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

July 10, 2019 updated by: GlaxoSmithKline

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
38

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Cambridge, United Kingdom, CB2 2GG
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

    • 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

Exclusion Criteria:

  • 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)
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part A Cohort 1: Placebo- GSK2292767 (GSK) 200 µg-GSK 1000 µg
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.
Drug: GSK2292767 50 μg
GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: GSK2292767 500 μg
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: Placebo
Lactose as powder for inhalation
Experimental: Part A Cohort 1: GSK 50 µg-Placebo-GSK 1000 µg
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.
Drug: GSK2292767 50 μg
GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: GSK2292767 500 μg
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: Placebo
Lactose as powder for inhalation
Experimental: Part A Cohort 1: GSK 50 µg- GSK 200 µg-Placebo
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.
Drug: GSK2292767 50 μg
GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: Placebo
Lactose as powder for inhalation
Experimental: Part A Cohort 1: GSK 50 µg-GSK 200 µg-GSK 1000 µg
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.
Drug: GSK2292767 50 μg
GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: GSK2292767 500 μg
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Experimental: Part A Cohort 2: Placebo-GSK 500 µg-GSK 2000 µg
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.
Drug: GSK2292767 500 μg
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: Placebo
Lactose as powder for inhalation
Experimental: Part A Cohort 2: GSK 100 µg-Placebo- GSK 2000 µg
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.
Drug: GSK2292767 50 μg
GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: GSK2292767 500 μg
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: Placebo
Lactose as powder for inhalation
Experimental: Part A Cohort 2: GSK 100 µg-GSK 500 µg-Placebo
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.
Drug: GSK2292767 50 μg
GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: GSK2292767 500 μg
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: Placebo
Lactose as powder for inhalation
Experimental: Part A Cohort 2: GSK 100 µg-GSK 500 µg-GSK 2000 µg
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.
Drug: GSK2292767 50 μg
GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Drug: GSK2292767 500 μg
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Experimental: Part B: GSK
Subjects will receive inhaled repeat dose of GSK2292767 2000 µg once daily for 14 days.
Drug: GSK2292767 500 μg
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
Experimental: Part B: Placebo
Subjects will receive inhaled repeat dose of placebo once daily for 14 days.
Drug: Placebo
Lactose as powder for inhalation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Up to 12 weeks
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.
Up to 4 weeks
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.
Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
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.
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
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.
Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
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.
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
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.
Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
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.
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
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.
Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
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.
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)
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.
Day 1 (pre-dose and 1 hour)
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.
Up to Day 14
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.
Day 1 (pre-dose and 1 hour)
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.
Day 1 (pre-dose and 1 hour)
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.
Day 1 of each treatment period
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.
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)
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.
24 hours post-dose in each treatment period.
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)
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
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)
24 hours post-dose in each treatment period
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
Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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.
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
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).
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
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.
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
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.
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
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Tmax of GSK2292767 for part A is presented.
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
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Tmax of GSK2292767 for part B is presented.
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
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.
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
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.
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
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.
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
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).
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
BAL samples were collected by bronchoscopy.
Day 15
Part B: Concentration of GSK2292767 in Lung Epithelial Lining Fluid (ELF)
Time Frame: Day 15
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).
Day 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 6, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 11, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 16, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 3, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2017

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 8, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 24, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202062
  • 2016-003188-21 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD is available via the Clinical Study Data Request site (click on the link provided below)

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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