Trial Outcomes & Findings for Absorption & Elimination of Radiolabelled GSK2269557 (NCT NCT03315559)
NCT ID: NCT03315559
Last Updated: 2020-03-13
Results Overview
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic (PK) Population comprised of participants in the APE Population who received at least one dose of study treatment and for whom a PK sample was obtained and analyzed. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
6 participants
Primary outcome timeframe
Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion
Results posted on
2020-03-13
Participant Flow
The study was conducted at a single center in the United Kingdom from 14-November-2017 to 22-December-2017.
A total of 7 participants were screened, of which 1 participant was a reserve participant and was not used. The remaining 6 participants were enrolled.
Participant milestones
| Measure |
All Study Participants
Participants received intravenous (IV) infusion of \[14C\] radiolabeled GSK2269557 along with a single dose of 10 micrograms (µg) administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557 in Treatment Period 1. There was a washout of at least 14 days. Participants received \[14C\]-GSK2269557 with a single dose of 800 µg, administered as an oral solution in Treatment Period 2.
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|---|---|
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Treatment Period 1 (8 Days)
STARTED
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6
|
|
Treatment Period 1 (8 Days)
COMPLETED
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6
|
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Treatment Period 1 (8 Days)
NOT COMPLETED
|
0
|
|
Washout Period (14 Days)
STARTED
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6
|
|
Washout Period (14 Days)
COMPLETED
|
6
|
|
Washout Period (14 Days)
NOT COMPLETED
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0
|
|
Treatment Period 2 (15 Days)
STARTED
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6
|
|
Treatment Period 2 (15 Days)
COMPLETED
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6
|
|
Treatment Period 2 (15 Days)
NOT COMPLETED
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0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Absorption & Elimination of Radiolabelled GSK2269557
Baseline characteristics by cohort
| Measure |
All Study Participants
n=6 Participants
Participants received intravenous (IV) infusion of \[14C\] radiolabeled GSK2269557 along with a single dose of 10 micrograms (µg) administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557 in Treatment Period 1. There was a washout of at least 14 days. Participants received \[14C\]-GSK2269557 with a single dose of 800 µg, administered as an oral solution in Treatment Period 2.
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|---|---|
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Age, Continuous
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43.3 Years
STANDARD_DEVIATION 10.03 • n=5 Participants
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|
Sex: Female, Male
Female
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0 Participants
n=5 Participants
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|
Sex: Female, Male
Male
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6 Participants
n=5 Participants
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|
Race/Ethnicity, Customized
African American/African Heritage
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2 Count of participants
n=5 Participants
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|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
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4 Count of participants
n=5 Participants
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PRIMARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic (PK) Population comprised of participants in the APE Population who received at least one dose of study treatment and for whom a PK sample was obtained and analyzed. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
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|---|---|---|
|
Area Under Concentration-time Curve (AUC) From Time 0 (Pre-dose) to Infinite Time (0 to Inf) and AUC From Time 0 (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1
AUC (0 to inf), n=3
|
812.8550 Hour*picogram Equivalent per millilitre
Geometric Coefficient of Variation 8.17885
|
—
|
|
Area Under Concentration-time Curve (AUC) From Time 0 (Pre-dose) to Infinite Time (0 to Inf) and AUC From Time 0 (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1
AUC (0 to t), n=6
|
770.3316 Hour*picogram Equivalent per millilitre
Geometric Coefficient of Variation 17.70272
|
—
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PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dosePopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. NA indicates that data is not available as single participant was analyzed.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
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|---|---|---|
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AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (0 to Inf) and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2
AUC (0 to inf), n=1
|
34749.40 Hour*picogram Equivalent per millilitre
Geometric Coefficient of Variation NA
NA indicates that data is not available as single participant was analyzed
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—
|
|
AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (0 to Inf) and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2
AUC (0 to t), n=6
|
31730.13 Hour*picogram Equivalent per millilitre
Geometric Coefficient of Variation 35.715
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
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|---|---|---|
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Maximum Observed Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1
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204.4057 Picogram Equivalent per milliliter
Geometric Coefficient of Variation 52.32698
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—
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PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dosePopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
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|---|---|---|
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Cmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2
|
703.5192 Picogram Equivalent per milliliter
Geometric Coefficient of Variation 24.43331
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
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|---|---|---|
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Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1
|
0.2333 Hours
Interval 0.2333 to 0.2333
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—
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dosePopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Tmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2
|
7.0000 Hours
Interval 2.0 to 8.017
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—
|
PRIMARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population. Only those participants available at the indicated time points were analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=3 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
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|---|---|---|
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Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1
|
56.9152 Hours
Geometric Coefficient of Variation 7.69827
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—
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dosePopulation: PK Population. Only those participants available at the indicated time points were analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis. NA indicates that data is not available as single participant was analyzed.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=1 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
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|---|---|---|
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Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2
|
39.6279 Hours
Geometric Coefficient of Variation NA
NA indicates that data is not available as single participant was analyzed
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—
|
PRIMARY outcome
Timeframe: Up to 168 hoursPopulation: PK Population.
Urine samples and fecal samples were collected to measure total radiolabeled drug-related material excreted in urine and feces respectively.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
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|---|---|---|
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Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Urine, 48 to 72 hour
|
9.3483 Percentage of dose excreted
Standard Deviation 2.26387
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—
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Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Feces, 0 to 24 hour
|
0.3961 Percentage of dose excreted
Standard Deviation 0.83271
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—
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|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Feces, 24 to 48 hour
|
2.1998 Percentage of dose excreted
Standard Deviation 3.77158
|
—
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Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Feces, 48 to 72 hour
|
18.1265 Percentage of dose excreted
Standard Deviation 12.97670
|
—
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|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Feces, 72 to 96 hour
|
28.0481 Percentage of dose excreted
Standard Deviation 18.22334
|
—
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|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Feces, 96 to 120 hour
|
33.7465 Percentage of dose excreted
Standard Deviation 19.02044
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—
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Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Feces, 120 to 144 hour
|
45.2398 Percentage of dose excreted
Standard Deviation 14.63248
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—
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Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Feces, 144 to 168 hour
|
51.6981 Percentage of dose excreted
Standard Deviation 15.46780
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—
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Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Urine, 0 to 6 hour
|
2.1567 Percentage of dose excreted
Standard Deviation 0.83754
|
—
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Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Urine, 6 to 24 hour
|
5.1183 Percentage of dose excreted
Standard Deviation 1.53825
|
—
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|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Urine, 24 to 48 hour
|
7.6850 Percentage of dose excreted
Standard Deviation 2.04159
|
—
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|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Urine, 72 to 96 hour
|
10.7150 Percentage of dose excreted
Standard Deviation 2.46640
|
—
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|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Urine, 96 to 120 hour
|
11.6400 Percentage of dose excreted
Standard Deviation 2.52790
|
—
|
|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Urine, 120 to 144 hour
|
12.3607 Percentage of dose excreted
Standard Deviation 2.56693
|
—
|
|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Urine, 144 to 168 hour
|
12.9205 Percentage of dose excreted
Standard Deviation 2.57056
|
—
|
|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Total (Urine+Feces), 0 to 24 hour
|
5.5145 Percentage of dose excreted
Standard Deviation 1.30554
|
—
|
|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Total (Urine+Feces), 24 to 48 hour
|
9.8848 Percentage of dose excreted
Standard Deviation 3.03062
|
—
|
|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Total (Urine+Feces), 48 to 72 hour
|
27.4748 Percentage of dose excreted
Standard Deviation 13.02973
|
—
|
|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Total (Urine+Feces), 72 to 96 hour
|
38.7631 Percentage of dose excreted
Standard Deviation 18.40877
|
—
|
|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Total (Urine+Feces), 96 to 120 hour
|
45.3865 Percentage of dose excreted
Standard Deviation 19.01459
|
—
|
|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Total (Urine+Feces), 120 to 144 hour
|
57.6005 Percentage of dose excreted
Standard Deviation 14.46954
|
—
|
|
Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1
Fe Total (Urine+Feces), 144 to 168 hour
|
64.6186 Percentage of dose excreted
Standard Deviation 15.25339
|
—
|
PRIMARY outcome
Timeframe: Up to 336 hoursPopulation: PK Population.
Urine samples and fecal samples were collected to measure total radiolabeled drug-related material excreted in urine and feces respectively. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 0 to 24 hour; n=6
|
3.81330 Percentage of dose excreted
Standard Deviation 7.16484
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 168 to 192 hour; n=6
|
5.1383 Percentage of dose excreted
Standard Deviation 1.16426
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 24 to 48 hour; n=6
|
14.6367 Percentage of dose excreted
Standard Deviation 21.64607
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 48 to 72 hour; n=6
|
40.9583 Percentage of dose excreted
Standard Deviation 28.48392
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 72 to 96 hour; n=6
|
48.8217 Percentage of dose excreted
Standard Deviation 29.60581
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 96 to 120 hour; n=6
|
60.7617 Percentage of dose excreted
Standard Deviation 18.24192
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 120 to 144 hour; n=6
|
64.1667 Percentage of dose excreted
Standard Deviation 19.65337
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 144 to 168 hour; n=6
|
72.4217 Percentage of dose excreted
Standard Deviation 6.66365
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 168 to 192 hour; n=6
|
75.1117 Percentage of dose excreted
Standard Deviation 5.29605
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 192 to 216 hour; n=6
|
77.0917 Percentage of dose excreted
Standard Deviation 4.59090
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 216 to 240 hour; n=6
|
77.5933 Percentage of dose excreted
Standard Deviation 4.12513
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 240 to 264 hour; n=6
|
78.7917 Percentage of dose excreted
Standard Deviation 3.82906
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 264 to 288 hour; n=5
|
78.6820 Percentage of dose excreted
Standard Deviation 4.07492
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 288 to 312 hour; n=3
|
80.9500 Percentage of dose excreted
Standard Deviation 3.78747
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Feces, 312 to 336 hour; n=3
|
81.1500 Percentage of dose excreted
Standard Deviation 3.57979
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 0 to 6 hour; n=6
|
0.3867 Percentage of dose excreted
Standard Deviation 0.09668
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 6 to 24 hour; n=6
|
1.7017 Percentage of dose excreted
Standard Deviation 0.42995
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 24 to 48 hour; n=6
|
2.7183 Percentage of dose excreted
Standard Deviation 0.73249
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 48 to 72 hour; n=6
|
3.4250 Percentage of dose excreted
Standard Deviation 0.89063
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 72 to 96 hour; n=6
|
3.9600 Percentage of dose excreted
Standard Deviation 0.97980
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 96 to 120 hour; n=6
|
4.3617 Percentage of dose excreted
Standard Deviation 1.02918
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 120 to 144 hour; n=6
|
4.6717 Percentage of dose excreted
Standard Deviation 1.09549
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 144 to 168 hour; n=6
|
4.9217 Percentage of dose excreted
Standard Deviation 1.12583
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 192 to 216 hour; n=6
|
5.2950 Percentage of dose excreted
Standard Deviation 1.16156
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 216 to 240 hour; n=6
|
5.4700 Percentage of dose excreted
Standard Deviation 1.20854
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 240 to 264 hour; n=6
|
5.5617 Percentage of dose excreted
Standard Deviation 1.24856
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 264 to 288 hour; n=5
|
5.4760 Percentage of dose excreted
Standard Deviation 1.35858
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 288 to 312 hour; n=3
|
5.7800 Percentage of dose excreted
Standard Deviation 1.43293
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Urine, 312 to 336 hour; n=3
|
5.8133 Percentage of dose excreted
Standard Deviation 1.45590
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 0 to 24 hour; n=6
|
5.5150 Percentage of dose excreted
Standard Deviation 7.01205
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 24 to 48 hour; n=6
|
17.3550 Percentage of dose excreted
Standard Deviation 21.303
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 48 to 72 hour; n=6
|
44.3833 Percentage of dose excreted
Standard Deviation 28.28365
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 72 to 96 hour; n=6
|
52.7817 Percentage of dose excreted
Standard Deviation 29.36619
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 96 to 120 hour; n=6
|
65.1233 Percentage of dose excreted
Standard Deviation 17.8525
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 120 to 144 hour; n=6
|
68.8383 Percentage of dose excreted
Standard Deviation 19.24589
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 144 to 168 hour; n=6
|
77.3433 Percentage of dose excreted
Standard Deviation 6.27302
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 168 to 192 hour; n=6
|
80.2500 Percentage of dose excreted
Standard Deviation 4.74848
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 192 to 216 hour; n=6
|
82.3867 Percentage of dose excreted
Standard Deviation 3.98209
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 216 to 240 hour; n=6
|
83.0633 Percentage of dose excreted
Standard Deviation 3.3933
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 240 to 264 hour; n=6
|
84.3533 Percentage of dose excreted
Standard Deviation 3.17528
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 264 to 288 hour; n=5
|
84.158 Percentage of dose excreted
Standard Deviation 3.25412
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 288 to 312 hour; n=3
|
86.7300 Percentage of dose excreted
Standard Deviation 2.44851
|
—
|
|
Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2
Fe Total (Urine+Feces), 312 to 336 hour; n=3
|
86.9633 Percentage of dose excreted
Standard Deviation 2.16207
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
GSK2269557: AUC (0 to inf), n=6
|
33374.56 Hour*picogram per milliliter
Geometric Coefficient of Variation 33.190
|
—
|
|
AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
GSK2269557: AUC (0 to t), n=6
|
28425.82 Hour*picogram per milliliter
Geometric Coefficient of Variation 34.474
|
—
|
|
AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
[14C]-GSK2269557: AUC (0 to inf), n=4
|
750.5798 Hour*picogram per milliliter
Geometric Coefficient of Variation 48.27760
|
—
|
|
AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
[14C]-GSK2269557: AUC (0 to t), n=6
|
546.4731 Hour*picogram per milliliter
Geometric Coefficient of Variation 45.31868
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dosePopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
AUC (0 to Inf) and AUC (0 to t) of [14C]-GSK2269557 in Plasma for Treatment Period 2
AUC (0 to inf), n=4
|
25107.96 Hour*picogram per milliliter
Geometric Coefficient of Variation 46.310
|
—
|
|
AUC (0 to Inf) and AUC (0 to t) of [14C]-GSK2269557 in Plasma for Treatment Period 2
AUC (0 to t), n=6
|
16913.06 Hour*picogram per milliliter
Geometric Coefficient of Variation 53.841
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Cmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
GSK2269557
|
5258.98 Picograms per milliliter
Geometric Coefficient of Variation 62.819
|
—
|
|
Cmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
[14C]-GSK2269557
|
205.6264 Picograms per milliliter
Geometric Coefficient of Variation 57.91419
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dosePopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Cmax of [14C]-GSK2269557 in Plasma for Treatment Period 2
|
398.8822 Picograms per milliliter
Geometric Coefficient of Variation 27.81929
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Tmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
GSK2269557
|
0.0333 Hours
Interval 0.017 to 0.05
|
—
|
|
Tmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
[14C]-GSK2269557
|
0.2333 Hours
Interval 0.2333 to 0.2333
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dosePopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Tmax of [14C]-GSK2269557 in Plasma for Treatment Period 2
|
6.0000 Hours
Interval 2.0 to 8.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. Only those participants available at the indicated time points were analyzed represented by n=X in the category titles.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
t1/2 of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
GSK2269557
|
58.4408 Hours
Geometric Coefficient of Variation 16.84150
|
—
|
|
t1/2 of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1
[14C]-GSK2269557
|
54.7223 Hours
Geometric Coefficient of Variation 35.98970
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dosePopulation: PK Population. Only those participants available at the indicated time points were analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=4 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
t1/2 of [14C]-GSK2269557 in Plasma for Treatment Period 2
|
50.8028 Hours
Geometric Coefficient of Variation 40.16665
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=4 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Volume of Distribution of Parent [14C]-GSK2269557 After IV Dose Only in Plasma
Vss
|
727.7102 Liters
Geometric Coefficient of Variation 11.24581
|
—
|
|
Volume of Distribution of Parent [14C]-GSK2269557 After IV Dose Only in Plasma
Vz
|
851.4423 Liters
Geometric Coefficient of Variation 13.98220
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population. Only those participants available at the indicated time points were analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature \[14C\]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=4 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Clearance of Parent [14C]-GSK2269557 After IV Dose Only in Plasma
|
10.7849 Liters per hour
Geometric Coefficient of Variation 46.70161
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusionPopulation: PK Population.
Absolute bioavailability (F) was estimated for the inhaled doses for each participant and is reported. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Inhaled Absolute Bioavailability (F) for Treatment Period 1
Inhaled F (0 to inf); n=4
|
0.3807 Fraction of drug
Geometric Coefficient of Variation 19.65374
|
—
|
|
Inhaled Absolute Bioavailability (F) for Treatment Period 1
Inhaled F (0 to t); n=6
|
0.4213 Fraction of drug
Geometric Coefficient of Variation 21.84410
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dosePopulation: PK Population.
Absolute bioavailability (F) was estimated for the oral doses for each participant and is reported. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Oral Absolute Bioavailability (F) for Treatment Period 2
Oral F (0 to inf); n=4
|
0.3515 Fraction of drug
Geometric Coefficient of Variation 3.35095
|
—
|
|
Oral Absolute Bioavailability (F) for Treatment Period 2
Oral F (0 to t); n=6
|
0.3261 Fraction of drug
Geometric Coefficient of Variation 12.77892
|
—
|
SECONDARY outcome
Timeframe: Up to 11 weeksPopulation: Safety Population.
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product (MP), whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
n=6 Participants
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
AE
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
SAE
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 11 weeksPopulation: Safety Population.
Hematology parameters included basophils, eosinophils, erythrocytes, monocytes, hematocrit, hemoglobin, lymphocytes, neutrophil count, platelet count and white blood cells. Number of participants with hematology parameters of potential clinical concern are presented.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
n=6 Participants
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Number of Participants With Hematology Parameters of Potential Clinical Concern
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 11 weeksPopulation: Safety Population.
Clinical chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, chloride, cholesterol, gamma glutamyl transferase, globulin, protein, triglycerides, urate, albumin, calcium, creatinine, glucose, phosphorous, potassium, urea and sodium. Number of participants with clinical chemistry parameters of potential clinical concern are presented.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
n=6 Participants
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 168 hoursPopulation: Safety Population.
Urine samples were collected to detect the presence of bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Urinalysis also included measurement of specific gravity and pH. Number of participants with clinically significant urinalysis findings are presented.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
n=6 Participants
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Number of Participants With Clinically Significant Urinalysis Findings
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 11 weeksPopulation: Safety Population.
Twelve-lead electrocardiogram was measured in a supine or semi-supine position after 5 minutes rest. Number of participants with electrocardiogram findings of clinical significance are presented.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
n=6 Participants
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Number of Participants With Electrocardiogram Findings of Clinical Significance
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 11 weeksPopulation: Safety Population
Vital signs were measured in a supine or semi-supine position after 5 minutes rest and included temperature, systolic and diastolic blood pressure and pulse and respiratory rate. Number of participants with vital signs of potential clinical concern are reported.
Outcome measures
| Measure |
Nemi IH + 14C-Nemi IV
n=6 Participants
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
n=6 Participants
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg, administered as an oral solution.
|
|---|---|---|
|
Number of Participants With Vital Signs of Potential Clinical Concern
High respiratory rate
|
1 Participants
|
0 Participants
|
|
Number of Participants With Vital Signs of Potential Clinical Concern
Low temperature
|
1 Participants
|
0 Participants
|
Adverse Events
Nemi IH + 14C-Nemi IV
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
14C-Nemi Oral
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Nemi IH + 14C-Nemi IV
n=6 participants at risk
Participants received IV infusion of \[14C\] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557.
|
14C-Nemi Oral
n=6 participants at risk
Participants received solution of \[14C\] radiolabelled GSK2269557 as a single dose of 800 µg orally
|
|---|---|---|
|
General disorders
Malaise
|
0.00%
0/6 • Serious and non serious adverse events were evaluated up to 11 weeks
Safety Population was analyzed to collect serious adverse events (SAE) and non-serious adverse events (nSAE).
|
16.7%
1/6 • Number of events 1 • Serious and non serious adverse events were evaluated up to 11 weeks
Safety Population was analyzed to collect serious adverse events (SAE) and non-serious adverse events (nSAE).
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • Serious and non serious adverse events were evaluated up to 11 weeks
Safety Population was analyzed to collect serious adverse events (SAE) and non-serious adverse events (nSAE).
|
16.7%
1/6 • Number of events 1 • Serious and non serious adverse events were evaluated up to 11 weeks
Safety Population was analyzed to collect serious adverse events (SAE) and non-serious adverse events (nSAE).
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER