Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Single and Repeated Doses of Topical GSK1278863 (NCT NCT01831804)
NCT ID: NCT01831804
Last Updated: 2019-08-19
Results Overview
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; or is associated with liver injury and impaired liver function.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
65 participants
Primary outcome timeframe
Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose])
Results posted on
2019-08-19
Participant Flow
This was a randomized, placebo-controlled, single-blind, parallel-group, two part (Part A and Part B) study in healthy volunteers (HVT) and participants with diabetic foot ulcer (DFU).
A total of 65 par. were randomized, however 2 par. did not receive study treatment and were excluded from analysis. All data tables reflect the total of treated par. (63).
Participant milestones
| Measure |
Placebo HVT (Cohort 1)
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
A/B (Cohort 1)
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
C/C (Cohort 2)
Participants with DFU were administered 0.1 percent of 25 milligrams per square centimeter (mg/cm\^2) GSK1278863 on intact skin in Period 1 followed by a wash-out period of at least 10 days. Participants were then administered a single dose of 0.1 percent of 25 mg/cm\^2 on wounded skin in Period 2.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E/E (Cohort 4)
A single dose of 1 percent of 100 mg/cm\^2 GSK1278863 was applied directly to wounded skin in Period 1, followed by application of a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 to intact skin. There was a wash-out period of at least 10 days between the two dosing periods.
|
Placebo DFU RD (Cohort 5)
Participants with DFU received once daily placebo application directly to the wounded skin for 14 days along with standard of care therapy.
|
R1r (Cohort 5)
Participants with DFU received once daily application of 1 percent of 100 mg/cm\^2 GSK1278863 to wounded skin for 14 days along with standard of care treatment.
|
Sr (Cohort 5)
Participants with DFU continued to receive daily application of standard of care wound treatment for 14 days.
|
|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
9
|
5
|
5
|
3
|
4
|
26
|
4
|
|
Overall Study
COMPLETED
|
3
|
1
|
3
|
5
|
3
|
3
|
3
|
23
|
2
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
6
|
0
|
2
|
0
|
1
|
3
|
2
|
Reasons for withdrawal
| Measure |
Placebo HVT (Cohort 1)
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
A/B (Cohort 1)
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
C/C (Cohort 2)
Participants with DFU were administered 0.1 percent of 25 milligrams per square centimeter (mg/cm\^2) GSK1278863 on intact skin in Period 1 followed by a wash-out period of at least 10 days. Participants were then administered a single dose of 0.1 percent of 25 mg/cm\^2 on wounded skin in Period 2.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E/E (Cohort 4)
A single dose of 1 percent of 100 mg/cm\^2 GSK1278863 was applied directly to wounded skin in Period 1, followed by application of a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 to intact skin. There was a wash-out period of at least 10 days between the two dosing periods.
|
Placebo DFU RD (Cohort 5)
Participants with DFU received once daily placebo application directly to the wounded skin for 14 days along with standard of care therapy.
|
R1r (Cohort 5)
Participants with DFU received once daily application of 1 percent of 100 mg/cm\^2 GSK1278863 to wounded skin for 14 days along with standard of care treatment.
|
Sr (Cohort 5)
Participants with DFU continued to receive daily application of standard of care wound treatment for 14 days.
|
|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
0
|
2
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Protocol defined stopping criteria
|
1
|
1
|
3
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Investigator discretion
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
|
Overall Study
Withdrew Consent
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
2
|
0
|
Baseline Characteristics
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Single and Repeated Doses of Topical GSK1278863
Baseline characteristics by cohort
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=3 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
A/B (Cohort 1)
n=9 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
C/C (Cohort 2)
n=5 Participants
Participants with DFU were administered 0.1 percent of 25 milligrams per square centimeter (mg/cm\^2) GSK1278863 on intact skin in Period 1 followed by a wash-out period of at least 10 days. Participants were then administered a single dose of 0.1 percent of 25 mg/cm\^2 on wounded skin in Period 2.
|
D (Cohort 3)
n=5 Participants
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E/E (Cohort 4)
n=3 Participants
A single dose of 1 percent of 100 mg/cm\^2 GSK1278863 was applied directly to wounded skin in Period 1, followed by application of a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 to intact skin. There was a wash-out period of at least 10 days between the two dosing periods.
|
Placebo DFU RD (Cohort 5)
n=4 Participants
Participants with DFU received once daily placebo application directly to the wounded skin for 14 days along with standard of care therapy.
|
R1r (Cohort 5)
n=26 Participants
Participants with DFU received once daily application of 1 percent of 100 mg/cm\^2 GSK1278863 to wounded skin for 14 days along with standard of care treatment.
|
Sr (Cohort 5)
n=4 Participants
Participants with DFU continued to receive daily application of standard of care wound treatment for 14 days.
|
Total
n=63 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
42.5 Years
STANDARD_DEVIATION 14.20 • n=5 Participants
|
53.0 Years
STANDARD_DEVIATION 8.72 • n=7 Participants
|
44.4 Years
STANDARD_DEVIATION 15.27 • n=5 Participants
|
52.6 Years
STANDARD_DEVIATION 5.90 • n=4 Participants
|
59.2 Years
STANDARD_DEVIATION 7.66 • n=21 Participants
|
48.3 Years
STANDARD_DEVIATION 11.93 • n=10 Participants
|
50.0 Years
STANDARD_DEVIATION 10.42 • n=115 Participants
|
55.5 Years
STANDARD_DEVIATION 6.13 • n=6 Participants
|
55.5 Years
STANDARD_DEVIATION 5.26 • n=6 Participants
|
51.2 Years
STANDARD_DEVIATION 9.4 • n=64 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
3 Participants
n=6 Participants
|
1 Participants
n=6 Participants
|
9 Participants
n=64 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
23 Participants
n=6 Participants
|
3 Participants
n=6 Participants
|
54 Participants
n=64 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage (Her.)
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
6 Participants
n=6 Participants
|
1 Participants
n=6 Participants
|
16 Participants
n=64 Participants
|
|
Race/Ethnicity, Customized
Japanese/East Asian Her./South East Asian Her.
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
0 Participants
n=6 Participants
|
1 Participants
n=64 Participants
|
|
Race/Ethnicity, Customized
White
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
4 Participants
n=115 Participants
|
19 Participants
n=6 Participants
|
3 Participants
n=6 Participants
|
46 Participants
n=64 Participants
|
PRIMARY outcome
Timeframe: Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose])Population: All Subject Population comprised of all participants who received at least one dose of study drug (including GSK1278863, placebo and standard care).
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; or is associated with liver injury and impaired liver function.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=9 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=3 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=5 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
n=5 Participants
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
n=3 Participants
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A)
AEs
|
2 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A)
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to a maximum of 53 days (Start of study treatment through final follow up 2 [28-32 days post last dose])Population: All Subject Population.
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; or is associated with liver injury and impaired liver function.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=26 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=4 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B)
AEs
|
2 Participants
|
5 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B)
SAEs
|
1 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose])Population: All Subject Population
ECG measurements were taken with the participants in supine position for at least 5 minutes. The number of participants with clinically significant abnormal ECG measurement following single dose administration for worst case post-Baseline visit has been presented.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=3 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=9 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=5 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
n=5 Participants
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
n=3 Participants
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to a maximum of 53 days (Start of study treatment through final follow up 2 [28-32 days post last dose])Population: All Subject Population
ECG measurements were taken with the participants in supine position for at least 5 minutes. The number of participants with clinically significant abnormal ECG measurement following single dose administration for worst case post-Baseline visit has been presented.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=26 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=4 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant 12-lead ECG Measurement Following Repeat Dose Administrations (Part B)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 (pre-dose and 48 hours) of Periods 1 and 2Population: All Subject Population
Vital sign measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Vital signs were measured after the participants rested in a supine or semi-supine position for 5 minutes prior to the procedure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=3 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=9 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=5 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
n=5 Participants
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
n=3 Participants
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
DBP Period 2; Day 1; 48 hours; Low; n=4,1,0,5,0,3
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
—
|
0 Participants
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
DBP Period 2; Day 1; 48 hours; High; n=4,1,0,5,0,3
|
0 Participants
|
1 Participants
|
—
|
0 Participants
|
—
|
1 Participants
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
SBP; Period 1; Day 1;pre-dose;Low;n=4,3,9,5,5,3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
SBP; Period 1; Day 1;pre-dose;High;n=4,3,9,5,5,3
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
SBP; Period 1; Day 1;48 hours;Low;n=4,3,8,5,4,3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
SBP; Period 1; Day 1;48 hours;High;n=4,3,8,5,4,3
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
SBP; Period 2; Day 1;pre-dose;Low;n=4,2,0,5,0,3
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
—
|
0 Participants
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
SBP; Period 2; Day 1;pre-dose;High;n=4,2,0,5,0,3
|
0 Participants
|
0 Participants
|
—
|
1 Participants
|
—
|
0 Participants
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
SBP; Period 2; Day 1;48 hours;Low;n=4,1,0,5,0,3
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
—
|
0 Participants
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
SBP; Period 2; Day 1;48 hours;High;n=4,1,0,5,0,3
|
0 Participants
|
0 Participants
|
—
|
1 Participants
|
—
|
1 Participants
|
PRIMARY outcome
Timeframe: Days 1 and 7 (pre-dose), Day 14 (24 hours)Population: All Subject Population
Vital sign measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Vital signs were measured after the participants rested in a supine or semi-supine position for 5 minutes prior to the procedure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=26 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=4 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)
DBP,Day 1,pre-dose,Low,n=4,26,4
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)
DBP,Day 1,pre-dose,High,n=4,26,4
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)
SBP,Day 1,pre-dose,Low, n=4,26,4
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)
SBP,Day 1,pre-dose,High, n=4,26,4
|
1 Participants
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)
SBP,Day 7,pre-dose,Low, n=4,25,4
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)
SBP,Day 7,pre-dose,High, n=4,25,4
|
0 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)
SBP,Day 14,24 H,Low, n=3,22,1
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)
SBP,Day 14,24 H,High, n=3,22,1
|
0 Participants
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose])Population: All Subject Population
A brief physical assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen) were planned to be performed by qualified licensed, medical professional (i.e., physician, physician assistant, or nurse practitioner) but was not performed.Since data was not collected, no analysis was performed.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to a maximum of 53 days (Start of study treatment through final follow up 2 [28-32 days post last dose])Population: All Subject Population
A brief physical assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen) were planned to be performed by qualified licensed, medical professional (i.e., physician, physician assistant, or nurse practitioner) but was not performed. Since data was not collected, no analysis was performed.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 (pre-dose)Population: All Subjects Population
Hematology parameters assessed were: platelet count, red blood cell count, white blood cell count, hemoglobin, reticulocyte count, hematocrit, absolute neutrophil count (ANC), monocytes, lymphocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. When a high or low value was reported, all values are presented for that time point and parameter.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=3 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=9 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=5 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
n=5 Participants
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
n=3 Participants
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A)
Total ANC,Day 1,pre-dose,Low
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A)
Total ANC,Day 1,pre-dose,High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 (pre-dose)Population: All Subjects Population
Hematology parameters assessed were: platelet count, red blood cell count, white blood cell count, hemoglobin, reticulocyte count, hematocrit, neutrophils, monocytes, lymphocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. When a high or low value was reported, all values are presented for that time point and parameter.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=26 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=4 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B)
Lymphocytes, Day 1,pre-dose,Low
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B)
Lymphocytes, Day 1,pre-dose,High
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 (pre-dose and 48 hours) in period 1; Day 1 (48 hours) in period 2Population: All Subjects Population
Chemistry parameters assessed were: Blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, creatine phosphokinase (CPK), potassium, chloride, total carbon dioxide (CO2), calcium, glycosylated hemoglobin (HbA1C), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyltransferase (GGT), Alkaline phosphatase (ALP), High sensitivity C-reactive protein (hsCRP), total and direct bilirubin, uric acid, albumin and total protein. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=3 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=9 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=5 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
n=5 Participants
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
n=3 Participants
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A)
Glucose,Day1,P1,pre-dose,low,n=4,3,9,5,5,3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A)
Glucose,Day1,P1,pre-dose,high,n=4,3,9,5,5,3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A)
Glucose,Day1,P1,48 H,low,n=4,3,8,5,4,3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A)
Glucose,Day1,P1,48 H,high,n=4,3,8,5,4,3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A)
Glucose,Day1,P2,48 H,low,n=4,1,0,5,0,3
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
—
|
0 Participants
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A)
Glucose,Day1,P2,48 H,high,n=4,1,0,5,0,3
|
0 Participants
|
0 Participants
|
—
|
1 Participants
|
—
|
2 Participants
|
PRIMARY outcome
Timeframe: Days 1 and 7 (pre-dose) and Day 14 (24 hours)Population: All Subjects Population
Chemistry parameters assessed were: Blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, creatine phosphokinase (CPK), potassium, chloride, total carbon dioxide (CO2), calcium, glycosylated hemoglobin (HbA1C), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyltransferase (GGT), Alkaline phosphatase (ALP), High sensitivity C-reactive protein (hsCRP), total and direct bilirubin, uric acid, albumin and total protein. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=4 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=26 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=4 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B)
Glucose,Day7,pre-dose,Low,n=4,24,4
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B)
Glucose,Day1,pre-dose,Low,n=4,26,4
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B)
Glucose,Day1,pre-dose,High,n=4,26,4
|
0 Participants
|
5 Participants
|
1 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B)
Glucose,Day7,pre-dose,High,n=4,24,4
|
0 Participants
|
7 Participants
|
2 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B)
Glucose,Day14,24H,Low,n=3,23,2
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B)
Glucose,Day14,24H,High,n=3,23,2
|
2 Participants
|
9 Participants
|
0 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hrs post-dosePopulation: All participants from whom a PK sample had been obtained and analyzed were included in the PK Population
The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Cmax could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=9 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=5 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=5 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=3 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of GSK1278863 (Part A)
|
NA Nanograms per milliliter (ng/mL)
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Nanograms per milliliter (ng/mL)
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Nanograms per milliliter (ng/mL)
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Nanograms per milliliter (ng/mL)
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14Population: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Cmax could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=26 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Cmax of GSK1278863 (Part B)
|
NA ng/mL
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dosePopulation: PK population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tmax could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=9 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=5 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=5 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=3 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Time of Occurrence of Cmax (Tmax) of GSK1278863 (Part A)
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14Population: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tmax could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=26 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Tmax of GSK1278863 (Part B)
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dosePopulation: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. t1/2 could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=9 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=5 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=5 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=3 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Apparent Terminal Elimination Half-life (t1/2) of GSK1278863 (Part A)
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14Population: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. t1/2 could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=26 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
t1/2 of GSK1278863 (Part B)
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dosePopulation: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tlag could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=9 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=5 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=5 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=3 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part A)
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification..
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14Population: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tlag could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=26 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part B)
|
NA Hour
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dosePopulation: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-inf) could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=9 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=5 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=5 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=3 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] of GSK1278863 (Part A)
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14Population: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-inf) could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=26 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
AUC(0-inf) of GSK1278863 (Part B)
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hrs post-dosePopulation: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-t) could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=9 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=5 Participants
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=5 Participants
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=3 Participants
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments [AUC(0-t)] of GSK1278863 (Part A)
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14Population: PK Population
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-t) could not be determined as data was below the limit of quantification.
Outcome measures
| Measure |
Placebo HVT (Cohort 1)
n=26 Participants
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
|---|---|---|---|---|---|---|
|
AUC(0-t) of GSK1278863 (Part B)
|
NA hour*nanograms/milliliter
Standard Deviation NA
NA indicates that data could not be determined as the data was below limit of quantification.
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Placebo HVT (Cohort 1)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
A/B (Cohort 1)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo DFU SD (Cohort 2, 3, 4)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
C (Cohort 2)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
D (Cohort 3)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
E (Cohort 4)
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo DFU RD (Cohort 5)
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
R1r (Cohort 5)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Sr (Cohort 5)
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo HVT (Cohort 1)
n=4 participants at risk
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=9 participants at risk
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=3 participants at risk
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=5 participants at risk
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
n=5 participants at risk
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
n=3 participants at risk
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
Placebo DFU RD (Cohort 5)
n=4 participants at risk
Participants with DFU received once daily placebo application directly to the wounded skin for 14 days along with standard of care therapy.
|
R1r (Cohort 5)
n=26 participants at risk
Participants with DFU received once daily application of 1 percent of 100 mg/cm\^2 GSK1278863 to wounded skin for 14 days along with standard of care treatment.
|
Sr (Cohort 5)
n=4 participants at risk
Participants with DFU continued to receive daily application of standard of care wound treatment for 14 days.
|
|---|---|---|---|---|---|---|---|---|---|
|
Infections and infestations
Arthritis bacterial
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/9 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
25.0%
1/4 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/26 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/9 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
33.3%
1/3 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
25.0%
1/4 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/26 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/9 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/26 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
25.0%
1/4 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
Other adverse events
| Measure |
Placebo HVT (Cohort 1)
n=4 participants at risk
Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods.
|
A/B (Cohort 1)
n=9 participants at risk
Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods.
|
Placebo DFU SD (Cohort 2, 3, 4)
n=3 participants at risk
Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods.
|
C (Cohort 2)
n=5 participants at risk
Participants with DFU were a single dose of 0.1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
D (Cohort 3)
n=5 participants at risk
Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin.
|
E (Cohort 4)
n=3 participants at risk
Participants with DFU were administered a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 on wounded skin.
|
Placebo DFU RD (Cohort 5)
n=4 participants at risk
Participants with DFU received once daily placebo application directly to the wounded skin for 14 days along with standard of care therapy.
|
R1r (Cohort 5)
n=26 participants at risk
Participants with DFU received once daily application of 1 percent of 100 mg/cm\^2 GSK1278863 to wounded skin for 14 days along with standard of care treatment.
|
Sr (Cohort 5)
n=4 participants at risk
Participants with DFU continued to receive daily application of standard of care wound treatment for 14 days.
|
|---|---|---|---|---|---|---|---|---|---|
|
Infections and infestations
Infected skin ulcer
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/9 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
25.0%
1/4 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/26 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
25.0%
1/4 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/9 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
33.3%
1/3 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
25.0%
1/4 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/26 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
11.1%
1/9 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
33.3%
1/3 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/26 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.0%
1/4 • Number of events 1 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
11.1%
1/9 • Number of events 2 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/5 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/3 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/26 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
0.00%
0/4 • SAEs and non-serious AEs were collected from start of study treatment through the final follow-up visit each of Part A {up to a maximum of 75 days (start of study treatment through final follow up 2 [28-32 days post last dose])} and B {up to a maximum of 53 days (start of study treatment through final follow up 2 [28-32 days post last dose])}
All Subject Population was used to assess AEs and SAEs
|
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