Trial Outcomes & Findings for Safety, Tolerability and Pharmacokinetics (PK) Study of GSK2269557 in Healthy Subjects (NCT NCT03189589)
NCT ID: NCT03189589
Last Updated: 2019-08-19
Results Overview
Whole blood samples of approximately 2 milliliters were collected for measurement of plasma concentrations of GSK2269557 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population which comprised of all randomized participants in the Safety Population and for whom a PK sample was obtained and analyzed.
COMPLETED
PHASE1
12 participants
Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose
2019-08-19
Participant Flow
The study was conducted at a single center in the United Kingdom from 15-June-2017 to 24-July-2017.
A total of 19 participants were screened for this study, of which 7 participants were screen failures and 12 participants were randomized to treatment. The reasons for screen failure were: did not meet inclusion/exclusion criteria (6 participants) and withdrawal by participant (1 participant).
Participant milestones
| Measure |
GSK2269557 500 mcg
Eligible participants received a single dose of GSK2269557 500 micrograms (mcg) via the ELLIPTA dry powder inhaler (DPI) on Day 1.
|
GSK2269557 750 mcg
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability and Pharmacokinetics (PK) Study of GSK2269557 in Healthy Subjects
Baseline characteristics by cohort
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.8 Years
STANDARD_DEVIATION 6.21 • n=5 Participants
|
42.7 Years
STANDARD_DEVIATION 10.98 • n=7 Participants
|
48.3 Years
STANDARD_DEVIATION 10.31 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dosePopulation: PK Population.
Whole blood samples of approximately 2 milliliters were collected for measurement of plasma concentrations of GSK2269557 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population which comprised of all randomized participants in the Safety Population and for whom a PK sample was obtained and analyzed.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Mean GSK2269557 Plasma Concentration
Pre-dose
|
0.0 Picograms per milliliter
Standard Deviation 0.00
|
0.0 Picograms per milliliter
Standard Deviation 0.00
|
|
Mean GSK2269557 Plasma Concentration
5 minutes post-dose
|
2175.5 Picograms per milliliter
Standard Deviation 843.68
|
1871.8 Picograms per milliliter
Standard Deviation 985.15
|
|
Mean GSK2269557 Plasma Concentration
30 minutes post-dose
|
480.7 Picograms per milliliter
Standard Deviation 155.28
|
530.7 Picograms per milliliter
Standard Deviation 260.82
|
|
Mean GSK2269557 Plasma Concentration
2 hours post-dose
|
322.9 Picograms per milliliter
Standard Deviation 83.85
|
414.6 Picograms per milliliter
Standard Deviation 187.63
|
|
Mean GSK2269557 Plasma Concentration
6 hours post-dose
|
259.7 Picograms per milliliter
Standard Deviation 81.60
|
424.0 Picograms per milliliter
Standard Deviation 186.51
|
|
Mean GSK2269557 Plasma Concentration
12 hours post-dose
|
210.5 Picograms per milliliter
Standard Deviation 52.94
|
319.5 Picograms per milliliter
Standard Deviation 109.94
|
|
Mean GSK2269557 Plasma Concentration
24 hours post-dose
|
171.8 Picograms per milliliter
Standard Deviation 48.71
|
248.9 Picograms per milliliter
Standard Deviation 71.92
|
|
Mean GSK2269557 Plasma Concentration
48 hours post-dose
|
114.0 Picograms per milliliter
Standard Deviation 38.31
|
145.2 Picograms per milliliter
Standard Deviation 40.54
|
|
Mean GSK2269557 Plasma Concentration
120 hours post-dose
|
36.3 Picograms per milliliter
Standard Deviation 19.30
|
40.1 Picograms per milliliter
Standard Deviation 26.37
|
PRIMARY outcome
Timeframe: Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dosePopulation: PK Population.
Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
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 GSK2269557
AUC (0 to t), n=6,6
|
14032.8 Hours*picograms per milliliter
Standard Deviation 5027.09
|
18468.7 Hours*picograms per milliliter
Standard Deviation 7007.72
|
|
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 GSK2269557
AUC (0 to 24), n=6,6
|
6000.6 Hours*picograms per milliliter
Standard Deviation 1646.07
|
8497.7 Hours*picograms per milliliter
Standard Deviation 3189.43
|
|
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 GSK2269557
AUC (0 to inf), n=4,5
|
19291.7 Hours*picograms per milliliter
Standard Deviation 3788.10
|
23340.9 Hours*picograms per milliliter
Standard Deviation 6395.14
|
PRIMARY outcome
Timeframe: Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dosePopulation: PK Population.
Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Maximum Observed Plasma Drug Concentration (Cmax) and Concentration at Trough (Ctrough) of GSK2269557
Cmax
|
2175.5 Picograms per milliliter
Standard Deviation 843.68
|
1871.8 Picograms per milliliter
Standard Deviation 985.15
|
|
Maximum Observed Plasma Drug Concentration (Cmax) and Concentration at Trough (Ctrough) of GSK2269557
Ctrough
|
171.8 Picograms per milliliter
Standard Deviation 48.71
|
248.9 Picograms per milliliter
Standard Deviation 71.92
|
PRIMARY outcome
Timeframe: Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dosePopulation: PK Population.
Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Time to Maximum Observed Plasma Drug Concentration (Tmax) and Terminal Half-life (t1/2)
Tmax, n=6,6
|
0.083 Hours
Interval 0.08 to 0.1
|
0.083 Hours
Interval 0.07 to 0.083
|
|
Time to Maximum Observed Plasma Drug Concentration (Tmax) and Terminal Half-life (t1/2)
t1/2, n=4,5
|
42.7 Hours
Interval 42.0 to 48.0
|
38.2 Hours
Interval 31.0 to 49.0
|
SECONDARY outcome
Timeframe: Up to Day 2Population: Safety Population
Vital signs included blood pressure (systolic and diastolic blood pressure) and heart rate measurements and were assessed with the participant in a semi-supine position after 5 minutes rest. The potential clinical concern range values for vital signs were: systolic blood pressure (lower \<85 millimeters of mercury and higher \>160 millimeters of mercury), diastolic blood pressure (lower \<45 millimeters of mercury and higher \>100 millimeters of mercury) and heart rate (lower \<40 beats per minute and higher \>110 beats per minute). Number of participants with vital signs of potential clinical importance are presented. Safety Population comprised of all randomized participants who received at least one dose of study treatment.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Number of Participants With Vital Signs of Potential Clinical Importance
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 2Population: Safety Population.
Twelve-lead ECG was obtained using an ECG machine which automatically measured PR, QRS, QT and corrected QT (QTc) intervals. ECG parameters and their potential clinical importance range values were: absolute QTc interval (lower \>450 milliseconds \[msec\]), absolute PR interval (lower \<110 msec and upper \>220 msec), absolute QRS interval (lower \<75 msec and upper \>110 msec). Number of participants with electrocardiogram (ECG) values of potential clinical importance are presented.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline and Day 1Population: Safety Population.
The maximal amount of air forcefully exhaled in 1 second (FEV1) and forced vital capacity (FVC) was measured using a spirometer. Baseline was latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline values from post-dose visit values. Mean change from Baseline in FVC and FEV1 is presented.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Change From Baseline in Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1)
FEV1
|
0.027 Liters (L)
Standard Deviation 0.0554
|
-0.040 Liters (L)
Standard Deviation 0.2060
|
|
Change From Baseline in Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1)
FVC
|
0.177 Liters (L)
Standard Deviation 0.0836
|
0.065 Liters (L)
Standard Deviation 0.2780
|
SECONDARY outcome
Timeframe: Up to Day 2Population: Safety Population.
Hematology parameters and their potential clinical concern values were: Hematocrit (high flag: \>0.54 and change from Baseline: decrease of 0.075), hemoglobin (high flag: \>180 grams per Liter and change from Baseline: decrease of 25 grams per Liter), lymphocytes (low flag: \<0.8\*10\^9 cells per Liter), neutrophil count (low flag: \<1.5\*10\^9 cells per Liter), platelet count (low flag: \<100\*10\^9 cells per Liter and high flag: \>550\*10\^9 cells per Liter) and white blood cell count (low flag: \<3\*10\^9 cells per Liter and high flag: \>20\*10\^9 cells per Liter). Number of participants with hematology abnormalities of potential clinical importance are presented.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Number of Participants With Hematology Abnormalities of Potential Clinical Importance
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 2Population: Safety Population.
Clinical chemistry parameters and their potential clinical concern range values were: calcium (low flag \<2 millimoles/Liter \[mmol/L\] and high flag \>2.75 mmol/L), creatinine (high flag \>44.2 micromoles/Liter increase in change from Baseline), glucose (fasting) (\<3 mmol/L and \>9 mmol/L), potassium (low flag \<3 mmol/L and high flag \>5.5 mmol/L above ULN), sodium (low flag \<130 mmol/L and high flag \>150 mmol/L). Number of participants with clinical chemistry abnormalities of potential clinical importance are presented.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 12 days post-dosePopulation: Safety Population.
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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. 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.
Outcome measures
| Measure |
GSK2269557 500 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 Participants
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
AE
|
3 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
SAE
|
0 Participants
|
0 Participants
|
Adverse Events
GSK2269557 500 mcg
GSK2269557 750 mcg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
GSK2269557 500 mcg
n=6 participants at risk
Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1.
|
GSK2269557 750 mcg
n=6 participants at risk
Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1.
|
|---|---|---|
|
General disorders
Fatigue
|
0.00%
0/6 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
33.3%
2/6 • Number of events 2 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
|
General disorders
Catheter site inflammation
|
0.00%
0/6 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
16.7%
1/6 • Number of events 1 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
16.7%
1/6 • Number of events 1 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Somnolence
|
16.7%
1/6 • Number of events 1 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
0.00%
0/6 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Constipation
|
16.7%
1/6 • Number of events 1 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
0.00%
0/6 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Limb injury
|
16.7%
1/6 • Number of events 1 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
0.00%
0/6 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
16.7%
1/6 • Number of events 1 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
0.00%
0/6 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
16.7%
1/6 • Number of events 1 • Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
|
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