Clinical Trial Results:
A two-part trial to evaluate the safety, tolerability, clinical effect and systemic exposure potential of topically applied GSK2981278 ointment in subjects with plaque psoriasis
|
Summary
|
|
EudraCT number |
2016-002671-10 |
Trial protocol |
DE |
Global end of trial date |
05 May 2017
|
|
Results information
|
|
Results version number |
v3(current) |
This version publication date |
31 Jan 2019
|
First version publication date |
19 Apr 2018
|
Other versions |
v1 , v2 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
203820
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
GlaxoSmithKline
|
||
Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
|
||
Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
|
||
Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
07 Dec 2017
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
05 May 2017
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Part A: To evaluate the safety and tolerability of topically applied GSK2981278 and the systemic exposure of GSK2981278 following topical application in participants with plaque psoriasis. Part B: To evaluate the safety and tolerability of topically applied GSK2981278 and its vehicle and the clinical effect of topically applied GSK2981278 relative to vehicle control in participants with plaque psoriasis.
|
||
Protection of trial subjects |
To minimize the pain and discomfort associated with the punch biopsy procedure on the skin, local anesthesia was provided and the effect was checked by the physician before the procedure.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Feb 2017
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 8
|
||
Worldwide total number of subjects |
8
|
||
EEA total number of subjects |
8
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
6
|
||
From 65 to 84 years |
2
|
||
85 years and over |
0
|
||
|
|||||||
|
Recruitment
|
|||||||
Recruitment details |
Participants with chronic stable plaque psoriasis were recruited in this 2 part study to evaluate safety, tolerability and clinical effect of GSK2981278. | ||||||
|
Pre-assignment
|
|||||||
Screening details |
A total of 10 participants were screened; of which two were screen failures and eight were included in the treatment phase of Part A and received GSK2981278 4% ointment for 8 weeks. Part B of this study was not conducted as pre-defined efficacy criteria for continuing to Part B were not met. Hence no participants were enrolled in Part B. | ||||||
|
Period 1
|
|||||||
Period 1 title |
Overall Study (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
|
||||||
Blinding used |
Not blinded | ||||||
|
Arms
|
|||||||
|
Arm title
|
GSK2981278 4% | ||||||
Arm description |
Participants received 4% ointment of GSK2981278 twice daily for 8 weeks. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
GSK2981278
|
||||||
Investigational medicinal product code |
|||||||
Other name |
|||||||
Pharmaceutical forms |
Ointment
|
||||||
Routes of administration |
Topical use
|
||||||
Dosage and administration details |
GSK2981278 ointment was administered topically as a thin layer to all affected areas of the skin, twice daily, for 8 weeks.
|
||||||
|
|||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GSK2981278 4%
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received 4% ointment of GSK2981278 twice daily for 8 weeks. | |||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
GSK2981278 4%
|
||
Reporting group description |
Participants received 4% ointment of GSK2981278 twice daily for 8 weeks. | ||
|
|||||||||||
End point title |
Number of participants with on-therapy serious adverse events (SAEs) and non-SAEs: Part A [1] | ||||||||||
End point description |
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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. The analysis was performed on Safety analysis Population which comprised of all participants exposed to at least 1 application of study medication.
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
Up to Day 57
|
||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||
|
|||||||||||
| Notes [2] - Safety analysis Population |
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with application site tolerability assessment score during treatment period: Part A [3] | ||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The investigator assessed application site tolerability focusing on the treated non-lesional skin surrounding the plaques at each visit using the 5-point tolerability assessment scale ranging from 0 (no intolerance) to 4 (very severe intolerance). Number of participants in the corresponding score at Day 1, 15, 29 and 57 has been presented.
|
||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1, Day 15, Day 29, Day 57
|
||||||||||||||||||||||||||||||||||||||||||||||
| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||
| Notes [4] - Safety analysis Population |
|||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants with Negative Urinalysis Results: Part A [5] | ||||||||||||||||||||||||||||||||||||||
End point description |
Urine samples were collected from participants to evaluate urinalysis parameters including glucose, protein, erythrocytes and ketones. Number of participants with negative or normal urinalysis results at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values.
|
||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to Day 57
|
||||||||||||||||||||||||||||||||||||||
| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
| Notes [6] - Safety analysis Population |
|||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in Potential of hydrogen (pH) of urine: Part A [7] | ||||||||||||||
End point description |
The pH scale measures how acidic or basic a substance is. The pH scale ranges from 0 to 14. A pH of 7 is neutral. A pH less than 7 is acidic. A pH greater than 7 is basic. Urine samples were collected from participants and urine pH levels were assessed at Baseline, Day 15, Day 29 and Day 57. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||
| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||
|
|||||||||||||||
| Notes [8] - Safety analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in specific gravity of urine: Part A [9] | ||||||||||||||
End point description |
Urine samples were collected from participants and specific gravity levels were assessed at Baseline, Day 15, Day 29 and Day 57. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||
| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||
|
|||||||||||||||
| Notes [10] - Safety analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in blood urea nitrogen (BUN), glucose, potassium, sodium and calcium levels: Part A [11] | ||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical chemistry parameters including BUN, glucose, potassium, sodium and calcium. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||||||||||||||||||||||||||
| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
| Notes [12] - Safety analysis Population |
|||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||
End point title |
Change from Baseline in creatinine, total and direct bilirubin levels: Part A [13] | ||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical chemistry parameters including creatinine, total and direct bilirubin. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||||||||||||||
| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||
| Notes [14] - Safety analysis Population |
|||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||
End point title |
Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels: Part A [15] | ||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical chemistry parameters including AST, ALT and alkaline phosphatase. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||||||||||||||
| Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||
| Notes [16] - Safety analysis Population |
|||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Change from Baseline in protein and albumin levels: Part A [17] | ||||||||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical chemistry parameters including protein and albumin. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||||||||
| Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||
|
|||||||||||||||||||||
| Notes [18] - Safety analysis Population |
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in platelet, leukocyte, neutrophils, lymphocytes, monocytes, eosinophils and basophils levels: Part A [19] | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical hematology parameters including platelets, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Change from Baseline in clinical hematology parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [20] - Safety analysis Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in erythrocyte levels: Part A [21] | ||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical hematology parameters including erythrocytes. Change from Baseline in clinical hematology parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||
| Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||
|
|||||||||||||||
| Notes [22] - Safety analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in hemoglobin levels: Part A [23] | ||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical hematology parameters including hemoglobin. Change from Baseline in clinical hematology parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||
| Notes [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||
|
|||||||||||||||
| Notes [24] - Safety analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in hematocrit levels: Part A [25] | ||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical hematology parameters including hematocrit. Change from Baseline in clinical hematology parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||
| Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||
|
|||||||||||||||
| Notes [26] - Safety analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in mean corpuscular volume (MCV) levels: Part A [27] | ||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical hematology parameters including MCV. Change from Baseline in clinical hematology parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||
| Notes [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||
|
|||||||||||||||
| Notes [28] - Safety analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in mean corpuscular hemoglobin (MCH) levels: Part A [29] | ||||||||||||||
End point description |
Blood samples were collected from participants to evaluate clinical hematology parameters including MCH. Change from Baseline in clinical hematology parameters at Day 15, Day 29 and Day 57 are presented. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||
| Notes [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||
|
|||||||||||||||
| Notes [30] - Safety analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||||
End point title |
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels: Part A [31] | ||||||||||||||||||||
End point description |
Vital sign measurements including SBP and DBP were taken in a seated or supine position after 5-minutes of rest. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||||||||
| Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||
|
|||||||||||||||||||||
| Notes [32] - Safety analysis Population |
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in pulse rate levels: Part A [33] | ||||||||||||||
End point description |
Vital sign measurements including pulse rate were taken in a seated or supine position after 5-minutes of rest. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||
| Notes [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||
|
|||||||||||||||
| Notes [34] - Safety analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||
End point title |
Change from Baseline in Electrocardiogram (ECG) parameters including single RR heart rate: Part A [35] | ||||||||||||
End point description |
Single measurements of 12-lead ECG were obtained using an ECG machine to measure RR heart rate. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||
| Notes [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
| Notes [36] - Safety analysis Population |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Change from Baseline in ECG parameters including PR interval, QRS duration, QT interval, Corrected QT interval using Bazett’s formula (QTcB) and RR interval: Part A [37] | ||||||||||||||||||||||||||||
End point description |
Single measurements of 12-lead ECG were obtained using an ECG machine to measure PR interval, QRS duration, QT interval, QTcB and RR interval. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value
|
||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to Day 57
|
||||||||||||||||||||||||||||
| Notes [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Plasma concentration of GSK2981278 at nominal time: Part A [38] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK2981278. Non-quantifiable values in a profile occurring before the first measurable concentration were assigned a value of zero concentration. Single non-quantifiable values occurring between measurable concentrations in a profile were omitted. The analysis was performed on PK analysis Population which comprised of participants with at least one sample collected and analyzed for plasma drug concentration. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose, 1, 2, 4, 6, 8, 10 hours post-dose on Day 1, Day 29 and Day 57; Pre-dose, 2 hours post-dose on Day 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [39] - PK analysis Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||
End point title |
Mean percent change from Baseline in target plaque severity score (TPSS): Part A | ||||||||||||||
End point description |
The TPSS is the measure of clinical effect of GSK2981278. A target lesion of at least 9 centimeter square (cm^2) with a TPSS >=5 and an induration sub score >=2 was selected at Baseline. TPSS Total score was calculated by adding the individual scores of erythema, scaling, and induration (plaque thickness), assessed by the investigator on a 5-point scale ranging from 0=none to 4=very marked. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100. The analysis was performed on per protocol (PP) analysis Population which comprised of all participants eligible for treatment phase and who comply closely with the protocol.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline and up to Week 8
|
||||||||||||||
|
|||||||||||||||
| Notes [40] - PP analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Mean percent change from Baseline in Physician’s Global Assessment (PGA) score: Part A | ||||||||||||||
End point description |
The PGA is a clinical tool for assessing the current state/severity of a participant’s psoriasis. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, plaque thickness, and scaling as guidelines. The 5-point scale ranges from 0=clear to 4=severe. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline and up to Week 8
|
||||||||||||||
|
|||||||||||||||
| Notes [41] - PP analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Mean percent change from Baseline in Psoriasis Area and Severity Index (PASI) score: Part A | ||||||||||||||
End point description |
The PASI is a standard tool for assessing the severity of psoriasis that considers the overall severity of erythema, thickness, and scale, as well as the extent of body surface area (BSA) affected with psoriasis. The 3 clinical signs are each graded on a 5-point scale (0=none to 4=severe) and the percent BSA affected is scored on a 7-point scale (0= 0% skin with psoriasis to 6=>=90% skin with psoriasis) for each of the 4 specified body regions. The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. Higher scores indicate more severe disease. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline and up to Week 8
|
||||||||||||||
|
|||||||||||||||
| Notes [42] - PP analysis Population |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
|
Adverse events information
|
|||||||||||||||
Timeframe for reporting adverse events |
On-therapy SAEs and non-SAEs are presented from the start of study treatment up to Day 57.
|
||||||||||||||
Adverse event reporting additional description |
On-therapy SAEs and non-serious AEs are reported for members of the Safety analysis Population
|
||||||||||||||
Assessment type |
Systematic | ||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||
Dictionary version |
20.0
|
||||||||||||||
|
Reporting groups
|
|||||||||||||||
Reporting group title |
GSK2981278 4%
|
||||||||||||||
Reporting group description |
Participants received 4% ointment of GSK2981278 twice daily for 8 weeks. | ||||||||||||||
|
|||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||
|
|||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
13 Dec 2016 |
1. Psoriasis Symptom Diary revised to the original published version 2. Clarification of intent for urine sample analysis, minor text changes to Part A and B Time and Events tables to ensure consistency, and more comprehensive information on the allergic reaction risk. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
