Trial Outcomes & Findings for A Study to Test the Effect of 2 Different Doses of Topical GW870086X on Atopic Dermatitis Also Including a Postive Control and a Placebo (NCT NCT01299610)
NCT ID: NCT01299610
Last Updated: 2017-11-17
Results Overview
Three target lesions were selected and each of the 3 target lesions were assessed separately using the TIS for erythema, oedema/papulation, and excoriation using a score of 0 - 3 as 0 = absent, 1 = mild, 2 = moderate, 3 = severe. Each participant had at least 3 index lesions (=\> 1square centimeter in size) with a sum score of =\>4 and =\< 6 for erythema, oedema/populations and excoriations using the TIS rating scale at screening. The index lesions represented common lesions i.e. not the most or least severe lesions. The total TIS score for a lesion was calculated as the sum of each of the component scores i.e. ranging from 0 (no symptoms) to 9 (severe symptoms). The values of Day 1 assessments were considered as Baseline values. The change from Baseline was calculated by subtracting the Baseline TIS score from Day 22 TIS score.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Baseline (Day 1) and Day 22
Results posted on
2017-11-17
Participant Flow
The study was conducted at one center in Germany between 13 December 2010 and 14 April 2011.
Twenty five participants were randomized and completed the study.
Participant milestones
| Measure |
Treatment 1: GW870086, 2.0%, GW870086, 0.2% and Placebo
Participants applied GW870086 2.0% cream, GW870086 0.2% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and the study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of the pots, the use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. The participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Treatment 2: GW870086 2.0%, FP 0.05% and Placebo
Participants applied GW870086 2.0% cream, Fluticasone Propionate (FP) 0.05% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Treatment 3: GW870086 0.2%, FP 0.05% and Placebo
Participants applied GW870086 0.2% cream, FP 0.05% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
5
|
10
|
|
Overall Study
COMPLETED
|
10
|
5
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Test the Effect of 2 Different Doses of Topical GW870086X on Atopic Dermatitis Also Including a Postive Control and a Placebo
Baseline characteristics by cohort
| Measure |
Treatment 1: GW870086, 2.0%, GW870086, 0.2% and Placebo
n=10 Participants
Participants applied GW870086, 2.0% cream, GW870086, 0.2% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and the study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of the pots, the use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. The participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Treatment 2: GW870086 2.0%, FP 0.05% and Placebo
n=5 Participants
Participants applied GW870086, 2.0% cream, Fluticasone Propionate (FP) 0.05% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Treatment 3: GW870086 0.2%, FP 0.05% and Placebo
n=10 Participants
Participants applied GW870086, 0.2% cream, FP, 0.05% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
41.9 Years
STANDARD_DEVIATION 18.81 • n=5 Participants
|
40.8 Years
STANDARD_DEVIATION 19.43 • n=7 Participants
|
28.3 Years
STANDARD_DEVIATION 10.15 • n=5 Participants
|
36.2 Years
STANDARD_DEVIATION 16.68 • n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and Day 22Population: The Efficacy Population was defined as participants in the 'All Subjects' population with at least one post dose TIS assessment.
Three target lesions were selected and each of the 3 target lesions were assessed separately using the TIS for erythema, oedema/papulation, and excoriation using a score of 0 - 3 as 0 = absent, 1 = mild, 2 = moderate, 3 = severe. Each participant had at least 3 index lesions (=\> 1square centimeter in size) with a sum score of =\>4 and =\< 6 for erythema, oedema/populations and excoriations using the TIS rating scale at screening. The index lesions represented common lesions i.e. not the most or least severe lesions. The total TIS score for a lesion was calculated as the sum of each of the component scores i.e. ranging from 0 (no symptoms) to 9 (severe symptoms). The values of Day 1 assessments were considered as Baseline values. The change from Baseline was calculated by subtracting the Baseline TIS score from Day 22 TIS score.
Outcome measures
| Measure |
GW870086, 0.2% Cream
n=20 Participants
Participants applied GW870086, 0.2% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
GW870086, 2.0% Cream
n=15 Participants
Eligible participants applied GW870086, 2.0% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Placebo
n=25 Participants
Eligible participants applied matching placebo to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
FP, 0.05% Cream
n=15 Participants
Eligible participants applied FP, 0.05% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
|---|---|---|---|---|
|
Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at Day 22
|
-1.99 Score on scale
Standard Error 0.418
|
-2.49 Score on scale
Standard Error 0.465
|
-1.61 Score on scale
Standard Error 0.380
|
-3.11 Score on scale
Standard Error 0.467
|
SECONDARY outcome
Timeframe: Days 2, 3, 7, and 14Population: Efficacy Population
Three target lesions were selected and each of the 3 target lesions were assessed separately using the TIS for erythema, oedema/papulation, and excoriation using a score of 0 - 3 as 0 = absent, 1 = mild, 2 = moderate, 3 = severe. Each participant had at least 3 index lesions (=\> 1square centimeter in size) with a sum score of =\>4 and =\< 6 for erythema, oedema/populations and excoriations using the TIS rating scale at screening. The index lesions represented common lesions i.e. not the most or least severe lesions. The total TIS score for a lesion was calculated as the sum of each of the component scores i.e. may range from 0 (no symptoms) to 9 (severe symptoms). The values of Day 1 assessments were considered as Baseline values. The change from Baseline was calculated by subtracting the Baseline TIS score from Day 22 values TIS score.
Outcome measures
| Measure |
GW870086, 0.2% Cream
n=20 Participants
Participants applied GW870086, 0.2% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
GW870086, 2.0% Cream
n=15 Participants
Eligible participants applied GW870086, 2.0% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Placebo
n=25 Participants
Eligible participants applied matching placebo to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
FP, 0.05% Cream
n=15 Participants
Eligible participants applied FP, 0.05% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
|---|---|---|---|---|
|
Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14
Day 2
|
-0.37 Score on scale
Standard Error 0.19
|
-0.53 Score on scale
Standard Error 0.203
|
-0.45 Score on scale
Standard Error 0.181
|
-0.62 Score on scale
Standard Error 0.203
|
|
Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14
Day 3
|
-0.91 Score on scale
Standard Error 0.266
|
-0.80 Score on scale
Standard Error 0.291
|
-0.94 Score on scale
Standard Error 0.246
|
-1.22 Score on scale
Standard Error 0.292
|
|
Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14
Day 7
|
-1.43 Score on scale
Standard Error 0.363
|
-1.78 Score on scale
Standard Error 0.403
|
-1.19 Score on scale
Standard Error 0.331
|
-2.47 Score on scale
Standard Error 0.405
|
|
Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14
Day 14
|
-1.82 Score on scale
Standard Error 0.367
|
-2.23 Score on scale
Standard Error 0.408
|
-1.58 Score on scale
Standard Error 0.335
|
-2.97 Score on scale
Standard Error 0.409
|
SECONDARY outcome
Timeframe: Days 2, 3, 7, 14 and 22Population: Efficacy population
Three target lesions were selected and each of the 3 target lesions were assessed separately using the IGA. The IGA was carried out by a trained dermatologist and score ranged from 0 to 5. The detailed IGA scale is as: 0-Clear: No inflammatory signs of atopic dermatitis, 1- Almost clear: Just perceptible erythema and just perceptible apulation/infiltration, 2-Mild: Mild erythema and mild papulation/infiltration, 3-Moderate: Moderate erythema, and moderate papulation/infiltration, 4-Severe: Severe erythema and severe papulation/infiltration, 5-Very Severe: Very severe erythema, and very severe papulation/infiltration with oozing/crusting. The participant was considered as responder if each lesion at timepoint, IGA score reduced by 1 grade and improved from Baseline by 2 grades.
Outcome measures
| Measure |
GW870086, 0.2% Cream
n=20 Participants
Participants applied GW870086, 0.2% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
GW870086, 2.0% Cream
n=15 Participants
Eligible participants applied GW870086, 2.0% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Placebo
n=25 Participants
Eligible participants applied matching placebo to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
FP, 0.05% Cream
n=15 Participants
Eligible participants applied FP, 0.05% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
|---|---|---|---|---|
|
Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22
Day 2
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22
Day 3
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22
Day 7
|
3 Participants
|
1 Participants
|
1 Participants
|
6 Participants
|
|
Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22
Day 14
|
8 Participants
|
2 Participants
|
4 Participants
|
6 Participants
|
|
Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22
Day 22
|
6 Participants
|
4 Participants
|
7 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Upto Day 21Population: All Subjects Population was defined as all participants who had at least one application of placebo, GW870086X 0.2%, GW 870086X 2% or FP 0.05% cream.
AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Number of participants with AEs and SAEs were reported.
Outcome measures
| Measure |
GW870086, 0.2% Cream
n=10 Participants
Participants applied GW870086, 0.2% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
GW870086, 2.0% Cream
n=5 Participants
Eligible participants applied GW870086, 2.0% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Placebo
n=10 Participants
Eligible participants applied matching placebo to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
FP, 0.05% Cream
Eligible participants applied FP, 0.05% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
|---|---|---|---|---|
|
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any AEs
|
6 Participants
|
2 Participants
|
5 Participants
|
—
|
|
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to Day 21Population: All subject population
Laboratory ranges of PCI represented as multiplier of lower limit of normal \[LLN\]; Multipliers of upper limit of normal (ULN). Laboratory ranges of PCI for white blood cell count (0.67×LLN; 1.82×ULN), neutrophil count (0.83×ULN), hemoglobin for male (1.03×ULN) and for female (1.13×ULN), hematocrit for male (1.02×ULN) for female (1.17×ULN), platelet count (0.67×LLN; 1.57), lymphocytes (0.81×LLN), albumin (0.86 ×LLN), calcium (0.91×LLN; 1.06×ULN), glucose (0.71×LLN; 1.41×ULN), potassium (0.86×LLN; 1.10×ULN), sodium (0.96×LLN; 1.03×ULN), aspartate amino transferase (\>= 2x ULN), alanine transaminase (\>=2x ULN), alkaline Phosphatase (\>=2x ULN), total bilirubin (\>=1.5x ULN). Only those parameters for which at least one value of PCI was reported are summarized. The number of participants with PCI hematology and clinical chemistry findings at any visit during the treatment and follow-up were reported.
Outcome measures
| Measure |
GW870086, 0.2% Cream
n=10 Participants
Participants applied GW870086, 0.2% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
GW870086, 2.0% Cream
n=5 Participants
Eligible participants applied GW870086, 2.0% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Placebo
n=10 Participants
Eligible participants applied matching placebo to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
FP, 0.05% Cream
Eligible participants applied FP, 0.05% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI)
Lymphocyte, Low
|
1 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI)
Total Neutrophils, Low
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI)
AST, High
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI)
Glucose, Low
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to Day 21Population: All subject population
12-lead ECG was obtained. The standard ECG criteria of PCI were 1) absolute QTc Interval, \> 450 milliseconds (msec), 2) increase from Baseline in QTc \> 60 msec 3) absolute PR Interval, \<110 and \>220 msec, 4) absolute QRS Interval, \< 75 and \>110 msec. The number of participants with PCI ECG findings at any visit during the treatment and follow-up were reported.
Outcome measures
| Measure |
GW870086, 0.2% Cream
n=10 Participants
Participants applied GW870086, 0.2% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
GW870086, 2.0% Cream
n=5 Participants
Eligible participants applied GW870086, 2.0% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Placebo
n=10 Participants
Eligible participants applied matching placebo to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
FP, 0.05% Cream
Eligible participants applied FP, 0.05% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram (ECG) of PCI
|
1 Participants
|
1 Participants
|
1 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to Day 21Population: All subject population
The PCI ranges (low and high) of the vital sign parameters were for systolic blood pressure (\<85 and \>160 millimeter of mercury \[mmHg\]), diastolic blood pressure (\<45 and \>100 mmHg) and heart rate (\<40 and \>110 beats per minute). Only those parameters for which at least one value of PCI was reported are summarized. There were no values of PCI in vital signs parameters over the course of the study.
Outcome measures
| Measure |
GW870086, 0.2% Cream
n=10 Participants
Participants applied GW870086, 0.2% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
GW870086, 2.0% Cream
n=5 Participants
Eligible participants applied GW870086, 2.0% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Placebo
n=10 Participants
Eligible participants applied matching placebo to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
FP, 0.05% Cream
Eligible participants applied FP, 0.05% cream to a specific lesion located on the arms and/or legs every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Vital Signs (Systolic and Diastolic Blood Pressure and Pulse Rate) of PCI
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 7, 14 and 21Population: Pharmacokinetic population was defined as participants in the All Subjects population for whom a pharmacokinetic sample was obtained and analyzed. Cmax was not analysed because the plasma concentrations were not quantifiable.
Cmax was planned to be determined directly from the raw concentration-time data. The pharmacokinetic parameters were planned to be calculated by standard non-compartmental analysis using Win-Nonlin Pro-Version 5.2 or higher.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 7, 14 and 21Population: Pharmacokinetics population. Tmax was not analysed because the plasma concentrations were not quantifiable.
Tmax was planned to be determined directly from the raw concentration-time data. The pharmacokinetic parameters were planned to be calculated by standard non-compartmental analysis using Win-Nonlin Pro-Version 5.2 or higher.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 7, 14 and 21Population: Pharmacokinetics population. AUC was not analyzed because the plasma concentrations were not quantifiable.
The area under the plasma concentration-time curve to the last quantifiable concentration (AUC\[0-t\]) and area under the plasma concentration-time curve over the dosing interval (AUC\[0-tou\]) was planned to be determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The pharmacokinetic parameters were planned to be calculated by standard non-compartmental analysis using Win-Nonlin Pro-Version 5.2 or higher.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 and Day 22Population: Efficacy Population
A 4 millimeter (mm) punch skin biopsy was taken pre- and post-treatment (Day 1 and Day 21) from each of the 3 index lesions. The results were not analyzed for this outcome measure.
Outcome measures
Outcome data not reported
Adverse Events
Treatment 1: GW870086, 2.0%, GW870086, 0.2% and Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Treatment 2: GW870086 2.0%, FP 0.05% and Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Treatment 3: GW870086 0.2%, FP 0.05% and Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment 1: GW870086, 2.0%, GW870086, 0.2% and Placebo
n=10 participants at risk
Participants applied GW870086, 2.0% cream, GW870086, 0.2% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and the study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of the pots, the use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. The participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Treatment 2: GW870086 2.0%, FP 0.05% and Placebo
n=5 participants at risk
Participants applied GW870086, 2.0% cream, Fluticasone Propionate (FP) 0.05% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
Treatment 3: GW870086 0.2%, FP 0.05% and Placebo
n=10 participants at risk
Participants applied GW870086, 0.2% cream, FP, 0.05% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
20.0%
2/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
20.0%
2/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
|
Nervous system disorders
Dizziness
|
0.00%
0/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
40.0%
2/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
|
Infections and infestations
Gastroenteritis norovirus
|
0.00%
0/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
10.0%
1/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
1/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
1/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
10.0%
1/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
10.0%
1/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
10.0%
1/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
|
Cardiac disorders
Tachycardia
|
10.0%
1/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
10.0%
1/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
0.00%
0/5 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
10.0%
1/10 • AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
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