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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-003188-21 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2292767 50 μg | Drug | GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period |
| Part B: Change From Baseline in SBP and DBP |
| 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 | 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. |
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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
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:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | CB2 2GG | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30940692 | Background | 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. |
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IPD for this study will be made available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (click on the link provided below)
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.
Part A comprised of two cohorts, each of which consisted of 3 treatment periods with 4 treatment sequences. Out of 98 screened participants, 37 were randomized, 58 were screen failures and 3 were retained as reserve participants. In Part B, 12 participants were included, 11 of them were taken from Part A and 1 additional participant only for Part B
This is a two part, single site, randomized, double-blind (sponsor open), placebo controlled study in healthy smokers. Study was conducted in the United Kingdom.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: Placebo/200 µg GSK2292767/1000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 1 were administered a single dose of placebo in Period 1, 200 µg GSK2292767 in Period 2 and 1000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA Dry Powder Inhaler (DPI). There was a period of 4 weeks between doses for an individual participant. |
| FG001 | Part A:50 µg GSK2292767/Placebo/1000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 2 were administered a single dose of 50 µg GSK2292767 in Period 1, placebo in Period 2 and 1000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| FG002 | Part A:50 µg GSK2292767/200 µg GSK2292767/Placebo | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 3 were administered a single dose of 50 µg GSK2292767 in Period 1, 200 µg GSK2292767 in Period 2 and placebo in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| FG003 | Part A:50 µg GSK2292767/200 µg GSK2292767/1000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 4 were administered a single dose of 50 µg GSK2292767 in Period 1, 200 µg GSK2292767 in Period 2 and 1000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| FG004 | Part A:Placebo/500 µg GSK2292767/2000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 5 were administered a single dose of placebo in Period 1, 500 µg GSK2292767 in Period 2 and 2000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| FG005 | Part A:100 µg GSK2292767/Placebo/2000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 6 were administered a single dose of 100 ug GSK2292767 in Period 1, placebo in Period 2 and 2000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| FG006 | Part A:100 µg GSK2292767/500 µg GSK2292767/Placebo | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 7 were administered a single dose of 100 µg GSK2292767 in Period 1, 500 µg GSK2292767 in Period 2 and placebo in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| FG007 | Part A:100 µg GSK2292767/500 µg GSK2292767/2000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 8 were administered a single dose of 100 µg GSK2292767 in Period 1, 500 µg GSK2292767 in Period 2 and 2000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI . There was a period of 4 weeks between doses for an individual participant. |
| FG008 | Part B:Placebo | Participants were administered once daily dose of placebo for 14 days via inhalation route using ELLIPTA DPI |
| FG009 | Part B:GSK2292767 2000 µg OD | Participants were administered 2000 µg GSK2292767 once daily for 14 days via inhalation route using ELLIPTA DPI |
| Title | Milestones | Reasons Not Completed | ||||||||||||
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| Part A, Period (1 Day) |
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| Part A,Washout Period 1(4 Weeks) |
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| Part A, Period 2 (1 Day) |
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| Part A,Washout Period 2 (4 Weeks) |
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| Part A, Period 3 (1 Day) |
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| Part B (14 Days) |
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Data is presented for Part A and Part B. In Part B, 12 participants were included, 11 of them were taken from Part A and 1 additional participant only for Part B. Thus total number of participants included were 38 and not 49.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A:Placebo/200 µg GSK2292767/1000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 1 were administered a single dose of placebo in Period 1, 200 µg GSK2292767 in Period 2 and 1000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA Dry Powder Inhaler (DPI). There was a period of 4 weeks between doses for an individual participant. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | All enrolled participants have been confirmed by site to have been at least 18 years at the time of screening. One participants has a derived age of 17 due to the way in which their partial birthdate was imputed. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety Population comprised of all randomized participants who took at least 1 dose of study treatment. | Posted | Count of Participants | Participants | Up to 12 weeks |
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nSAEs and SAEs were collected from start of study treatment up to 16 weeks
nSAEs and SAEs were collected in Safety Population
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A: Placebo | Participants administered a single dose of placebo using ELLIPTA DPI via inhalation route. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rhythm idioventricular | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 5, 2017 | Apr 26, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 23, 2017 | Apr 26, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C000603799 | GSK2292767 |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| Part B: GSK | Experimental | Subjects will receive inhaled repeat dose of GSK2292767 2000 µg once daily for 14 days. |
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| Part B: Placebo | Experimental | Subjects will receive inhaled repeat dose of placebo once daily for 14 days. |
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| GSK2292767 500 μg | Drug | GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation |
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| Placebo | Drug | Lactose as powder for inhalation |
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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 | 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 | 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 | 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 | 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 | 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 | 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) | 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) | 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) | 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) | 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 | 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 | 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) | 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 | 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 | 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 | 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 |
| 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). | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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. | 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). | Day 15 |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | Part A:50 µg GSK2292767/Placebo/1000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 2 were administered a single dose of 50 µg GSK2292767 in Period 1, placebo in Period 2 and 1000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| BG002 | Part A:50 µg GSK2292767/200 µg GSK2292767/Placebo | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 3 were administered a single dose of 50 µg GSK2292767 in Period 1, 200 µg GSK2292767 in Period 2 and placebo in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| BG003 | Part A:50 µg GSK2292767/200 µg GSK2292767/1000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 4 were administered a single dose of 50 µg GSK2292767 in Period 1, 200 µg GSK2292767 in Period 2 and 1000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| BG004 | Part A:Placebo/500 µg GSK2292767/2000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 5 were administered a single dose of placebo in Period 1, 500 µg GSK2292767 in Period 2 and 2000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| BG005 | Part A:100 µg GSK2292767/Placebo/2000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 6 were administered a single dose of 100 ug GSK2292767 in Period 1, placebo in Period 2 and 2000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| BG006 | Part A:100 µg GSK2292767/500 µg GSK2292767/Placebo | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 7 were administered a single dose of 100 µg GSK2292767 in Period 1, 500 µg GSK2292767 in Period 2 and placebo in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. |
| BG007 | Part A:100 µg GSK2292767/500 µg GSK2292767/2000 µg GSK2292767 | Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 8 were administered a single dose of 100 µg GSK2292767 in Period 1, 500 µg GSK2292767 in Period 2 and 2000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI . There was a period of 4 weeks between doses for an individual participant. |
| BG008 | Part B: Placebo | Participants were administered once daily dose of placebo for 14 days via inhalation route using ELLIPTA DPI |
| BG009 | Part B: GSK2292767 2000 µg OD | Participants were administered 2000 µg GSK2292767 once daily for 14 days via inhalation route using ELLIPTA DPI |
| BG010 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
Participants administered a single dose of placebo using ELLIPTA DPI via inhalation route.
| OG001 | 50 µg OD | Participants administered a single dose of 50 µg GSK2292767 via inhalation route using ELLIPTA DPI |
| OG002 | 100 µg OD | Participants administered a single dose of 100 µg GSK2292767 via inhalation route using ELLIPTA DPI |
| OG003 | 200 µg OD | Participants administered a single dose of 200 µg GSK2292767 via inhalation route using ELLIPTA DPI |
| OG004 | 500 µg OD | Participants administered a single dose of 500 µg GSK2292767 via inhalation route using ELLIPTA DPI |
| OG005 | 1000 µg OD | Participants administered a single dose of 1000 µg GSK2292767 via inhalation route using ELLIPTA DPI |
| OG006 | 2000 µg OD | Participants administered a single dose of 2000 µg GSK2292767 via inhalation route using ELLIPTA DPI |
|
|
| Primary | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 4 weeks |
|
|
|
| Primary | 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. | Safety Population | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period |
|
|
|
| Primary | 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. | Safety Population | Posted | Mean | Standard Deviation | Millimeters of mercury | 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 |
|
|
|
| Primary | 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. | Safety Population | Posted | Mean | Standard Deviation | Beats per minute | Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period |
|
|
|
| Primary | 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. | Safety Population | Posted | Mean | Standard Deviation | Beats per minute | 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 |
|
|
|
| Primary | 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. | Safety Population | Posted | Median | Standard Deviation | Breaths per minute | Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period |
|
|
|
| Primary | 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. | Safety Population | Posted | Mean | Standard Deviation | Breaths per minute | 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 |
|
|
|
| Primary | 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. | Safety Population | Posted | Mean | Standard Deviation | Celsius | Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period |
|
|
|
| Primary | 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. | Safety Population | Posted | Mean | Standard Deviation | Celsius | 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 |
|
|
|
| Primary | 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. | Safety Population | Posted | Mean | Standard Deviation | Liters | Day 1 (pre-dose and 1 hour) |
|
|
|
| Primary | 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. | Safety Population | Posted | Mean | Standard Deviation | Liters | Up to Day 14 |
|
|
|
| Primary | 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. | Safety Population. Data was not collected for this outcome as FVC was used only at screening and no further analysis during the study was required. | Posted | Day 1 (pre-dose and 1 hour) |
|
|
| Primary | 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. | Safety Population. Data was not collected for this outcome as FVC was used only at screening and no further analysis during the study was required. | Posted | Day 1 (pre-dose and 1 hour) |
|
|
| Primary | 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. | Safety Population | Posted | Count of Participants | Participants | Day 1 of each treatment period |
|
|
|
| Primary | 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. | Safety Population | Posted | Count of Participants | Participants | 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 |
|
|
|
| Primary | 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. | Safety Population | Posted | Count of Participants | Participants | 24 hours post-dose in each treatment period. |
|
|
|
| Primary | 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) | Safety Population | Posted | Count of Participants | Participants | Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14 |
|
|
|
| Primary | 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) | Safety Population | Posted | Count of Participants | Participants | 24 hours post-dose in each treatment period |
|
|
|
| Primary | 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 | Safety Population | Posted | Count of Participants | Participants | Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14 |
|
|
|
| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picograms per milliliter | 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 |
|
|
|
|
| Secondary | 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). | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picograms per milliliter | 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 |
|
|
|
|
| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Picograms per milliliter | 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 |
|
|
|
|
| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Picograms per milliliter | 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 |
|
|
|
|
| Secondary | 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. | Pharmacokinetic Population | Posted | Median | Full Range | Hours | 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 |
|
|
|
| Secondary | 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. | Pharmacokinetic Population | Posted | Median | Full Range | Hours | 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 |
|
|
|
| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
|
|
|
| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
|
|
|
| Secondary | 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. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | Picograms per milliliter | 24 hr post dose in each of the 3 treatment periods |
|
|
|
| Secondary | 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). | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Pico grams per milliliter | 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 |
|
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|
|
| Secondary | Part B: Concentration of GSK2292767 in Bronchoalveolar Lavage (BAL) | BAL samples were collected by bronchoscopy. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Picograms per milliliter | Day 15 |
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|
|
| Secondary | 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). | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Picograms per milliliters | Day 15 |
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| 6 |
| 23 |
| EG001 | Part A: 50 µg OD | Participants administered a single dose of 50 µg GSK2292767 via inhalation route using ELLIPTA DPI | 0 | 12 | 0 | 12 | 9 | 12 |
| EG002 | Part A: 100 µg OD | Participants administered a single dose of 100 µg GSK2292767 via inhalation route using ELLIPTA DPI | 0 | 12 | 0 | 12 | 6 | 12 |
| EG003 | Part A: 200 µg OD | Participants administered a single dose of 200 µg GSK2292767 via inhalation route using ELLIPTA DPI | 0 | 13 | 0 | 13 | 7 | 13 |
| EG004 | Part A: 500 µg OD | Participants administered a single dose of 500 µg GSK2292767 via inhalation route using ELLIPTA DPI | 0 | 12 | 0 | 12 | 6 | 12 |
| EG005 | Part A: 1000 µg OD | Participants administered a single dose of 1000 µg GSK2292767 via inhalation route using ELLIPTA DPI | 0 | 9 | 0 | 9 | 4 | 9 |
| EG006 | Part A: 2000 µg OD | Participants administered a single dose of 2000 µg GSK2292767 via inhalation route using ELLIPTA DPI | 0 | 12 | 0 | 12 | 5 | 12 |
| EG007 | Part B: Placebo | Participants were administered once daily dose of placebo for 14 days via inhalation route using ELLIPTA DPI | 0 | 3 | 0 | 3 | 3 | 3 |
| EG008 | Part B: 2000ug OD | Participants were administered 2000 µg GSK2292767 once daily for 14 days via inhalation route using ELLIPTA DPI | 0 | 9 | 0 | 9 | 8 | 9 |
| Visual impairment | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lip ulceration | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Feeling cold | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Suffocation feeling | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Ear disorder | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
|
| Catheter site bruise | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Catheter site haematoma | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vessel puncture site bruise | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oropharyngeal candidiasis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Bronchoscopy abnormal | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Sputum abnormal | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Nasal obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| DBP, 1 hour |
|
| DBP, 6 hour |
|
| DBP, 12 hour |
|
| DBP, 24 hour |
|
| SBP, 30 min |
|
| SBP, 1 hour |
|
| SBP, 6 hour |
|
| SBP, 12 hour |
|
| SBP, 24 hour |
|
| DBP, Day 4, pre-dose |
|
| DBP, Day 5, pre-dose |
|
| DBP, Day 6, pre-dose |
|
| DBP, Day 7, pre-dose |
|
| DBP, Day 8, pre-dose |
|
| DBP, Day 9, pre-dose |
|
| DBP, Day 10, pre-dose |
|
| DBP, Day 11, pre-dose |
|
| DBP, Day 12, pre-dose |
|
| DBP, Day 13, pre-dose |
|
| DBP, Day 14, pre-dose |
|
| DBP, Day 14, 24 hours |
|
| SBP, Day 2, pre-dose |
|
| SBP, Day 3, pre-dose |
|
| SBP, Day 4, pre-dose |
|
| SBP, Day 5, pre-dose |
|
| SBP, Day 6, pre-dose |
|
| SBP, Day 7, pre-dose |
|
| SBP, Day 8, pre-dose |
|
| SBP, Day 9, pre-dose |
|
| SBP, Day 10, pre-dose |
|
| SBP, Day 11, pre-dose |
|
| SBP, Day 12, pre-dose |
|
| SBP, Day 13, pre-dose |
|
| SBP, Day 14, pre-dose |
|
| SBP, Day 14, 24 hours |
|
| 1 hour |
|
| 6 hour |
|
| 12 hour |
|
| 24 hour |
|
| Day 4, pre-dose |
|
| Day 5, pre-dose |
|
| Day 6, pre-dose |
|
| Day 7, pre-dose |
|
| Day 8, pre-dose |
|
| Day 9, pre-dose |
|
| Day 10, pre-dose |
|
| Day 11, pre-dose |
|
| Day 12, pre-dose |
|
| Day 13, pre-dose |
|
| Day 14, pre-dose |
|
| Day 14, 24 hours |
|
| 1 hour |
|
| 6 hour |
|
| 12 hour |
|
| 24 hour |
|
| Day 4, pre-dose |
|
| Day 5, pre-dose |
|
| Day 6, pre-dose |
|
| Day 7, pre-dose |
|
| Day 8, pre-dose |
|
| Day 9, pre-dose |
|
| Day 10, pre-dose |
|
| Day 11, pre-dose |
|
| Day 12, pre-dose |
|
| Day 13, pre-dose |
|
| Day 14, pre-dose |
|
| Day 14, 24 hours |
|
| 1 hour |
|
| 6 hour |
|
| 12 hour |
|
| 24 hour |
|
| Day 4, pre-dose |
|
| Day 5, pre-dose |
|
| Day 6, pre-dose |
|
| Day 7, pre-dose |
|
| Day 8, pre-dose |
|
| Day 9, pre-dose |
|
| Day 10, pre-dose |
|
| Day 11, pre-dose |
|
| Day 12, pre-dose |
|
| Day 13, pre-dose |
|
| Day 14, pre-dose |
|
| Day 14, 24 hours |
|
| 1 hour |
|
| Day 1,1 hour |
|
| Day 2,pre-dose |
|
| Day 2,1 hour |
|
| Day 3,pre-dose |
|
| Day 3,1 hour |
|
| Day 4,pre-dose |
|
| Day 4,1 hour |
|
| Day 5,pre-dose |
|
| Day 5,1 hour |
|
| Day 6,pre-dose |
|
| Day 6,1 hour |
|
| Day 7,pre-dose |
|
| Day 7,1 hour |
|
| Day 8,pre-dose |
|
| Day 8,1 hour |
|
| Day 9,pre-dose |
|
| Day 9,1 hour |
|
| Day 10,pre-dose |
|
| Day 10,1 hour |
|
| Day 11,pre-dose |
|
| Day 11,1 hour |
|
| Day 12,pre-dose |
|
| Day 12,1 hour |
|
| Day 13,pre-dose |
|
| Day 13,1 hour |
|
| Day 14,pre-dose |
|
| Day 14,1 hour |
|
| Abnormal - clinically significant |
|
| Alanine Amino Transferase; to high |
|
| Aspartate Amino Transferase; to high |
|
| Total Bilirubin; to high |
|
| Calcium; to high |
|
| Calcium; to low |
|
| Glucose; to high |
|
| Glucose; to low |
|
| Potassium; to high |
|
| Potassium; to low |
|
| Sodium; to high |
|
| Sodium; to low |
|
| Alkaline Phosphatase,Day 4;to high,n=3,9 |
|
|
| Alkaline Phosphatase,Day 6;to high,n=3,9 |
|
|
| Alkaline Phosphatase,Day 8;to high,n=3,9 |
|
|
| Alkaline Phosphatase,Day 10;to high,n=3,9 |
|
|
| Alkaline Phosphatase,Day 12;to high,n=3,9 |
|
|
| Alkaline Phosphatase,Day 14,pre-dose;to high,n=3,9 |
|
|
| Alkaline Phosphatase,Day 14,24 hour;to high,n=3,9 |
|
|
| Alanine Amino Transferase,Day 2;to high,n=3,9 |
|
|
| Alanine Amino Transferase,Day 4;to high,n=3,9 |
|
|
| Alanine Amino Transferase,Day 6;to high,n=3,9 |
|
|
| Alanine Amino Transferase,Day 8;to high,n=3,9 |
|
|
| Alanine Amino Transferase,Day 10;to high,n=3,9 |
|
|
| Alanine Amino Transferase,Day 12;to high,n=3,9 |
|
|
| Alanine Amino Transferase,Day 14,pre dose;to n=3,9 |
|
|
| Alanine Amino Transferase,Day 14,24 hour;to hn=3,9 |
|
|
| Aspartate Amino Transferase,Day 2;to high,n=3,8 |
|
|
| Aspartate Amino Transferase,Day 4;to high,n=3,9 |
|
|
| Aspartate Amino Transferase,Day 6;to high,n=3,9 |
|
|
| Aspartate Amino Transferase,Day 8;to high,n=3,9 |
|
|
| Aspartate Amino Transferase,Day 10;to high,n=3,9 |
|
|
| Aspartate Amino Transferase,Day 12;to high,n=3,9 |
|
|
| Aspartate Amino Transferase,Day 14,pre dose;n=2,9 |
|
|
| Aspartate Amino Transferase,Day 14,24 hour,n=3,8 |
|
|
| Total Bilirubin,Day 2,;to high,n=3,9 |
|
|
| Total Bilirubin,Day 4;to high,n=3,9 |
|
|
| Total Bilirubin,Day 6;to high,n=3,9 |
|
|
| Total Bilirubin,Day 8;to high,n=3,9 |
|
|
| Total Bilirubin,Day 10;to high,n=3,9 |
|
|
| Total Bilirubin,Day 12;to high,n=3,9 |
|
|
| Total Bilirubin,Day 14,pre dose,n=3,9 |
|
|
| Total Bilirubin,Day 14,24 hours,n=3,9 |
|
|
| Calcium,Day 2;to high,n=3,9 |
|
|
| Calcium,Day 2;to low,n=3,9 |
|
|
| Calcium,Day 4;to high,n=3,9 |
|
|
| Calcium,Day 4;to low,n=3,9 |
|
|
| Calcium,Day 6;to high,n=3,9 |
|
|
| Calcium,Day 6;to low,n=3,9 |
|
|
| Calcium,Day 8;to high,n=3,9 |
|
|
| Calcium,Day 8;to low,n=3,9 |
|
|
| Calcium,Day 10;to high,n=3,9 |
|
|
| Calcium,Day 10;to low,n=3,9 |
|
|
| Calcium,Day 12;to high,n=3,9 |
|
|
| Calcium,Day 12;to low,n=3,9 |
|
|
| Calcium,Day 14,pre dose,to high,n=3,9 |
|
|
| Calcium,Day 14,pre dose,to low,n=3,9 |
|
|
| Calcium,Day 14,24 hour,to high,n=3,9 |
|
|
| Calcium,Day 14,24 hour,to low,n=3,9 |
|
|
| Glucose,Day 2;to high,n=3,9 |
|
|
| Glucose,Day 2;to low,n=3,9 |
|
|
| Glucose,Day 4;to high,n=3,9 |
|
|
| Glucose,Day 4;to low,n=3,9 |
|
|
| Glucose,Day 6;to high,n=3,9 |
|
|
| Glucose,Day 6;to low, n=3,9 |
|
|
| Glucose,Day 8;to high,n=3,9 |
|
|
| Glucose,Day 8;to low,n=3,9 |
|
|
| Glucose,Day 10;to high,n=3,9 |
|
|
| Glucose,Day 10;to low,,n=3,9 |
|
|
| Glucose,Day 12;to high,n=3,9 |
|
|
| Glucose,Day 12;to low,n=3,9 |
|
|
| Glucose,Day 14;pre dose,to high,n=3,9 |
|
|
| Glucose,Day 14;pre dose,to low,n=3,9 |
|
|
| Glucose,Day 14;24 hours,to high,n=3,9 |
|
|
| Glucose,Day 14;24 hours,to low,n=3,9 |
|
|
| Potassium,Day 2;to high,n=3,9 |
|
|
| Potassium,Day 2;to low,n=3,9 |
|
|
| Potassium,Day 4;to high,n=3,9 |
|
|
| Potassium,Day 4,n=3,9 |
|
|
| Potassium,Day 6;to high,n=3,9 |
|
|
| Potassium,Day 6,to low,n=3,9 |
|
|
| Potassium,Day 8;to high,n=3,9 |
|
|
| Potassium,Day 8, to low,n=3,9 |
|
|
| Potassium,Day 10;to high,,n=3,9 |
|
|
| Potassium,Day 10,to low,n=3,9 |
|
|
| Potassium,Day 12;to high,,n=3,9 |
|
|
| Potassium,Day 12,to low,n=3,9 |
|
|
| Potassium,Day 14,pre dose,to high,n=3,9 |
|
|
| Potassium,Day 14,pre dose,to low,n=3,9 |
|
|
| Potassium,Day 14,24 hour ,to low,n=3,9 |
|
|
| Potassium,Day 14,24 hour,to low,n=3,9 |
|
|
| Sodium,Day 2, to high,n=3,9 |
|
|
| Sodium,Day 2, to low,n=3,9 |
|
|
| Sodium,Day 4, to high,n=3,9 |
|
|
| Sodium,Day 4, to low,n=3,9 |
|
|
| Sodium,Day 6, to high,n=3,9 |
|
|
| Sodium,Day 6, to low,n=3,9 |
|
|
| Sodium,Day 8, to high,n=3,9 |
|
|
| Sodium,Day 8, to low,n=3,9 |
|
|
| Sodium,Day 10, to high,n=3,9 |
|
|
| Sodium,Day 10, to low,n=3,9 |
|
|
| Sodium,Day 12, to high,n=3,9 |
|
|
| Sodium,Day 12, to low,n=3,9 |
|
|
| Sodium,Day 14,pre dose, to high,n=3,9 |
|
|
| Sodium,Day 14,pre dose, to low,n=3,9 |
|
|
| Sodium,Day 14,24 hour, to high,n=3,9 |
|
|
| Sodium,Day 14,24 hour, to low,n=3,9 |
|
|
|
| Hematocrit; to high,n=23,12,12,13,12,9,12 |
|
|
| Lymphocytes; to low,n=23,12,12,13,12,9,12 |
|
|
| Total Neutrophils; to low,n=23,12,12,13,12,9,12 |
|
|
| Platelet count;to high;n=23, 12, 11, 13, 11, 9, 11 |
|
|
| Platelet count; to low;n=23, 12, 11, 13, 11, 9, 11 |
|
|
| WBC count,to high,n=23, 12, 12, 13, 12, 9, 12 |
|
|
| WBC count,to low,n=23, 12, 12, 13, 12, 9, 12 |
|
|
| Hemoglobin,Day 6 |
|
| Hemoglobin,Day 8 |
|
| Hemoglobin,Day 10 |
|
| Hemoglobin,Day 12 |
|
| Hemoglobin,Day 14,pre dose |
|
| Hemoglobin,Day 14,24 hour |
|
| Hematocrit,Day 2 |
|
| Hematocrit,Day 4 |
|
| Hematocrit,Day 6 |
|
| Hematocrit,Day 8 |
|
| Hematocrit,Day 10 |
|
| Hematocrit,Day 12 |
|
| Hematocrit,Day 14,pre dose |
|
| Hematocrit,Day 14,24 hour |
|
| Lymphocytes,Day 2 |
|
| Lymphocytes,Day 4 |
|
| Lymphocytes,Day 6 |
|
| Lymphocytes,Day 8 |
|
| Lymphocytes,Day 10 |
|
| Lymphocytes,Day 12 |
|
| Lymphocytes,Day 14,pre dose |
|
| Lymphocytes,Day 14,24 hour |
|
| Total Neutrophils,Day 2 |
|
| Total Neutrophils,Day 4 |
|
| Total Neutrophils,Day 6 |
|
| Total Neutrophils,Day 8 |
|
| Total Neutrophils,Day 10 |
|
| Total Neutrophils,Day 12 |
|
| Total Neutrophils,Day 14,pre dose |
|
| Total Neutrophils,Day 14,24 hour |
|
| Platelet count,Day 2 |
|
| Platelet count,Day 4 |
|
| Platelet count,Day 6 |
|
| Platelet count,Day 8 |
|
| Platelet count,Day 10 |
|
| Platelet count,Day 12 |
|
| Platelet count,Day 14,pre dose |
|
| Platelet count,Day 14,24 hour |
|
| WBC count,Day 2 |
|
| WBC count,Day 4 |
|
| WBC count,Day 6 |
|
| WBC count,Day 8 |
|
| WBC count,Day 10 |
|
| WBC count,Day 12 |
|
| WBC count,Day 14,pre dose |
|
| WBC count,Day 14,24 hour |
|
|
| AUC(0-inf);n=0,2,5,7,6,10 |
|
|
| AUC (0-t);n=12,12,12,12,9,12 |
|
|
| Ratio |
| 0.98 |
| Standard Error of the Mean |
| 0.243 |
| 2-Sided |
| 90 |
| 0.65 |
| 1.47 |
AUC(0-t).Standard error of mean was on logged scale |
| Other |
| Ratio | 1.33 | Standard Error of the Mean | 0.161 | 2-Sided | 90 | 1.01 | 1.74 | AUC(0-t).Standard error of mean was on logged scale | Other |
| Ratio | 1.06 | Standard Error of the Mean | 0.255 | 2-Sided | 90 | 0.69 | 1.62 | AUC(0-t).Standard error of mean was on logged scale | Other |
| Ratio | 1.25 | Standard Error of the Mean | 0.161 | 2-Sided | 90 | 0.95 | 1.64 | AUC(0-t).Standard error of mean was on logged scale | Other |
|
| AUC(0-inf); Day 1; n=7 |
|
|
| AUC(0-inf);Day 14; n=7 |
|
|
| AUC (0-t); Day 1; n=9 |
|
|
| AUC (0-t); Day 14; n=9 |
|
|
| ratio |
| 0.96 |
| Standard Error of the Mean |
| 0.145 |
| 2-Sided |
| 90 |
| 0.75 |
| 1.22 |
| Other |
| ratio | 0.81 | Standard Error of the Mean | 0.106 | 2-Sided | 90 | 0.68 | 0.97 | Other |
| ratio | 0.66 | Standard Error of the Mean | 0.154 | 2-Sided | 90 | 0.51 | 0.86 | Other |
| ratio | 0.76 | Standard Error of the Mean | 0.106 | 2-Sided | 90 | 0.63 | 0.90 | Other |
| Title | Measurements |
|---|---|
|
| Day 4 |
|
| Day 5 |
|
| Day 6 |
|
| Day 7 |
|
| Day 8 |
|
| Day 9 |
|
| Day 10 |
|
| Day 11 |
|
| Day 12 |
|
| Day 13 |
|
| Day 14 |
|
|
| Day 3;n=9 |
|
|
| Day 4;n=9 |
|
|
| Day 5;n=9 |
|
|
| Day 6;n=9 |
|
|
| Day 7;n=9 |
|
|
| Day 8;n=8 |
|
|
| Day 9;n=9 |
|
|
| Day 10;n=9 |
|
|
| Day 11;n=9 |
|
|
| Day 12;n=8 |
|
|
| Day 13;n=8 |
|
|
| Day 14;n=9 |
|
|
| 24 Hr Wash 3,n=7 |
|
|