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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002671-10 | EudraCT Number |
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GSK2981278 is an inverse agonist of retinoic acid receptor-related orphan receptor (ROR) gamma. The aim of this study is to evaluate the safety, tolerability, clinical effect, and systemic exposure potential of topically applied GSK2981278 ointment in subjects with plaque psoriasis by treating all plaques on the body for 8 weeks. This single-center study will be conducted in two parts. Part A will be an open-label, single arm study and part B will be a double-blind, randomized, 2-arm, parallel-group, vehicle-controlled study. In Part A, 8 adult subjects and in Part B, 18 adult subjects with chronic stable plaque psoriasis will be enrolled. Total duration of study will be approximately 14 weeks. The results of this study will provide preliminary information about safety and efficacy of the drug and will help in providing the guidance for further development strategy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: GSK2981278 4% | Experimental | Subjects will receive topical application of GSK2981278 4% ointment twice daily for 8 weeks. Based on new safety information, the concentration of GSK2981278 may be lowered to 2% or 0.8%. |
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| Part B: GSK2981278 4% and vehicle | Experimental | In Part B, subjects will receive topical application of GSK2981278 4 % ointment or vehicle ointment twice daily for 8 weeks. Based on new safety information, the concentration of GSK2981278 may be lowered to 2% or 0.8%. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2981278 ointment | Drug | GSK2981278 ointment will be applied topically twice daily for 8 weeks to all subjects in Part A and to randomized subjects in Part B. GSK2981278 will be a white to off-white ointment and a thin layer will be applied to all affected areas for given timeframe. GSK2981278 is available as white to off-white ointment in unit strength 4% (w/w), 2% (w/w) and 0.8% (w/w), for topical application for application as thin layer to all affected areas . |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With On-treatment Serious Adverse Events (SAEs) and Non-SAEs: Part A | 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 effect, 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. | Up to Day 57 |
| Number of Participants With Application Site Tolerability Assessment Score During Treatment Period: Part A | 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. | Day 1, Day 15, Day 29, Day 57 |
| Number of Participants With Negative Urinalysis Results: Part A | 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. | Up to Day 57 |
| Change From Baseline in Potential of Hydrogen (pH) of Urine: Part A | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Percent Change From Baseline in Target Plaque Severity Score (TPSS): Part A | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| GSK Clinical Trials | GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Hamburg | 20095 | Germany |
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.
Participants with chronic stable plaque psoriasis were recruited in this 2 part study to evaluate safety, tolerability and clinical effect of GSK2981278.
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| ID | Title | Description |
|---|---|---|
| FG000 | GSK2981278 4%: Part A | Participants received 4% ointment of GSK2981278 twice daily for 8 weeks. |
| FG001 | GSK2981278 4%: Part B | Randomized participants were planned to receive 4% ointment of GSK2981278 twice daily for 8 weeks. |
| FG002 | Vehicle Ointment: Part B | Randomized participants were planned to receive vehicle ointment twice daily for 8 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A (Up to 14 Weeks) |
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| Part B (Up to 14 Weeks) |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | GSK2981278 4%: Part A | Participants received 4% ointment of GSK2981278 twice daily for 8 weeks. |
| BG001 | GSK2981278 4%: Part B | Randomized participants were planned to receive 4% ointment of GSK2981278 twice daily for 8 weeks. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With On-treatment Serious Adverse Events (SAEs) and Non-SAEs: Part A | 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 effect, 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. | Safety analysis Population | Posted | Number | Participants | Up to Day 57 |
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On-therapy SAEs and non-SAEs are presented from the start of study treatment up to Day 57.
On-therapy SAEs and non-serious AEs are reported for members of the Safety analysis Population. Data was not collected for Part B because no Participants were enrolled into this part of the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GSK2981278 4%: Part A | Participants received 4% ointment of GSK2981278 twice daily for 8 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COMMON COLD | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 13, 2016 | Jan 18, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 12, 2017 | Jan 18, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D011565 | Psoriasis |
| ID | Term |
|---|---|
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| Vehicle ointment | Drug | It will be supplied as white to off-white vehicle ointment for topical application. |
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| Baseline and up to Day 57 |
| Change From Baseline in Specific Gravity of Urine: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Blood Urea Nitrogen (BUN), Glucose, Potassium, Sodium and Calcium Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Creatinine, Total and Direct Bilirubin Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Protein and Albumin Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Platelet, Leukocyte, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Erythrocyte Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Hemoglobin Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Hematocrit Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Mean Corpuscular Volume (MCV) Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Mean Corpuscular Hemoglobin (MCH) Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Pulse Rate Levels: Part A | 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. | Baseline and up to Day 57 |
| Change From Baseline in Electrocardiogram (ECG) Parameters Including Single RR Heart Rate: Part A | 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 | Baseline and up to Day 57 |
| 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 | 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 | Baseline and up to Day 57 |
| Plasma Concentration of GSK2981278 at Nominal Time: Part A | 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). | 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 |
| Number of Participants With SAEs and Non-SAEs: Part B | 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 effect, other situations and is associated with liver injury or impaired liver function. The analysis was performed on Safety analysis set Population which comprised of all participants exposed to at least 1 application of study medication. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Up to Day 57 |
| Number of Participants With Application Site Tolerability Assessment Score During Treatment Period: Part B | The investigator planned to assess 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 with Application site tolerability assessment score were planned to be analyzed. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Up to Day 57 |
| Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline: Part B | Blood samples were planned to be collected for evaluation of clinical chemistry parameters. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as by subtracting post-Baseline visit values minus Baseline value. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Baseline and up to Week 57 |
| Number of Participants With Change in Hematology Toxicity Grade From Baseline: Part B | Blood samples were planned to be collected for the analysis of hematology parameters. 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. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Baseline and up to Day 57 |
| Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug: Part B | Vital sign measurement includes SBP, DBP, temperature, pulse rate. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Up to Day 57 |
| Number of Participants With Abnormal Findings for ECG Parameters: Part B | Single measurements of 12-lead ECGs were planned to be obtained using an ECG machine. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Up to Day 57 |
| Mean Percent Change in TPSS From Baseline to Week 8: Part B | The TPSS is the measure of clinical effect of GSK2981278. 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. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Baseline and up to Week 8 |
| Mean Percent Change in PGA Score From Baseline to Week 8: Part B | 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 by subtracting 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. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Baseline and up to Week 8 |
| Mean Percent Change in PASI From Baseline to Week 8: Part B | The PASI is a standard tool for assessing the severity of psoriasis that considers the overall severity of erythema, thickness, and scale, and 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). 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 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. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Baseline and up to Week 8 |
| Baseline and up to Week 8 |
| Mean Percent Change From Baseline in Physician's Global Assessment (PGA) Score: Part A | 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. | Baseline and up to Week 8 |
| Mean Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score: Part A | 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. | Baseline and up to Week 8 |
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| BG002 | Vehicle Ointment: Part B | Randomized participants were planned to receive vehicle ointment twice daily for 8 weeks. |
| BG003 | Total | Total of all reporting groups |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Primary | Number of Participants With Application Site Tolerability Assessment Score During Treatment Period: Part A | 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. | Safety analysis Population | Posted | Number | Participants | Day 1, Day 15, Day 29, Day 57 |
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| Primary | Number of Participants With Negative Urinalysis Results: Part A | 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. | Safety analysis Population | Posted | Number | Participants | Up to Day 57 |
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| Primary | Change From Baseline in Potential of Hydrogen (pH) of Urine: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Scores on a scale | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Specific Gravity of Urine: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Ratio | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Blood Urea Nitrogen (BUN), Glucose, Potassium, Sodium and Calcium Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Millimoles per liter (Mmol/L) | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Creatinine, Total and Direct Bilirubin Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Micromoles per liter (µmol/L) | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | International unit per liter (IU/L) | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Protein and Albumin Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Grams per liter (g/L) | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Platelet, Leukocyte, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | 10^9 cells/L | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Erythrocyte Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | 10^12 cells/L | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Hemoglobin Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | g/L | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Hematocrit Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Proportion of Red blood cells in blood | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Mean Corpuscular Volume (MCV) Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Femtoliter (fL) | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Mean Corpuscular Hemoglobin (MCH) Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Picograms (Pg) | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Millimeters of mercury (mmHg) | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Pulse Rate Levels: Part A | 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. | Safety analysis Population | Posted | Mean | Standard Deviation | Beats per minute | Baseline and up to Day 57 |
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| Primary | Change From Baseline in Electrocardiogram (ECG) Parameters Including Single RR Heart Rate: Part A | 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 | Safety analysis Population | Posted | Mean | Standard Deviation | Beats per minute | Baseline and up to Day 57 |
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| Primary | 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 | 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 | Safety analysis Population | Posted | Mean | Standard Deviation | Milliseconds (msec) | Baseline and up to Day 57 |
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| Primary | Plasma Concentration of GSK2981278 at Nominal Time: Part A | 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). | PK analysis Population | Posted | Mean | Standard Deviation | Picograms per milliliter (Pg/mL) | 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 |
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| Primary | Number of Participants With SAEs and Non-SAEs: Part B | 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 effect, other situations and is associated with liver injury or impaired liver function. The analysis was performed on Safety analysis set Population which comprised of all participants exposed to at least 1 application of study medication. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Safety analysis population. . Data was not collected for Part B as no Participants were enrolled into this part of the study. | Posted | Up to Day 57 |
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| Primary | Number of Participants With Application Site Tolerability Assessment Score During Treatment Period: Part B | The investigator planned to assess 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 with Application site tolerability assessment score were planned to be analyzed. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Safety analysis Population. Data was not collected for Part B as no Participants were enrolled into this part of the study. | Posted | Up to Day 57 |
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| Primary | Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline: Part B | Blood samples were planned to be collected for evaluation of clinical chemistry parameters. Last observation values collected prior to the first application of study treatment were considered as Baseline values. Change from Baseline was calculated as by subtracting post-Baseline visit values minus Baseline value. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Safety analysis Population. Data was not collected for Part B as no Participants were enrolled into this part of the study. | Posted | Baseline and up to Week 57 |
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| Primary | Number of Participants With Change in Hematology Toxicity Grade From Baseline: Part B | Blood samples were planned to be collected for the analysis of hematology parameters. 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. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Safety analysis Population. Data was not collected for Part B as no Participants were enrolled into this part of the study. | Posted | Baseline and up to Day 57 |
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| Primary | Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug: Part B | Vital sign measurement includes SBP, DBP, temperature, pulse rate. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Safety analysis Population. Data was not collected for Part B as no Participants were enrolled into this part of the study. | Posted | Up to Day 57 |
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| Primary | Number of Participants With Abnormal Findings for ECG Parameters: Part B | Single measurements of 12-lead ECGs were planned to be obtained using an ECG machine. This analysis was planned but not performed for Part B as the study was terminated during Part A. | Safety analysis Population. Data was not collected for Part B as no Participants were enrolled into this part of the study. | Posted | Up to Day 57 |
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| Primary | Mean Percent Change in TPSS From Baseline to Week 8: Part B | The TPSS is the measure of clinical effect of GSK2981278. 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. This analysis was planned but not performed for Part B as the study was terminated during Part A. | PP analysis Population. Data was not collected for Part B as no Participants were enrolled into this part of the study. | Posted | Baseline and up to Week 8 |
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| Primary | Mean Percent Change in PGA Score From Baseline to Week 8: Part B | 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 by subtracting 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. This analysis was planned but not performed for Part B as the study was terminated during Part A. | PP analysis Population. Data was not collected for Part B as no Participants were enrolled into this part of the study. | Posted | Baseline and up to Week 8 |
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| Primary | Mean Percent Change in PASI From Baseline to Week 8: Part B | The PASI is a standard tool for assessing the severity of psoriasis that considers the overall severity of erythema, thickness, and scale, and 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). 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 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. This analysis was planned but not performed for Part B as the study was terminated during Part A. | PP analysis Population. Data was not collected for Part B as no Participants were enrolled into this part of the study. | Posted | Baseline and up to Week 8 |
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| Secondary | Mean Percent Change From Baseline in Target Plaque Severity Score (TPSS): Part A | 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. | PP analysis Population | Posted | Mean | Standard Deviation | Percent change | Baseline and up to Week 8 |
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| Secondary | Mean Percent Change From Baseline in Physician's Global Assessment (PGA) Score: Part A | 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. | PP analysis Population | Posted | Mean | Standard Deviation | Percent change | Baseline and up to Week 8 |
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| Secondary | Mean Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score: Part A | 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. | PP analysis Population | Posted | Mean | Standard Deviation | Percent change | Baseline and up to Week 8 |
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| 0 |
| 8 |
| 0 |
| 8 |
| 1 |
| 8 |
| EG001 | GSK2981278 4%: Part B | Randomized participants were planned to receive 4% ointment of GSK2981278 twice daily for 8 weeks. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG002 | Vehicle Ointment: Part B | Randomized participants were planned to receive vehicle ointment twice daily for 8 weeks. | 0 | 0 | 0 | 0 | 0 | 0 |
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.
| Title | Measurements |
|---|---|
|
| Day 1; Grade 3 |
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| Day 1; Grade 4 |
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| Day 15; Grade 0 |
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| Day 15; Grade 1 |
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| Day 15; Grade 2 |
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| Day 15; Grade 3 |
|
| Day 15; Grade 4 |
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| Day 29; Grade 0 |
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| Day 29; Grade 1 |
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| Day 29; Grade 2 |
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| Day 29; Grade 3 |
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| Day 29; Grade 4 |
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| Day 57; Grade 0 |
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| Day 57; Grade 1 |
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| Day 57; Grade 2 |
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| Day 57; Grade 3 |
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| Day 57; Grade 4 |
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| Title | Measurements |
|---|---|
|
| Glucose; Day 57 |
|
| Protein; Baseline |
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| Protein; Day 15 |
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| Protein; Day 29 |
|
| Protein; Day 57 |
|
| Erythrocytes; Baseline |
|
| Erythrocytes; Day 15 |
|
| Erythrocytes; Day 29 |
|
| Erythrocytes; Day 57 |
|
| Ketones; Baseline |
|
| Ketones; Day 15 |
|
| Ketones; Day 29 |
|
| Ketones; Day 57 |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Glucose; Day 15 |
|
| Glucose; Day 29 |
|
| Glucose; Day 57 |
|
| Potassium; Day 15 |
|
| Potassium; Day 29 |
|
| Potassium; Day 57 |
|
| Sodium; Day 15 |
|
| Sodium; Day 29 |
|
| Sodium; Day 57 |
|
| Calcium; Day 15 |
|
| Calcium; Day 29 |
|
| Calcium; Day 57 |
|
| Title | Measurements |
|---|---|
|
| Total bilirubin; Day 15 |
|
| Total bilirubin; Day 29 |
|
| Total bilirubin; Day 57 |
|
| Direct bilirubin; Day 15 |
|
| Direct bilirubin; Day 29 |
|
| Direct bilirubin; Day 57 |
|
| Title | Measurements |
|---|---|
|
| ALT; Day 15 |
|
| ALT; Day 29 |
|
| ALT; Day 57 |
|
| Alkaline phosphatase; Day 15 |
|
| Alkaline phosphatase; Day 29 |
|
| Alkaline phosphatase; Day 57 |
|
| Title | Measurements |
|---|---|
|
| Albumin; Day 15 |
|
| Albumin; Day 29 |
|
| Albumin; Day 57 |
|
| Title | Measurements |
|---|---|
|
| Leukocytes; Day 15 |
|
| Leukocytes; Day 29 |
|
| Leukocytes; Day 57 |
|
| Neutrophils; Day 15 |
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| Neutrophils; Day 29 |
|
| Neutrophils; Day 57 |
|
| Lymphocytes; Day 15 |
|
| Lymphocytes; Day 29 |
|
| Lymphocytes; Day 57 |
|
| Monocytes; Day 15 |
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| Monocytes; Day 29 |
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| Monocytes; Day 57 |
|
| Eosinophils; Day 15 |
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| Eosinophils; Day 29 |
|
| Eosinophils; Day 57 |
|
| Basophils; Day 15 |
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| Basophils; Day 29 |
|
| Basophils; Day 57 |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| DBP; Day 15 |
|
| DBP; Day 29 |
|
| DBP: Day 57 |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| QRS duration; Day 57 |
|
| QT interval; Day 29 |
|
| QT interval; Day 57 |
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| QTcB interval; Day 29 |
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| QTcB interval; Day 57 |
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| RR interval; Day 29 |
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| RR interval; Day 57 |
|
|
| 2 hours post-dose; Day 1; n= 8 |
|
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| 4 hours post-dose; Day 1; n= 8 |
|
|
| 6 hours post-dose; Day 1; n= 8 |
|
|
| 8 hours post-dose; Day 1; n= 8 |
|
|
| 10 hours post-dose; Day 1; n= 8 |
|
|
| Pre-dose; Day 15; n= 7 |
|
|
| 2 hours post-dose; Day 15; n= 8 |
|
|
| Pre-dose; Day 29; n= 8 |
|
|
| 1 hour post-dose; Day 29; n= 8 |
|
|
| 2 hours post-dose; Day 29; n= 8 |
|
|
| 4 hours post-dose; Day 29; n= 8 |
|
|
| 6 hours post-dose; Day 29; n= 8 |
|
|
| 8 hours post-dose; Day 29; n= 7 |
|
|
| 10 hours post-dose; Day 29; n= 8 |
|
|
| Pre-dose; Day 57; n= 8 |
|
|
| 1 hour post-dose; Day 57; n= 8 |
|
|
| 2 hours post-dose; Day 57; n= 8 |
|
|
| 4 hours post-dose; Day 57; n= 8 |
|
|
| 6 hours post-dose; Day 57; n= 8 |
|
|
| 8 hours post-dose; Day 57; n= 8 |
|
|
| 10 hours post-dose; Day 57; n= 8 |
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|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|