Trial Outcomes & Findings for A Study to Assess the Effectiveness and Side Effects of GSK2798745 in Participants With Chronic Cough (NCT NCT03372603)
NCT ID: NCT03372603
Last Updated: 2019-10-02
Results Overview
Coughs were monitored using the VitaloJAK cough monitor. The total cough counts during day-time (10 hours) was calculated from the time of the monitor being attached i.e. immediately after dosing on Day 7 to 10 hours past the time of monitoring. Total cough counts were log-transformed prior to analysis. A non-informative prior was used. Analysis was performed using a Bayesian mixed model adjusting for subject-level and period-adjusted baselines, treatment and period. Subject-level baseline is defined as the mean of the two period-specific baselines. Period-adjusted baseline is defined as the difference between the period-specific baseline and subject-level baseline for each period. Posterior median and 95% credible interval is reported. All Subjects Population included all randomized participants who took at least 1 dose of study treatment. Participants were analyzed according to the treatment they actually received.
TERMINATED
PHASE1/PHASE2
17 participants
Up to 10 hours post-dose on Day 7 of each treatment period
2019-10-02
Participant Flow
Study was conducted at 4 centers in the United Kingdom. Participants who met eligibility criteria entered a 2-period crossover study. Participants were randomized to either placebo or GSK2798745 in each Treatment Period (each 7 days, with a 14-21 day washout). Total duration of participation was 10.5 weeks. Study terminated on grounds of futility
A total of 34 participants were screened of which 17 failed screening and 17 participants were included in the study.
Participant milestones
| Measure |
Placebo/GSK2798745
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745/Placebo
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Treatment Period 1 (Up to 7 Days)
STARTED
|
9
|
8
|
|
Treatment Period 1 (Up to 7 Days)
COMPLETED
|
9
|
8
|
|
Treatment Period 1 (Up to 7 Days)
NOT COMPLETED
|
0
|
0
|
|
Wash-out Period (14-21 Days)
STARTED
|
9
|
8
|
|
Wash-out Period (14-21 Days)
COMPLETED
|
8
|
8
|
|
Wash-out Period (14-21 Days)
NOT COMPLETED
|
1
|
0
|
|
Treatment Period 2 (Up to 7 Days)
STARTED
|
8
|
8
|
|
Treatment Period 2 (Up to 7 Days)
COMPLETED
|
7
|
8
|
|
Treatment Period 2 (Up to 7 Days)
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Placebo/GSK2798745
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745/Placebo
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Wash-out Period (14-21 Days)
Sponsor terminated study treatment
|
1
|
0
|
|
Treatment Period 2 (Up to 7 Days)
Study closed/Terminated
|
1
|
0
|
Baseline Characteristics
A Study to Assess the Effectiveness and Side Effects of GSK2798745 in Participants With Chronic Cough
Baseline characteristics by cohort
| Measure |
All Study Participants
n=17 Participants
All participants who were randomized to either of the two treatment sequences Placebo/GSK2798745 and GSK2798745/Placebo and received GSK2798745 and placebo in either Treatment period 1 or 2 were included. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|
|
Age, Continuous
|
61.0 Years
STANDARD_DEVIATION 9.85 • n=39 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Asian-Japanese/East Asian (EA)/South EA Heritage
|
1 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
White
|
16 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Up to 10 hours post-dose on Day 7 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Coughs were monitored using the VitaloJAK cough monitor. The total cough counts during day-time (10 hours) was calculated from the time of the monitor being attached i.e. immediately after dosing on Day 7 to 10 hours past the time of monitoring. Total cough counts were log-transformed prior to analysis. A non-informative prior was used. Analysis was performed using a Bayesian mixed model adjusting for subject-level and period-adjusted baselines, treatment and period. Subject-level baseline is defined as the mean of the two period-specific baselines. Period-adjusted baseline is defined as the difference between the period-specific baseline and subject-level baseline for each period. Posterior median and 95% credible interval is reported. All Subjects Population included all randomized participants who took at least 1 dose of study treatment. Participants were analyzed according to the treatment they actually received.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Total Cough Counts During Day Time Hours Following 7-days of Dosing
|
180.570 Cough counts
Interval 137.852 to 235.446
|
241.105 Cough counts
Interval 181.383 to 320.6
|
SECONDARY outcome
Timeframe: Up to 45 daysPopulation: All Subjects Population.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=16 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any AE
|
9 Participants
|
11 Participants
|
|
Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any SAE
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of clinical chemistry parameters including ALP, ALT, AST and CK. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=14 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Amino Transferase (AST) and Creatinine Kinase (CK)
ALP
|
1.8 International units per liter
Standard Deviation 9.28
|
-3.1 International units per liter
Standard Deviation 6.75
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Amino Transferase (AST) and Creatinine Kinase (CK)
ALT
|
0.2 International units per liter
Standard Deviation 2.31
|
-0.2 International units per liter
Standard Deviation 5.32
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Amino Transferase (AST) and Creatinine Kinase (CK)
AST
|
-0.6 International units per liter
Standard Deviation 3.69
|
-0.5 International units per liter
Standard Deviation 2.65
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Amino Transferase (AST) and Creatinine Kinase (CK)
CK
|
-3.0 International units per liter
Standard Deviation 21.71
|
-12.1 International units per liter
Standard Deviation 52.12
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 for each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, total bilirubin and creatinine. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=14 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Clinical Chemistry Parameter: Direct Bilirubin, Total Bilirubin and Creatinine
Direct bilirubin
|
0.1 Micromoles per liter
Standard Deviation 1.11
|
0.0 Micromoles per liter
Standard Deviation 0.78
|
|
Change From Baseline Values for Clinical Chemistry Parameter: Direct Bilirubin, Total Bilirubin and Creatinine
Total bilirubin
|
-0.4 Micromoles per liter
Standard Deviation 3.41
|
-0.4 Micromoles per liter
Standard Deviation 3.25
|
|
Change From Baseline Values for Clinical Chemistry Parameter: Direct Bilirubin, Total Bilirubin and Creatinine
Creatinine
|
0.31 Micromoles per liter
Standard Deviation 6.458
|
1.70 Micromoles per liter
Standard Deviation 4.031
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of clinical chemistry parameters including calcium, glucose, potassium, sodium and urea/blood urea nitrogen (BUN). Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=14 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea
Calcium
|
0.011 Millimoles per liter
Standard Deviation 0.0588
|
0.019 Millimoles per liter
Standard Deviation 0.0782
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea
Glucose
|
-0.22 Millimoles per liter
Standard Deviation 1.234
|
-0.06 Millimoles per liter
Standard Deviation 0.956
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea
Potassium
|
0.09 Millimoles per liter
Standard Deviation 0.299
|
0.09 Millimoles per liter
Standard Deviation 0.270
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea
Sodium
|
0.2 Millimoles per liter
Standard Deviation 1.44
|
-0.1 Millimoles per liter
Standard Deviation 1.46
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea
Urea
|
0.18 Millimoles per liter
Standard Deviation 0.683
|
-0.36 Millimoles per liter
Standard Deviation 0.908
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of clinical chemistry parameter total protein. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=14 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Clinical Chemistry Parameter: Total Protein
|
1.2 Grams per liter
Standard Deviation 2.65
|
0.9 Grams per liter
Standard Deviation 2.53
|
SECONDARY outcome
Timeframe: Up to 45 daysPopulation: All Subjects Population.
Cardiac troponin values was measured in participants.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=16 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Number of Participants With Abnormal Values of Cardiac Troponin
|
NA Participants
Not applicable (NA) indicates Troponin I values were recorded as less than lower limit of quantification (\<0.02) at all time points.
|
NA Participants
NA indicates Troponin I values were recorded as less than lower limit of quantification (\<0.02) at all time points.
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and WBC count. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
Basophils
|
0.005 Giga units per liter
Standard Deviation 0.0250
|
-0.005 Giga units per liter
Standard Deviation 0.0316
|
|
Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
Eosinophils
|
-0.005 Giga units per liter
Standard Deviation 0.0400
|
-0.007 Giga units per liter
Standard Deviation 0.0758
|
|
Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
Lymphocytes
|
0.019 Giga units per liter
Standard Deviation 0.3065
|
-0.002 Giga units per liter
Standard Deviation 0.2608
|
|
Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
Monocytes
|
-0.012 Giga units per liter
Standard Deviation 0.1110
|
0.027 Giga units per liter
Standard Deviation 0.1012
|
|
Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
Total neutrophils
|
0.186 Giga units per liter
Standard Deviation 0.5817
|
0.064 Giga units per liter
Standard Deviation 1.0102
|
|
Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
Platelet count
|
6.8 Giga units per liter
Standard Deviation 13.57
|
6.9 Giga units per liter
Standard Deviation 19.76
|
|
Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
WBC count
|
0.20 Giga units per liter
Standard Deviation 0.614
|
0.09 Giga units per liter
Standard Deviation 1.276
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 for each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Hemoglobin
|
0.5 Grams per liter
Standard Deviation 2.29
|
0.5 Grams per liter
Standard Deviation 3.52
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Hematocrit
|
0.0020 Percentage of red blood cells in blood
Standard Deviation 0.01009
|
0.0029 Percentage of red blood cells in blood
Standard Deviation 0.00979
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 for each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of hematology parameter: MCH. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
|
-0.07 Picograms
Standard Deviation 0.377
|
-0.09 Picograms
Standard Deviation 0.442
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of hematology parameter: MCV. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV)
|
-0.1 Femtoliters
Standard Deviation 2.01
|
-0.1 Femtoliters
Standard Deviation 1.53
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 for each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of hematology parameter: RBC count. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count
|
0.04 Tera units per liter
Standard Deviation 0.112
|
0.03 Tera units per liter
Standard Deviation 0.103
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 8 for each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected for the analysis of hematology parameter: reticulocytes. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Reticulocytes
|
-0.0002 Percentage of reticulocytes in blood
Standard Deviation 0.00300
|
-0.0002 Percentage of reticulocytes in blood
Standard Deviation 0.00260
|
SECONDARY outcome
Timeframe: Up to Day 8Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Urine samples were collected for analysis of urinalysis data by dipstick method. Number of participants with abnormal urinalysis data has been presented. Abnormality was defined as value of potential clinical importance (PCI). PCI was flagged when a result changed from negative on Day 1 (pre-dose) to positive on Day 8.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Number of Participants With Abnormal Urinalysis Data
|
4 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline (pre-dose on Day 1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Blood pressure was measured at indicated time points in supine position after 5 minutes rest for the participant. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP
|
-0.2 Millimeters of mercury
Standard Deviation 8.59
|
-0.5 Millimeters of mercury
Standard Deviation 13.07
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP
|
1.6 Millimeters of mercury
Standard Deviation 12.65
|
0.9 Millimeters of mercury
Standard Deviation 20.10
|
SECONDARY outcome
Timeframe: Baseline (pre-dose on Day 1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Temperature was measured at indicated time points in supine position after 5 minutes rest for the participant. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline in Temperature
|
0.02 Degrees Celsius
Standard Deviation 0.635
|
-0.05 Degrees Celsius
Standard Deviation 0.331
|
SECONDARY outcome
Timeframe: Baseline (pre-dose on Day 1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed.
Heart rate was measured at indicated time points in supine position after 5 minutes rest for the participant. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=15 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Change From Baseline in Heart Rate
|
0.6 Beats per minute
Standard Deviation 8.65
|
-1.3 Beats per minute
Standard Deviation 12.09
|
SECONDARY outcome
Timeframe: Baseline (pre-dose on Day 1) and Day 8 of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category title).
Twelve-lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with abnormal-clinically significant and abnormal-not clinically significant values has been presented.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=16 Participants
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 1 pre-dose, not clinically significant,n=17,16
|
2 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 1 pre-dose, clinically significant, n=17,16
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 8, not clinically significant, n=17,15
|
2 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 8, clinically significant, n=17,15
|
0 Participants
|
1 Participants
|
Adverse Events
Placebo
GSK2798745
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=17 participants at risk
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
GSK2798745
n=16 participants at risk
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
|
|---|---|---|
|
Nervous system disorders
Headache
|
17.6%
3/17 • Number of events 3 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
43.8%
7/16 • Number of events 7 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Nervous system disorders
Lethargy
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Nervous system disorders
Migraine
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Gastrointestinal disorders
Diarrhoea
|
11.8%
2/17 • Number of events 2 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Gastrointestinal disorders
Vomiting
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Gastrointestinal disorders
Dyspepsia
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Ear and labyrinth disorders
Ear pain
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Ear and labyrinth disorders
Ear pruritus
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
General disorders
Fatigue
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
12.5%
2/16 • Number of events 2 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
General disorders
Feeling cold
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
General disorders
Suprapubic pain
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
11.8%
2/17 • Number of events 2 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Respiratory, thoracic and mediastinal disorders
Nasal pruritus
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Eye disorders
Visual impairment
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Eye disorders
Eye pain
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Infections and infestations
Oral herpes
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Infections and infestations
Upper respiratory tract infection
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/17 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
6.2%
1/16 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Injury, poisoning and procedural complications
Contusion
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
|
Psychiatric disorders
Sleep disorder
|
5.9%
1/17 • Number of events 1 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
0.00%
0/16 • AEs and SAEs were collected from the start of the treatment up to 45 days
AEs and SAEs were collected for All Subjects population
|
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