 percent nSAEs and SAEs has been reported.
Part B: Number of Participants With Any AE and Any SAE
Time frame: Up to 4 weeks
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants with 5 percent nSAEs and SAEs has been reported.
Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Blood pressure in part A was assessed in a semi supine position with a completely automated device. SBP and DBP measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Part B: Change From Baseline in SBP and DBP
Time frame: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Blood pressure in part B were assessed in semi supine position with a completely automated device. SBP and DBP preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Part A: Change From Baseline in Heart Rate
Time frame: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Heart rate in part A was assessed in a semi supine position with a completely automated device. Heart rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Part B: Change From Baseline in Heart Rate
Time frame: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Heart rate in part B was assessed in a semi supine position with a completely automated device. Heart rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Part A: Change From Baseline in Respiratory Rate
Time frame: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Respiratory rate in part A was assessed in a semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Part B: Change From Baseline in Respiratory Rate
Time frame: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Respiratory rate in part B was assessed in a semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Part A: Change From Baseline in Tympanic Temperature
Time frame: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Tympanic temperature in part A was assessed in semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Part B: Change From Baseline in Tympanic Temperature
Time frame: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Tympanic temperature in part B was assessed in semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1)
Time frame: Day 1 (pre-dose and 1 hour)
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured using spirometry at the indicated time. FEV1 measurements were repeated until three technically acceptable measurements (within 150 milliliter [mL] of each other) were made. Data for FEV1 for part A is presented here.
Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1)
Time frame: Up to Day 14
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured using spirometry at the indicated time. Existing spirometry equipment was used. FEV1 measurements were repeated until three technically acceptable measurements (within 150 mL of each other) were made. Data for FEV1 for part B is presented here.
Part A: Forced Vital Capacity (FVC)
Time frame: Day 1 (pre-dose and 1 hour)
FVC is a measure of lung function and is defined as total amount of air that can be exhaled during FEV1 test. FVC was planned to measured using spirometry. The FVC need to be normal at screening and is part of the Forced Expiratory ratio (FEV1/FVC) which should lie between 0.7-0.8 to indicate no chronic obstruction or restriction. The FVC was therefore only used at screening and requires no ongoing analysis during the study. All other indications of obstruction in the study, e.g. paradoxical bronchospasm was provided by the FEV1. The FVC therefore require no analysis.
Part B: Forced Vital Capacity (FVC)
Time frame: Day 1 (pre-dose and 1 hour)
FVC is a measure of lung function and is defined as total amount of air that can be exhaled during FEV1 test. FVC was planned to measured using spirometry. The FVC need to be normal at screening and is part of the Forced Expiratory ratio (FEV1/FVC) which should lie between 0.7-0.8 to indicate no chronic obstruction or restriction. The FVC was therefore only used at screening and requires no ongoing analysis during the study. All other indications of obstruction in the study, e.g. paradoxical bronchospasm was provided by the FEV1. The FVC therefore require no analysis.
Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities
Time frame: Day 1 of each treatment period
Triplicate/Single 12-lead ECG was obtained using an automated ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTFc intervals. Number of participants with abnormal clinically significant and abnormal-not clinically significant values at any time post-Baseline is presented.
Part B: Number of Participants With ECG Abnormalities
Time frame: Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Triplicate/Single 12-lead ECG was obtained using an automated ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTFc intervals. Number of participants with abnormal clinically significant and abnormal-not clinically significant values at any time post-Baseline is presented.
Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC)
Time frame: 24 hours post-dose in each treatment period.
Number of participants with clinical chemistry values that changed from normal to high or low in part A are presented. Chemistry parameters for which PCC values were identified were: Alkaline Phosphatase, Alanine Amino Transferase, aspartate aminotransferase, Total Bilirubin, calcium, glucose, potassium and Sodium.
Part B: Number of Participants With Clinical Chemistry Values of PCC
Time frame: Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14
Number of participants with clinical chemistry values that changed from normal to high or low in part B are presented. Chemistry parameters for which PCC values were identified were: Alkaline Phosphatase, Alanine Amino Transferase, aspartate aminotransferase, Total Bilirubin, calcium, glucose, potassium and Sodium. Only participants with data available at specified time points were analyzed (represented by n=X in category titles)
Part A: Number of Participants With Hematology Values of PCC
Time frame: 24 hours post-dose in each treatment period
Number of participants with hematology parameters of PCC which shifted from normal to high in part A are presented. Hematology parameters for which PCC values were identified were: Hemoglobin, Hematocrit, Lymphocytes, Total Neutrophils, Platelet count and White Blood Cell (WBC) Count. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles)
Part B: Number of Participants With Hematology Values of PCC
Time frame: Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14
Number of participants with hematology parameters of PCC which shifted from normal to high in part B are presented. Hematology parameters for which PCC values were identified were: Hemoglobin, Hematocrit, Lymphocytes, Total Neutrophils, Platelet count and WBC count

12 secondary outcomes

Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767
Time frame: Pre-dose (5 minutes (min), 30 min, 45 min, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767
Time frame: Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Part B: Cmax of GSK2292767
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767
Time frame: Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Part B: Tmax of GSK2292767
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part A: Terminal Half-life (T1/2) of GSK2292767
Time frame: Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Part B: T1/2 of GSK2292767
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part A: Trough Concentrations (Ctau) of GSK2292767
Time frame: 24 hr post dose in each of the 3 treatment periods
Part B: Ctau of GSK2292767
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Part B: Concentration of GSK2292767 in Bronchoalveolar Lavage (BAL)
Time frame: Day 15
Part B: Concentration of GSK2292767 in Lung Epithelial Lining Fluid (ELF)
Time frame: Day 15

Results and safety

Results posted to the registry on 28 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A: Placebo/200 µg GSK2292767/1000 µg GSK2292767	7	7
Part A:50 µg GSK2292767/Placebo/1000 µg GSK2292767	4	4
Part A:50 µg GSK2292767/200 µg GSK2292767/Placebo	5	5
Part A:50 µg GSK2292767/200 µg GSK2292767/1000 µg GSK2292767	5	5
Part A:Placebo/500 µg GSK2292767/2000 µg GSK2292767	4	4
Part A:100 µg GSK2292767/Placebo/2000 µg GSK2292767	4	4
Part A:100 µg GSK2292767/500 µg GSK2292767/Placebo	4	4
Part A:100 µg GSK2292767/500 µg GSK2292767/2000 µg GSK2292767	4	4
Part B:Placebo	0	0
Part B:GSK2292767 2000 µg OD	0	0

Primary outcome: Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE)

Time frame: Up to 12 weeks. Count of participants. Unit: Participants

Measure	Placebo n = 23	50 µg OD n = 12	100 µg OD n = 12	200 µg OD n = 13	500 µg OD n = 12	1000 µg OD n = 9	2000 µg OD n = 12
nSAE	6	9	6	7	6	4	5
SAE	0	0	0	0	0	0	0

Population analysed: Safety Population comprised of all randomized participants who took at least 1 dose of study treatment.

Primary outcome: Part B: Number of Participants With Any AE and Any SAE

Time frame: Up to 4 weeks. Count of participants. Unit: Participants

Measure	Placebo n = 3	2000 µg OD n = 9
nSAE	3	8
SAE	0	0

Population analysed: Safety Population

Primary outcome: Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Time frame: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period. Mean (Standard Deviation). Unit: Millimeters of mercury

Measure	Placebo n = 23	50 µg OD n = 12	100 µg OD n = 12	200 µg OD n = 13	500 µg OD n = 12	1000 µg OD n = 9	2000 µg OD n = 12
DBP, 30 min	0.3 (6.66)	2.0 (6.48)	2.4 (4.91)	2.0 (5.23)	2.5 (6.20)	-1.6 (5.36)	1.9 (3.58)
DBP, 1 hour	0.8 (7.02)	3.1 (4.98)	3.8 (4.65)	1.2 (3.63)	4.1 (4.44)	-0.9 (7.72)	0.8 (5.04)
DBP, 6 hour	0.1 (5.48)	0.3 (7.41)	1.8 (3.84)	1.9 (7.04)	3.2 (6.22)	-2.0 (2.83)	3.1 (7.93)
DBP, 12 hour	2.3 (6.36)	3.1 (6.72)	2.9 (3.45)	4.0 (7.92)	2.3 (6.41)	0.7 (4.39)	3.1 (7.76)
DBP, 24 hour	-1.3 (6.81)	0.6 (6.32)	1.5 (3.90)	3.6 (8.03)	3.6 (4.21)	-2.9 (5.62)	-0.1 (5.12)
SBP, 30 min	-3.2 (6.28)	-0.2 (5.06)	-3.9 (9.67)	0.8 (5.16)	-2.3 (6.20)	-6.1 (4.73)	-3.3 (5.85)
SBP, 1 hour	-3.4 (7.72)	-1.5 (4.74)	-5.6 (8.07)	-3.4 (7.01)	-2.2 (6.53)	-7.1 (9.06)	-3.9 (8.38)
SBP, 6 hour	1.3 (8.79)	0.7 (8.23)	-3.8 (9.03)	4.5 (7.92)	2.8 (6.34)	-0.3 (7.48)	-0.8 (5.86)

Population analysed: Safety Population

Primary outcome: Part B: Change From Baseline in SBP and DBP

Time frame: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14. Mean (Standard Deviation). Unit: Millimeters of mercury

Measure	Placebo n = 3	2000 µg OD n = 9
DBP, Day 2, pre-dose	-6.0 (10.15)	-3.0 (4.72)
DBP, Day 3, pre-dose	-8.3 (9.45)	-1.3 (5.85)
DBP, Day 4, pre-dose	-7.3 (12.10)	-3.4 (4.90)
DBP, Day 5, pre-dose	-10.7 (11.72)	-2.2 (5.09)
DBP, Day 6, pre-dose	-7.7 (10.02)	-3.7 (4.72)
DBP, Day 7, pre-dose	-8.3 (9.45)	-2.3 (3.57)
DBP, Day 8, pre-dose	-5.7 (12.42)	-4.3 (3.91)
DBP, Day 9, pre-dose	-6.3 (11.93)	-2.8 (4.02)

Population analysed: Safety Population

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: nSAEs and SAEs were collected from start of study treatment up to 16 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: Placebo	0 of 23 (0%)	6 of 23 (26.1%)	0 of 23
Part A: 50 µg OD	0 of 12 (0%)	9 of 12 (75%)	0 of 12
Part A: 100 µg OD	0 of 12 (0%)	6 of 12 (50%)	0 of 12
Part A: 200 µg OD	0 of 13 (0%)	7 of 13 (53.8%)	0 of 13
Part A: 500 µg OD	0 of 12 (0%)	6 of 12 (50%)	0 of 12
Part A: 1000 µg OD	0 of 9 (0%)	4 of 9 (44.4%)	0 of 9
Part A: 2000 µg OD	0 of 12 (0%)	5 of 12 (41.7%)	0 of 12
Part B: Placebo	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Part B: 2000ug OD	0 of 9 (0%)	8 of 9 (88.9%)	0 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 30940692Begg M, Edwards CD, Hamblin JN, Pefani E, Wilson R, Gilbert J, Vitulli G, Mallett D, Morrell J, Hingle MI, Uddin S, Ehtesham F, Marotti M, Harrell A, Newman CF, Fernando D, Clark J, Cahn A, Hessel EM. Translation of Inhaled Drug Optimization Strategies into Clinical Pharmacokinetics and Pharmacodynamics Using GSK2292767A, a Novel Inhaled Phosphoinositide 3-Kinase delta Inhibitor. J Pharmacol Exp Ther. 2019 Jun;369(3):443-453. doi: 10.1124/jpet.119.257311. Epub 2019 Apr 2.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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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 (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

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 GSK2292767 50 μg and GSK2292767 500 μg in people with Asthma, run by GlaxoSmithKline at 1 site in United Kingdom.

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 9 inclusion and 21 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 24 Jul 2019. 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 United Kingdom. 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. 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?

Yes. Results are posted in the registry (first posted 28 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) (time frame: Up to 12 weeks). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03045887, which also lists 1 linked publication.

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 24 Jul 2019.