Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Repeat Doses of GSK2982772 in Subjects With Psoriasis (NCT NCT02776033)
NCT ID: NCT02776033
Last Updated: 2020-07-08
Results Overview
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as 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, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study treatment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
65 participants
Primary outcome timeframe
Up to Day 116
Results posted on
2020-07-08
Participant Flow
This was a repeat dose study in participants with active plaque-type psoriasis. Participants received either GSK2982772 60 milligrams (mg) or placebo orally twice daily (BID) in Cohort 1 and either GSK2982772 60 mg or placebo orally three times daily (TID) in Cohort 2. The study was conducted at 4 centers in Canada.
A total of 100 participants were screened, of which, 65 participants were enrolled in the study.
Participant milestones
| Measure |
Placebo
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|
|
Overall Study
STARTED
|
18
|
23
|
24
|
|
Overall Study
COMPLETED
|
14
|
21
|
22
|
|
Overall Study
NOT COMPLETED
|
4
|
2
|
2
|
Reasons for withdrawal
| Measure |
Placebo
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
2
|
|
Overall Study
Physician Decision
|
2
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
|
Overall Study
Adverse Event
|
1
|
2
|
0
|
Baseline Characteristics
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Repeat Doses of GSK2982772 in Subjects With Psoriasis
Baseline characteristics by cohort
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
Total
n=65 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
47.1 Years
STANDARD_DEVIATION 14.95 • n=5 Participants
|
44.6 Years
STANDARD_DEVIATION 12.52 • n=7 Participants
|
47.5 Years
STANDARD_DEVIATION 13.41 • n=5 Participants
|
46.3 Years
STANDARD_DEVIATION 13.40 • n=4 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian - Central/South Asian Heritage
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian - East Asian Heritage
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian - South East Asian Heritage
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White - Arabic/North African Heritage
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
13 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to Day 116Population: Safety Population
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as 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, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study treatment.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
Any SAE
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
Any non-SAE
|
8 Participants
|
21 Participants
|
16 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to Day 116Population: Safety Population. Only those clinical chemistry parameters with data available per PCI criteria have been presented.
Blood samples were collected for analysis of clinical chemistry parameters. Clinical concern ranges were \>=2x Upper Limit of Normal (ULN) units per liter (U/L) for alanine aminotransferase (ALT), \<30 millimoles per liter (mmol/L) for albumin, \>=2x ULN U/L for alkaline phosphatase, \>=2x ULN U/L for aspartate aminotransferase (AST), \<2 or \>2.75 mmol/L for Calcium, \>44.2 mmol/L for Creatinine, \<3 or \>9 mmol/L for Glucose, \<3 or\>5.5 mmol/L for Potassium, \<130 or \>150 mmol/L for Sodium, and \>=1.5xULN micromoles per liter for total bilirubin. Participants were counted in worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (example given \[e.g.\], High to High), or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High', Baseline is defined as the latest pre-dose assessment.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
ALT; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
ALT; To Normal or No Change
|
18 Participants
|
22 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
ALT; To High
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Albumin; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Albumin; To Normal or No Change
|
18 Participants
|
23 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Albumin; To High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Alkaline phosphatase; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Alkaline phosphatase; To Normal or No Change
|
18 Participants
|
23 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Alkaline phosphatase; To High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
AST; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
AST; To Normal or No Change
|
18 Participants
|
23 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
AST; To High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Calcium; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Calcium; To Normal or No Change
|
18 Participants
|
23 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Calcium; To High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Creatinine; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Creatinine; To Normal or No Change
|
18 Participants
|
21 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Creatinine; To High
|
0 Participants
|
2 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Glucose; To Low
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Glucose; To Normal or No Change
|
16 Participants
|
22 Participants
|
23 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Glucose; To High
|
2 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Potassium; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Potassium; To Normal or No Change
|
18 Participants
|
22 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Potassium; To High
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Sodium; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Sodium; To Normal or No Change
|
18 Participants
|
23 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Sodium; To High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Total bilirubin; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Total bilirubin; To Normal or No Change
|
17 Participants
|
23 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Total bilirubin; To High
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to Day 116Population: Safety Population. Only those hematology parameters with data available per PCI criteria have been presented.
Blood samples were collected for analysis of hematology parameters. Clinical concern ranges were \>0.54 calculated as proportion of red blood cells in blood for Hematocrit, \>180 grams per liter for Hemoglobin, \<0.8 x10\^9 cells per liter for Lymphocytes, \<1.5 x10\^9 cells per liter for Neutrophil count, \<100 or \>550 x10\^9 cells per liter for Platelet count and \<3 or \>20 x10\^9 cells per liter White Blood Cell count. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Hematocrit; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Hematocrit; To Normal or No Change
|
18 Participants
|
23 Participants
|
22 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Hematocrit; To High
|
0 Participants
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Hemoglobin; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Hemoglobin; To Normal or No Change
|
17 Participants
|
23 Participants
|
23 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Hemoglobin; To High
|
1 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Lymphocytes; To Low
|
1 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Lymphocytes; To Normal or No Change
|
17 Participants
|
22 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Lymphocytes; To High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Neutrophil count; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Neutrophil count; To Normal or No Change
|
18 Participants
|
23 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Neutrophil count; To High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Platelet count; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Platelet count; To Normal or No Change
|
18 Participants
|
23 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Platelet count; To High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
White Blood Cell count; To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
White Blood Cell count; To Normal or No Change
|
18 Participants
|
23 Participants
|
24 Participants
|
—
|
|
Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
White Blood Cell count; To High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116)Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Urine samples were collected for measurement of urine pH at indicated time points. pH is a measure of hydrogen ion concentration and used to determine the acidity or alkalinity of urine. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Change From Baseline in Urine Potential of Hydrogen (pH)
DAY 8; n=18, 23, 22
|
0.69 Potential of hydrogen (pH)
Standard Deviation 0.788
|
-0.02 Potential of hydrogen (pH)
Standard Deviation 0.730
|
-0.11 Potential of hydrogen (pH)
Standard Deviation 0.786
|
—
|
|
Change From Baseline in Urine Potential of Hydrogen (pH)
DAY 15; n=17, 21, 22
|
0.56 Potential of hydrogen (pH)
Standard Deviation 0.609
|
0.14 Potential of hydrogen (pH)
Standard Deviation 0.673
|
-0.16 Potential of hydrogen (pH)
Standard Deviation 0.956
|
—
|
|
Change From Baseline in Urine Potential of Hydrogen (pH)
DAY 43; n=16, 21, 21
|
0.22 Potential of hydrogen (pH)
Standard Deviation 0.547
|
0.14 Potential of hydrogen (pH)
Standard Deviation 0.655
|
-0.36 Potential of hydrogen (pH)
Standard Deviation 1.108
|
—
|
|
Change From Baseline in Urine Potential of Hydrogen (pH)
DAY 85; n=14, 21, 22
|
0.29 Potential of hydrogen (pH)
Standard Deviation 0.975
|
0.00 Potential of hydrogen (pH)
Standard Deviation 0.592
|
-0.32 Potential of hydrogen (pH)
Standard Deviation 0.933
|
—
|
|
Change From Baseline in Urine Potential of Hydrogen (pH)
FOLLOW UP (Day 116); n=16, 22, 24
|
0.25 Potential of hydrogen (pH)
Standard Deviation 0.894
|
-0.07 Potential of hydrogen (pH)
Standard Deviation 0.541
|
-0.17 Potential of hydrogen (pH)
Standard Deviation 1.029
|
—
|
PRIMARY outcome
Timeframe: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116)Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Urine samples were collected to analyze specific gravity of urine. Specific gravity, is a measure of urine concentration and is measured using a chemical test. Specific gravity measurements provide a comparison of the amount of substances dissolved in urine as compared to pure water. If there were no solutes present, the specific gravity of urine would be 1.000 the same as pure water. Specific gravity between 1.002 and 1.035 could be considered as normal. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Change From Baseline in Urine Specific Gravity
DAY 8; n=18, 23, 22
|
-0.0043 Ratio
Standard Deviation 0.00765
|
-0.0020 Ratio
Standard Deviation 0.00704
|
0.0014 Ratio
Standard Deviation 0.00702
|
—
|
|
Change From Baseline in Urine Specific Gravity
DAY 15; n=17, 21, 22
|
-0.0029 Ratio
Standard Deviation 0.00679
|
-0.0028 Ratio
Standard Deviation 0.00567
|
0.0022 Ratio
Standard Deviation 0.00706
|
—
|
|
Change From Baseline in Urine Specific Gravity
DAY 43; n=16, 21, 21
|
-0.0032 Ratio
Standard Deviation 0.00692
|
0.0000 Ratio
Standard Deviation 0.00649
|
0.0001 Ratio
Standard Deviation 0.00694
|
—
|
|
Change From Baseline in Urine Specific Gravity
DAY 85; n=14, 21, 22
|
0.0004 Ratio
Standard Deviation 0.00560
|
-0.0022 Ratio
Standard Deviation 0.00608
|
0.0022 Ratio
Standard Deviation 0.00922
|
—
|
|
Change From Baseline in Urine Specific Gravity
FOLLOW UP (Day 116); n=16, 22, 24
|
-0.0016 Ratio
Standard Deviation 0.00719
|
-0.0020 Ratio
Standard Deviation 0.00739
|
0.0032 Ratio
Standard Deviation 0.00798
|
—
|
PRIMARY outcome
Timeframe: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Blood pressure was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; DAY 29; n=16, 22, 24
|
-1.4 Millimeter of mercury
Standard Deviation 8.52
|
-1.4 Millimeter of mercury
Standard Deviation 7.75
|
-1.2 Millimeter of mercury
Standard Deviation 7.92
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; DAY 43; n=16, 21, 23
|
-0.6 Millimeter of mercury
Standard Deviation 9.51
|
0.1 Millimeter of mercury
Standard Deviation 6.69
|
-1.8 Millimeter of mercury
Standard Deviation 6.10
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; DAY 57; n=14, 21, 22
|
-2.4 Millimeter of mercury
Standard Deviation 10.16
|
1.1 Millimeter of mercury
Standard Deviation 6.09
|
2.0 Millimeter of mercury
Standard Deviation 9.00
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; DAY 71; n=14, 21, 22
|
1.1 Millimeter of mercury
Standard Deviation 11.68
|
-1.3 Millimeter of mercury
Standard Deviation 8.12
|
-0.8 Millimeter of mercury
Standard Deviation 7.51
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; DAY 85; n=14, 21, 22
|
-0.6 Millimeter of mercury
Standard Deviation 7.44
|
-1.1 Millimeter of mercury
Standard Deviation 4.54
|
0.1 Millimeter of mercury
Standard Deviation 6.93
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; FOLLOW UP (Day 116); n=16, 22, 24
|
0.9 Millimeter of mercury
Standard Deviation 10.28
|
1.3 Millimeter of mercury
Standard Deviation 7.40
|
1.3 Millimeter of mercury
Standard Deviation 8.66
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; DAY 8; n=18, 23, 24
|
4.5 Millimeter of mercury
Standard Deviation 12.27
|
4.7 Millimeter of mercury
Standard Deviation 8.03
|
2.9 Millimeter of mercury
Standard Deviation 12.19
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; DAY 15; n=17, 22, 24
|
2.0 Millimeter of mercury
Standard Deviation 10.55
|
-1.0 Millimeter of mercury
Standard Deviation 8.91
|
-1.0 Millimeter of mercury
Standard Deviation 7.96
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; DAY 29; n=16, 22, 24
|
1.3 Millimeter of mercury
Standard Deviation 11.52
|
3.3 Millimeter of mercury
Standard Deviation 9.94
|
-1.3 Millimeter of mercury
Standard Deviation 13.26
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; DAY 43; n=16, 21, 23
|
-0.4 Millimeter of mercury
Standard Deviation 14.65
|
0.1 Millimeter of mercury
Standard Deviation 6.72
|
-2.2 Millimeter of mercury
Standard Deviation 10.51
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; DAY 57; n=14, 21, 22
|
-0.3 Millimeter of mercury
Standard Deviation 12.63
|
2.6 Millimeter of mercury
Standard Deviation 8.73
|
3.4 Millimeter of mercury
Standard Deviation 15.70
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; DAY 71; n=14, 21, 22
|
5.9 Millimeter of mercury
Standard Deviation 15.08
|
2.5 Millimeter of mercury
Standard Deviation 10.02
|
-1.0 Millimeter of mercury
Standard Deviation 12.95
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; DAY 85; n=14, 21, 22
|
4.4 Millimeter of mercury
Standard Deviation 10.36
|
2.9 Millimeter of mercury
Standard Deviation 9.52
|
-1.4 Millimeter of mercury
Standard Deviation 10.93
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; FOLLOW UP (Day 116); n=16, 22, 24
|
2.3 Millimeter of mercury
Standard Deviation 14.64
|
2.7 Millimeter of mercury
Standard Deviation 9.81
|
2.5 Millimeter of mercury
Standard Deviation 13.61
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; DAY 8; n=18, 23, 24
|
-0.4 Millimeter of mercury
Standard Deviation 10.07
|
0.0 Millimeter of mercury
Standard Deviation 5.72
|
1.4 Millimeter of mercury
Standard Deviation 6.88
|
—
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; DAY 15; n=17, 22, 24
|
-1.5 Millimeter of mercury
Standard Deviation 8.46
|
-0.5 Millimeter of mercury
Standard Deviation 6.68
|
-2.3 Millimeter of mercury
Standard Deviation 6.39
|
—
|
PRIMARY outcome
Timeframe: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Heart rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Change From Baseline in Heart Rate
DAY 8; n=18, 23, 24
|
2.8 Beats per minute
Standard Deviation 7.72
|
4.9 Beats per minute
Standard Deviation 10.54
|
2.3 Beats per minute
Standard Deviation 13.18
|
—
|
|
Change From Baseline in Heart Rate
DAY 15; n=17, 22, 24
|
1.5 Beats per minute
Standard Deviation 10.61
|
0.8 Beats per minute
Standard Deviation 8.43
|
1.9 Beats per minute
Standard Deviation 12.37
|
—
|
|
Change From Baseline in Heart Rate
DAY 29; n=16, 22, 24
|
1.0 Beats per minute
Standard Deviation 7.43
|
0.7 Beats per minute
Standard Deviation 9.61
|
4.0 Beats per minute
Standard Deviation 12.55
|
—
|
|
Change From Baseline in Heart Rate
DAY 43; n=16, 21, 23
|
0.2 Beats per minute
Standard Deviation 6.68
|
0.5 Beats per minute
Standard Deviation 7.64
|
4.9 Beats per minute
Standard Deviation 11.56
|
—
|
|
Change From Baseline in Heart Rate
DAY 57; n=14, 21, 22
|
2.9 Beats per minute
Standard Deviation 10.55
|
2.9 Beats per minute
Standard Deviation 10.42
|
5.3 Beats per minute
Standard Deviation 12.13
|
—
|
|
Change From Baseline in Heart Rate
DAY 71; n=14, 21, 22
|
1.6 Beats per minute
Standard Deviation 7.94
|
2.1 Beats per minute
Standard Deviation 8.81
|
2.4 Beats per minute
Standard Deviation 10.75
|
—
|
|
Change From Baseline in Heart Rate
DAY 85; n=14, 21, 22
|
0.9 Beats per minute
Standard Deviation 7.98
|
0.7 Beats per minute
Standard Deviation 8.63
|
1.9 Beats per minute
Standard Deviation 12.82
|
—
|
|
Change From Baseline in Heart Rate
FOLLOW UP (Day 116); n=16, 22, 24
|
3.5 Beats per minute
Standard Deviation 7.60
|
1.6 Beats per minute
Standard Deviation 10.28
|
5.1 Beats per minute
Standard Deviation 13.58
|
—
|
PRIMARY outcome
Timeframe: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Respiratory rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Change From Baseline in Respiratory Rate
DAY 8; n=18, 23, 24
|
-0.8 Breaths per minute
Standard Deviation 2.18
|
-0.4 Breaths per minute
Standard Deviation 2.81
|
0.3 Breaths per minute
Standard Deviation 2.86
|
—
|
|
Change From Baseline in Respiratory Rate
DAY 15; n=17, 22, 24
|
0.2 Breaths per minute
Standard Deviation 3.21
|
-0.6 Breaths per minute
Standard Deviation 2.44
|
-0.5 Breaths per minute
Standard Deviation 2.45
|
—
|
|
Change From Baseline in Respiratory Rate
DAY 29; n=16, 22, 24
|
0.9 Breaths per minute
Standard Deviation 3.34
|
-0.8 Breaths per minute
Standard Deviation 3.38
|
0.0 Breaths per minute
Standard Deviation 4.01
|
—
|
|
Change From Baseline in Respiratory Rate
DAY 43; n=16, 21, 23
|
-0.5 Breaths per minute
Standard Deviation 2.68
|
-0.4 Breaths per minute
Standard Deviation 3.06
|
0.3 Breaths per minute
Standard Deviation 3.50
|
—
|
|
Change From Baseline in Respiratory Rate
DAY 57; n=14, 21, 22
|
0.3 Breaths per minute
Standard Deviation 3.12
|
-0.5 Breaths per minute
Standard Deviation 2.36
|
-0.3 Breaths per minute
Standard Deviation 3.08
|
—
|
|
Change From Baseline in Respiratory Rate
DAY 71; n=14, 21, 22
|
0.2 Breaths per minute
Standard Deviation 3.09
|
-0.5 Breaths per minute
Standard Deviation 2.29
|
0.4 Breaths per minute
Standard Deviation 3.53
|
—
|
|
Change From Baseline in Respiratory Rate
DAY 85; n=14, 21, 22
|
0.3 Breaths per minute
Standard Deviation 3.31
|
-0.5 Breaths per minute
Standard Deviation 2.89
|
-0.3 Breaths per minute
Standard Deviation 3.76
|
—
|
|
Change From Baseline in Respiratory Rate
FOLLOW UP (Day 116); n=16, 22, 24
|
0.3 Breaths per minute
Standard Deviation 1.62
|
-0.1 Breaths per minute
Standard Deviation 2.60
|
-1.0 Breaths per minute
Standard Deviation 3.22
|
—
|
PRIMARY outcome
Timeframe: Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116)Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Body temperature was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Change From Baseline in Body Temperature
DAY 15; n=17, 22, 24
|
0.09 Celsius
Standard Deviation 0.466
|
-0.04 Celsius
Standard Deviation 0.358
|
0.17 Celsius
Standard Deviation 0.538
|
—
|
|
Change From Baseline in Body Temperature
DAY 29; n=16, 22, 24
|
-0.07 Celsius
Standard Deviation 0.447
|
-0.03 Celsius
Standard Deviation 0.387
|
0.01 Celsius
Standard Deviation 0.749
|
—
|
|
Change From Baseline in Body Temperature
DAY 8; n=18, 23, 24
|
0.12 Celsius
Standard Deviation 0.544
|
-0.11 Celsius
Standard Deviation 0.365
|
0.03 Celsius
Standard Deviation 0.656
|
—
|
|
Change From Baseline in Body Temperature
DAY 43; n=16, 21, 23
|
-0.14 Celsius
Standard Deviation 0.358
|
-0.01 Celsius
Standard Deviation 0.355
|
0.19 Celsius
Standard Deviation 0.757
|
—
|
|
Change From Baseline in Body Temperature
DAY 57; n=14, 21, 22
|
0.07 Celsius
Standard Deviation 0.705
|
0.11 Celsius
Standard Deviation 0.351
|
0.20 Celsius
Standard Deviation 0.646
|
—
|
|
Change From Baseline in Body Temperature
DAY 71; n=14, 21, 22
|
-0.01 Celsius
Standard Deviation 0.487
|
-0.17 Celsius
Standard Deviation 0.423
|
-0.07 Celsius
Standard Deviation 0.667
|
—
|
|
Change From Baseline in Body Temperature
DAY 85; n=14, 21, 22
|
0.06 Celsius
Standard Deviation 0.483
|
-0.03 Celsius
Standard Deviation 0.327
|
0.03 Celsius
Standard Deviation 0.562
|
—
|
|
Change From Baseline in Body Temperature
FOLLOW UP (Day 116); n=16, 22, 24
|
-0.05 Celsius
Standard Deviation 0.459
|
0.02 Celsius
Standard Deviation 0.505
|
0.07 Celsius
Standard Deviation 0.624
|
—
|
PRIMARY outcome
Timeframe: Up to Day 116Population: Safety Population
Single 12-lead electrocardiograms were obtained at indicated time points during the study using an electrocardiogram machine that automatically calculates the heart rate and measures PR, QRS, QT, QT interval corrected for heart rate (QTc) using Bazett's formula (QTcB) intervals and QTc using Fridericia's formula (QTcF). The abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Baseline is defined as the latest pre-dose assessment. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The number of participants with normal and abnormal electrocardiogram findings at any time post-Baseline visit has been presented.
Outcome measures
| Measure |
Placebo
n=18 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Number of Participants With Any Time Post-Baseline Results for Electrocardiogram Findings
Normal
|
7 Participants
|
8 Participants
|
7 Participants
|
—
|
|
Number of Participants With Any Time Post-Baseline Results for Electrocardiogram Findings
Abnormal-NCS
|
11 Participants
|
15 Participants
|
17 Participants
|
—
|
|
Number of Participants With Any Time Post-Baseline Results for Electrocardiogram Findings
Abnormal-CS
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 43 (Pre-dose) and Day 85Population: Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Blood samples were collected for pharmacokinetic analysis of GSK2982772 following 60 mg BID and 60 mg TID dose at indicated time points. The pharmacokinetic analysis was performed using non-compartmental methods. The analysis was based on Pharmacokinetic Population which comprised of participants in the 'Safety' Population for whom a pharmacokinetic sample was obtained and analyzed.
Outcome measures
| Measure |
Placebo
n=23 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Plasma Concentrations of GSK2982772 at Days 43 and 85
Pre-dose on Day 43; n=20, 23
|
16.905 Nanograms per milliliter
Standard Deviation 11.1855
|
70.422 Nanograms per milliliter
Standard Deviation 113.6397
|
—
|
—
|
|
Plasma Concentrations of GSK2982772 at Days 43 and 85
Day 85; n=20, 22
|
73.928 Nanograms per milliliter
Standard Deviation 160.0059
|
82.694 Nanograms per milliliter
Standard Deviation 152.4812
|
—
|
—
|
SECONDARY outcome
Timeframe: 1, 2, 4 and 6 Hours Post-dose on Days 1 and 43Population: Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Blood samples were collected for pharmacokinetic analysis of GSK2982772 following 60 mg BID and 60 mg TID dose at indicated time points. The pharmacokinetic analysis was performed using non-compartmental methods.
Outcome measures
| Measure |
Placebo
n=23 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
1 Hour Post-dose; Day 1; n=22, 24
|
702.547 Nanograms per milliliter
Standard Deviation 342.9405
|
681.675 Nanograms per milliliter
Standard Deviation 293.8436
|
—
|
—
|
|
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
2 Hours Post-dose; Day 1; n=22, 24
|
656.409 Nanograms per milliliter
Standard Deviation 244.9217
|
664.417 Nanograms per milliliter
Standard Deviation 198.8327
|
—
|
—
|
|
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
4 Hours Post-dose; Day 1; n=22, 24
|
262.377 Nanograms per milliliter
Standard Deviation 113.1955
|
249.583 Nanograms per milliliter
Standard Deviation 86.0919
|
—
|
—
|
|
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
6 Hours Post-dose; Day 1; n=22, 24
|
135.923 Nanograms per milliliter
Standard Deviation 67.9503
|
176.567 Nanograms per milliliter
Standard Deviation 194.8144
|
—
|
—
|
|
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
1 Hour Post-dose; Day 43; n=20, 23
|
639.420 Nanograms per milliliter
Standard Deviation 355.1716
|
858.261 Nanograms per milliliter
Standard Deviation 391.7822
|
—
|
—
|
|
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
2 Hours Post-dose; Day 43; n=20, 23
|
579.100 Nanograms per milliliter
Standard Deviation 134.6629
|
690.652 Nanograms per milliliter
Standard Deviation 187.1950
|
—
|
—
|
|
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
4 Hours Post-dose; Day 43; n=20, 23
|
309.700 Nanograms per milliliter
Standard Deviation 114.8441
|
304.348 Nanograms per milliliter
Standard Deviation 136.1582
|
—
|
—
|
|
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
6 Hours Post-dose; Day 43; n=20, 23
|
133.550 Nanograms per milliliter
Standard Deviation 68.6742
|
154.809 Nanograms per milliliter
Standard Deviation 124.4455
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Pre-dose on Day 1) and Day 43Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of Cluster of differentiation 11 (CD11+), CD161+, CD3+ and Elastase. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Data for all the listed biomarkers from skin biopsy has been presented for two skin types; dermis and epidermis at Day 43. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. NA indicates that data was not available as geometric coefficient of variation could not be calculated for single participant.
Outcome measures
| Measure |
Placebo
n=10 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=8 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
CD11+; Dermis; n=8, 7, 18 ,23
|
0.4 Percent change
Geometric Coefficient of Variation 44.6
|
-9.8 Percent change
Geometric Coefficient of Variation 61.9
|
-45.5 Percent change
Geometric Coefficient of Variation 127.8
|
-46.6 Percent change
Geometric Coefficient of Variation 93.6
|
|
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
CD11+; Epidermis; n=4 ,6, 10, 20
|
-29.7 Percent change
Geometric Coefficient of Variation 278.0
|
4.5 Percent change
Geometric Coefficient of Variation 176.8
|
-68.2 Percent change
Geometric Coefficient of Variation 191.6
|
-31.5 Percent change
Geometric Coefficient of Variation 157.6
|
|
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
CD161+; Dermis; n=7, 7, 13, 23
|
23.3 Percent change
Geometric Coefficient of Variation 148.2
|
-26.9 Percent change
Geometric Coefficient of Variation 49.5
|
-10.7 Percent change
Geometric Coefficient of Variation 73.4
|
-14.8 Percent change
Geometric Coefficient of Variation 65.7
|
|
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
CD161+; CD161+; Epidermis; n=1, 2 ,0, 4
|
-96.7 Percent change
Geometric Coefficient of Variation NA
NA indicates that data was not available as geometric coefficient of variation could not be calculated for single participant.
|
-29.3 Percent change
Geometric Coefficient of Variation 52.1
|
—
|
13.6 Percent change
Geometric Coefficient of Variation 51.0
|
|
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
CD3+; Dermis; n=8 ,7, 20, 23
|
-6.3 Percent change
Geometric Coefficient of Variation 52.1
|
4.9 Percent change
Geometric Coefficient of Variation 25.8
|
-36.2 Percent change
Geometric Coefficient of Variation 102.3
|
-26.0 Percent change
Geometric Coefficient of Variation 57.9
|
|
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
CD3+; Epidermis; n=8, 7, 20, 23
|
51.3 Percent change
Geometric Coefficient of Variation 68.9
|
87.8 Percent change
Geometric Coefficient of Variation 48.5
|
-40.9 Percent change
Geometric Coefficient of Variation 120.5
|
-33.6 Percent change
Geometric Coefficient of Variation 76.0
|
|
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
Elastase; Dermis; n=6, 5, 17, 19
|
-23.3 Percent change
Geometric Coefficient of Variation 46.1
|
-50.0 Percent change
Geometric Coefficient of Variation 96.4
|
-51.8 Percent change
Geometric Coefficient of Variation 778.4
|
-67.4 Percent change
Geometric Coefficient of Variation 527.3
|
|
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772
Elastase; Epidermis; n=4, 4, 4, 9
|
-27.3 Percent change
Geometric Coefficient of Variation 272.2
|
-60.8 Percent change
Geometric Coefficient of Variation 177.8
|
-36.6 Percent change
Geometric Coefficient of Variation 127.1
|
-63.1 Percent change
Geometric Coefficient of Variation 127.5
|
SECONDARY outcome
Timeframe: Baseline (Pre-dose on Day 1) and Day 43Population: Safety Population. Only those participants with data available at specified time point were analyzed.
A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of epidermis thickness. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses.
Outcome measures
| Measure |
Placebo
n=8 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=7 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=20 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy: Epidermis Thickness
|
-0.8 Percent change
Geometric Coefficient of Variation 36.4
|
-5.7 Percent change
Geometric Coefficient of Variation 25.7
|
-22.9 Percent change
Geometric Coefficient of Variation 46.4
|
-30.0 Percent change
Geometric Coefficient of Variation 46.0
|
SECONDARY outcome
Timeframe: Baseline (Pre-dose on Day 1) and Day 43Population: Safety Population
A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of K16 as keratin expression. Baseline is defined as the latest pre-dose assessment. Results for K16 were categorized as, negative to positive, no change and positive to negative at Day 43. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses.
Outcome measures
| Measure |
Placebo
n=10 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=8 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Number of Participants With Changes in Keratin 16 (K16) Histopathological Scoring in Psoriatic Lesional Biopsies
Negative to positive
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Changes in Keratin 16 (K16) Histopathological Scoring in Psoriatic Lesional Biopsies
No change
|
7 Participants
|
6 Participants
|
14 Participants
|
13 Participants
|
|
Number of Participants With Changes in Keratin 16 (K16) Histopathological Scoring in Psoriatic Lesional Biopsies
Positive to negative
|
1 Participants
|
1 Participants
|
4 Participants
|
10 Participants
|
|
Number of Participants With Changes in Keratin 16 (K16) Histopathological Scoring in Psoriatic Lesional Biopsies
Data missing
|
2 Participants
|
1 Participants
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 43Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
A target lesion for biopsy was identified on the trunk or extremities at indicated time points. mRNA expression of inflammatory markers and tissue healing were assessed. Data has been presented for inflammatory gene transcripts including interferon gamma, interleukin 10, interleukin 17A, interleukin 21, interleukin 22, interleukin 23 subunit alpha, interleukin 4 and tumor necrosis factor. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses.
Outcome measures
| Measure |
Placebo
n=10 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=8 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interferon gamma; Day 1; n=10,8,22,24
|
7535938.32 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 73.9
|
7224169.85 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 82.4
|
6855132.73 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 82.4
|
7502338.81 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 56.9
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interferon gamma; Day 43; n=8, 7, 21, 22
|
7467009.88 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 91.5
|
5426422.73 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 76.7
|
8560810.28 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 86.9
|
10082945.49 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 73.9
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 10; Day 1; n=10,8,22,24
|
5999323.22 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 53.3
|
11016442.52 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 25.4
|
6319300.05 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 49.7
|
9202484.60 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 58.2
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 10; Day 43; n=8, 7, 21, 22
|
5443660.53 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 69.8
|
8948437.47 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 37.2
|
6171220.22 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 55.7
|
10536204.86 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 59.4
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 17A; Day 1; n=10,8,22,24
|
10934904.83 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 168.5
|
6066981.63 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 247.0
|
7124531.63 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 123.0
|
9464750.94 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 65.8
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 17A; Day 43; n=8, 7, 21, 22
|
9978712.02 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 135.3
|
3694360.37 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 311.7
|
6506580.40 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 141.8
|
9161452.47 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 203.6
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 21; Day 1; n=10,8,22,24
|
1947669.71 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 129.0
|
1603798.85 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 163.3
|
1284591.79 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 109.9
|
1210894.24 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 93.1
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 21; Day 43; n=8, 7, 20, 22
|
1401657.00 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 125.0
|
1082550.27 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 133.2
|
1215077.05 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 106.4
|
1425030.28 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 153.4
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 22; Day 1; n=10,8,22,24
|
6561087.14 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 239.1
|
3042893.44 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 191.1
|
3365114.12 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 179.5
|
4229367.55 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 81.0
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 22; Day 43; n=8, 7, 21, 22
|
8431498.86 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 125.0
|
1447903.44 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 524.1
|
2845767.51 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 158.3
|
3457287.68 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 200.4
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 23 subunit alpha; Day 1; n=10,8,22,24
|
8747667.18 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 131.1
|
6133986.57 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 58.2
|
6380211.10 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 47.4
|
7006520.16 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 56.9
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 23 subunit alpha; Day 43; n=8,7,21,22
|
8552003.39 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 91.5
|
5420509.57 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 104.6
|
7441092.54 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 94.7
|
8918350.71 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 82.4
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 4; Day 1; n=10,8,22,24
|
461551.13 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 131.1
|
596608.00 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 102.9
|
800420.91 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 62.0
|
514256.12 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 75.3
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Interleukin 4; Day 43; n=7, 7, 21, 22
|
416943.25 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 144.1
|
492015.71 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 69.8
|
671471.18 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 75.3
|
438086.02 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 69.8
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Tumor necrosis factor; Day 1; n=10,8,22,24
|
43877326.09 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 38.3
|
63371891.45 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 35.0
|
44208132.84 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 27.5
|
63817136.53 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 42.8
|
|
Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772
Tumor necrosis factor; Day 43; n=8, 7, 21, 22
|
53240969.92 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 37.2
|
66678436.36 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 50.9
|
52197166.80 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 50.9
|
82816773.41 Copies per 25 nanogram RNA
Geometric Coefficient of Variation 47.4
|
SECONDARY outcome
Timeframe: Baseline (Pre-dose on Day 1) and Days 15, 29, 43, 57, 71, 85Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Two plaques were selected, one for clinical assessment (index plaque) and one for biopsy. Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using a scale ranging from 0 (no symptom) to 4 (very marked) with increasing score reflecting increased lesion severity. The PLSS is the sum of the erythema, scaling and plaque thickness scores. The total PLSS score ranged from 0 (no symptom) to 12 (very marked). Each lesion must have a PLSS score of \>=5. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all efficacy analyses.
Outcome measures
| Measure |
Placebo
n=10 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=8 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772
DAY 15; n=10, 7, 22, 24
|
-0.4 Percentage change
Standard Deviation 8.68
|
-9.6 Percentage change
Standard Deviation 15.79
|
-6.7 Percentage change
Standard Deviation 14.01
|
-7.8 Percentage change
Standard Deviation 18.05
|
|
Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772
DAY 29; n=9, 7, 22, 24
|
-8.7 Percentage change
Standard Deviation 15.84
|
-18.7 Percentage change
Standard Deviation 20.09
|
-14.3 Percentage change
Standard Deviation 21.13
|
-16.8 Percentage change
Standard Deviation 19.77
|
|
Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772
DAY 43; n=9, 7, 21, 23
|
-10.8 Percentage change
Standard Deviation 20.52
|
-22.6 Percentage change
Standard Deviation 24.24
|
-20.7 Percentage change
Standard Deviation 19.87
|
-27.4 Percentage change
Standard Deviation 18.08
|
|
Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772
DAY 57; n=8, 6, 21, 22
|
-11.3 Percentage change
Standard Deviation 24.41
|
-40.6 Percentage change
Standard Deviation 9.58
|
-25.5 Percentage change
Standard Deviation 23.09
|
-27.9 Percentage change
Standard Deviation 20.35
|
|
Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772
DAY 71; n=7, 7, 21 ,22
|
-13.3 Percentage change
Standard Deviation 21.66
|
-36.8 Percentage change
Standard Deviation 18.37
|
-34.4 Percentage change
Standard Deviation 28.24
|
-32.5 Percentage change
Standard Deviation 21.06
|
|
Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772
DAY 85; n=7, 7, 21 ,22
|
-20.6 Percentage change
Standard Deviation 15.95
|
-42.9 Percentage change
Standard Deviation 28.36
|
-30.4 Percentage change
Standard Deviation 22.20
|
-32.9 Percentage change
Standard Deviation 26.76
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 43, 57, 71 and 85Population: Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Two plaques were selected one for clinical assessment (index plaque) and one for biopsy. Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using a scale ranging from 0 (no symptom) to 4 (very marked) with increasing score reflecting increased lesion severity. The PLSS is the sum of the erythema, scaling and plaque thickness scores. The total PLSS score ranged from 0 (no symptom) to 12 (very marked). Each lesion must have a PLSS score of \>=5. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all efficacy analyses.
Outcome measures
| Measure |
Placebo
n=10 Participants
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=8 Participants
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=23 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg TID
n=24 Participants
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|---|
|
Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772
DAY 1; n=10, 8, 23, 24
|
6.9 Scores on a scale
Standard Deviation 1.73
|
8.5 Scores on a scale
Standard Deviation 1.51
|
8.1 Scores on a scale
Standard Deviation 1.62
|
7.5 Scores on a scale
Standard Deviation 1.44
|
|
Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772
DAY 15; n=10, 7, 22, 24
|
6.8 Scores on a scale
Standard Deviation 1.48
|
7.4 Scores on a scale
Standard Deviation 1.90
|
7.6 Scores on a scale
Standard Deviation 2.11
|
6.8 Scores on a scale
Standard Deviation 1.76
|
|
Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772
DAY 29; n=9, 7, 22, 24
|
6.3 Scores on a scale
Standard Deviation 1.80
|
6.6 Scores on a scale
Standard Deviation 1.62
|
7.0 Scores on a scale
Standard Deviation 2.30
|
6.2 Scores on a scale
Standard Deviation 1.91
|
|
Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772
DAY 43; n=9, 7, 21, 23
|
6.1 Scores on a scale
Standard Deviation 1.54
|
6.3 Scores on a scale
Standard Deviation 1.98
|
6.5 Scores on a scale
Standard Deviation 2.16
|
5.3 Scores on a scale
Standard Deviation 1.21
|
|
Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772
DAY 57; n=8, 6, 21, 22
|
6.3 Scores on a scale
Standard Deviation 1.49
|
4.8 Scores on a scale
Standard Deviation 1.47
|
6.2 Scores on a scale
Standard Deviation 2.40
|
5.2 Scores on a scale
Standard Deviation 1.37
|
|
Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772
DAY 71; n=7, 7, 21, 22
|
6.6 Scores on a scale
Standard Deviation 2.07
|
5.3 Scores on a scale
Standard Deviation 2.14
|
5.6 Scores on a scale
Standard Deviation 2.71
|
4.8 Scores on a scale
Standard Deviation 1.37
|
|
Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772
DAY 85; n=7 ,7 ,21, 22
|
6.0 Scores on a scale
Standard Deviation 1.53
|
4.9 Scores on a scale
Standard Deviation 2.73
|
5.8 Scores on a scale
Standard Deviation 2.28
|
4.8 Scores on a scale
Standard Deviation 1.92
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
GSK2982772 60 mg BID
Serious events: 1 serious events
Other events: 21 other events
Deaths: 1 deaths
GSK2982772 60 mg TID
Serious events: 1 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=18 participants at risk
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 participants at risk
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 participants at risk
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.3%
1/23 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Injury, poisoning and procedural complications
Procedural hypertension
|
0.00%
0/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.2%
1/24 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
Other adverse events
| Measure |
Placebo
n=18 participants at risk
Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study.
|
GSK2982772 60 mg BID
n=23 participants at risk
Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study.
|
GSK2982772 60 mg TID
n=24 participants at risk
Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study.
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
22.2%
4/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
30.4%
7/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
29.2%
7/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Nervous system disorders
Headache
|
22.2%
4/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
43.5%
10/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
12.5%
3/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.3%
1/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
8.3%
2/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
2/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.2%
1/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
8.7%
2/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.2%
1/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
2/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.3%
1/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
General disorders
Fatigue
|
0.00%
0/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
13.0%
3/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Gastrointestinal disorders
Nausea
|
5.6%
1/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.3%
1/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.2%
1/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
8.7%
2/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.2%
1/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
8.7%
2/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
8.7%
2/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
5.6%
1/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.2%
1/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.6%
1/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.3%
1/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
1/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
4.3%
1/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Nervous system disorders
Somnolence
|
5.6%
1/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Infections and infestations
Tonsillitis
|
5.6%
1/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
5.6%
1/18 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/23 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
|
0.00%
0/24 • Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety 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