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Clinical Trial Results:
A multi-centre, randomised, double-blind, placebo-controlled, dose ranging study to evaluate the safety and efficacy of GSK2586184 in patients with chronic plaque psoriasis

Summary
EudraCT number	2012-002917-20
Trial protocol	GB DE
Global end of trial date	24 Mar 2014

Results information
Results version number	v1(current)
This version publication date	15 Mar 2016
First version publication date	27 May 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

JAK116679

ISRCTN number

US NCT number

NCT01782664

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, +1 8664357343,

Scientific contact

GSK Response Center, GlaxoSmithKline, +1 8664357343,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

02 May 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

24 Mar 2014

Was the trial ended prematurely?

Main objective of the trial

To estimate the relationship between dose of GSK2586184 and clinical response as assessed by PASI score after 12 weeks of treatment in patients with moderate to severe plaque-type psoriasis.

Protection of trial subjects

Measures to protect trial subjects: • Routine safety monitoring (safety laboratory tests, physical examinations, vital signs and ECGs) to detect any adverse reactions, and in particular, regular AE checks and temperature monitoring to detect any signs of infection. • Study specific withdrawal criteria for changes in haematological parameters, renal function, liver chemistry, QTc, infection, adverse events and worsening of psoriasis symptoms. • Ongoing review of blinded safety data by the sponsor safety review team. • Protocol-specified contraception requirements to prevent subject pregnancy. • Measures to reduce sun exposure during the treatment phase. • Prohibited medications to reduce the risk of drug interactions. • All study procedures were non-invasive, except for blood sampling and the skin biopsies taken from subjects enrolled in Cohort B. A local anaesthetic was administered before each skin biopsy. All biopsies were conducted by experienced personnel to reduce the risk of bleeding, scarring and infection.

Background therapy

Evidence for comparator

Actual start date of recruitment

12 Mar 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 56

Country: Number of subjects enrolled

United Kingdom: 12

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants with a diagnosis of moderate to severe plaque type psoriasis for at least 12 months before the first dose of study medication, who were otherwise healthy, were included in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received blinded matching placebo orally as tablets, with food, twice daily (BID), for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo tablets taken twice daily with food for up to 84 days.

GSK2586184 100 mg

Arm description

Participants received blinded 100 milligrams (mg) GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

GSK2586184

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

100 mg GSK2586184 taken twice daily with food (as tablets) for up to 84 days

GSK2586184 200 mg

Arm description

Participants received blinded 200 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

GSK2586184

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg GSK2586184 taken twice daily with food (as tablets) for up to 84 days

GSK2586184 400 mg

Arm description

Participants received blinded 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

GSK2586184

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

400 mg GSK2586184 taken twice daily with food (as tablets) for up to 84 days

GSK2586184 400 mg OL

Arm description

Participants received Open-Label 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

GSK2586184

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

400 mg GSK2586184 taken twice daily with food (as tablets) for up to 84 days

GSK2586184 200 mg OL

Arm description

Participants incorrectly received Open-Label 200 mg (rather than 400 mg) GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

GSK2586184

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg GSK2586184 taken twice daily with food (as tablets) for up to 84 days

Number of subjects in period 1 ^[1]	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Started	14	15	16	14	6	2
Completed	8	10	12	9	6	2
Not completed	6	5	4	5	0	0
Consent withdrawn by subject	2	2	-	-	-	-
Adverse event, non-fatal	2	2	2	2	-	-
Lack of efficacy	2	-	2	2	-	-
Protocol deviation	-	1	-	1	-	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Of the 68 subjects randomised, 1 subject did not receive any medication and therefore is not included in the baseline characteristic data.

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants received blinded matching placebo orally as tablets, with food, twice daily (BID), for up to 12 weeks.

Reporting group title

GSK2586184 100 mg

Reporting group description

Participants received blinded 100 milligrams (mg) GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 200 mg

Reporting group description

Participants received blinded 200 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 400 mg

Reporting group description

Participants received blinded 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 400 mg OL

Reporting group description

Participants received Open-Label 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 200 mg OL

Reporting group description

Participants incorrectly received Open-Label 200 mg (rather than 400 mg) GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL	Total
Number of subjects	14	15	16	14	6	2	67
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	49 ± 13.79	43.9 ± 14.1	49 ± 13.24	41.5 ± 12.08	50.7 ± 11.96	53.5 ± 2.12	-
Gender categorical
Units: Subjects
Female	5	6	6	8	3	2	30
Male	9	9	10	6	3	0	37
Race, Customized
Units: Subjects
African American/African Heritage	0	0	2	0	0	0	2
Asian - South East Asian Heritage	0	1	0	0	0	0	1
White - White/Caucasian/European Heritage	14	14	14	14	6	2	64

End points

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Reporting group title

Placebo

Reporting group description

Participants received blinded matching placebo orally as tablets, with food, twice daily (BID), for up to 12 weeks.

Reporting group title

GSK2586184 100 mg

Reporting group description

Participants received blinded 100 milligrams (mg) GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 200 mg

Reporting group description

Participants received blinded 200 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 400 mg

Reporting group description

Participants received blinded 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 400 mg OL

Reporting group description

Participants received Open-Label 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 200 mg OL

Reporting group description

Participants incorrectly received Open-Label 200 mg (rather than 400 mg) GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Subject analysis set title

Placebo - PP

Subject analysis set type

Per protocol

Subject analysis set description

Participants received blinded matching placebo orally as tablets, with food, twice daily (BID), for up to 12 weeks. The Per-Protocol (PP) Population included participants in the ITT analysis set who had no major protocol deviations.

Subject analysis set title

GSK2586184 100 mg - PP

Subject analysis set type

Per protocol

Subject analysis set description

Participants received blinded 100 milligrams (mg) GSK2586184 orally as tablets, with food, BID, for up to 12 weeks. The Per-Protocol (PP) Population included participants in the ITT analysis set who had no major protocol deviations.

Subject analysis set title

GSK2586184 200 mg - PP

Subject analysis set type

Per protocol

Subject analysis set description

Participants received blinded 200 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks. The Per-Protocol (PP) Population included participants in the ITT analysis set who had no major protocol deviations.

Subject analysis set title

GSK2586184 400 mg - PP

Subject analysis set type

Per protocol

Subject analysis set description

Participants received blinded 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks. The Per-Protocol (PP) Population included participants in the ITT analysis set who had no major protocol deviations.

Subject analysis set title

GSK2586184 400 mg OL - PP

Subject analysis set type

Per protocol

Subject analysis set description

Participants received Open-Label 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks. The Per-Protocol (PP) Population included participants in the ITT analysis set who had no major protocol deviations.

Primary: Percentage of participants who had achieved >=75% improvement from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 12 (PASI 75)

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End point title

Percentage of participants who had achieved >=75% improvement from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 12 (PASI 75) ^[1]

End point description

Psoriatic lesions were assessed using the PASI. Each area of the body (head, upper extremities, trunk and lower extremities) were assessed for the following symptoms: erythema, infiltration, desquamation. Baseline was Day 1. The percentage of participants who achieved a greater than or equal to (>=) 75% improvement from Baseline was reported with the last observation carried forward (LOCF) analysis. The Intent-to-Treat (ITT) Population included participants who received at least one dose of study medication.

End point type

Primary

End point timeframe

Baseline and Week 12

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 is no statistical analysis for this endpoint.

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[2]	15 ^[3]	16 ^[4]	14 ^[5]	6 ^[6]	2 ^[7]
Units: Percentage of participants
number (not applicable)	0	13	25	57	50	50

Notes
[2] - ITT Population
[3] - ITT Population
[4] - ITT Population
[5] - ITT Population
[6] - ITT Population
[7] - ITT Population

No statistical analyses for this end point

Primary: Percentage of participants who had achieved >=75% improvement from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 12 (PASI 75)

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End point title

Percentage of participants who had achieved >=75% improvement from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 12 (PASI 75) ^[8]

End point description

Psoriatic lesions were assessed using the PASI. Each area of the body (head, upper extremities, trunk and lower extremities) were assessed for the following symptoms: erythema, infiltration, desquamation. Baseline was Day 1. The percentage of participants who achieved a greater than or equal to (>=) 75% improvement from Baseline was reported with the last observation carried forward (LOCF) analysis. The Per-Protocol (PP) Population included participants in the ITT analysis set who had no major protocol deviations.

End point type

Primary

End point timeframe

Baseline and Week 12

Notes
[8] - 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 is no statistical analysis for this endpoint.

End point values	Placebo - PP	GSK2586184 100 mg - PP	GSK2586184 200 mg - PP	GSK2586184 400 mg - PP	GSK2586184 400 mg OL - PP
Number of subjects analysed	11 ^[9]	14 ^[10]	11 ^[11]	13 ^[12]	4 ^[13]
Units: Percentage of participants
number (not applicable)	0	14	36	62	75

Notes
[9] - PP Population
[10] - PP Population
[11] - PP Population
[12] - PP Population
[13] - PP Population

No statistical analyses for this end point

Secondary: Number of participants with any adverse event (AE) or serious adverse event (SAE)

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End point title

Number of participants with any adverse event (AE) or serious adverse event (SAE)

End point description

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A 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 or incapacity, or is a congenital anomaly or birth defect. Any SAEs assessed as related to study participation (e.g. study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK product was recorded from the time a participant consents to participate in the study up to and including any follow-up contact.

End point type

Secondary

End point timeframe

From the start of study up to and including the Follow-up visit (Day 112)

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[14]	15 ^[15]	16 ^[16]	14 ^[17]	6 ^[18]	2 ^[19]
Units: Participants
number (not applicable)
Any AE	13	10	14	10	6	1
Any SAE	0	2	0	1	1	0

Notes
[14] - ITT Population
[15] - ITT Population
[16] - ITT Population
[17] - ITT Population
[18] - ITT Population
[19] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with the indicated hematology parameters falling outside of the reference range at any time post-Baseline (BL) during study

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End point title

Number of participants with the indicated hematology parameters falling outside of the reference range at any time post-Baseline (BL) during study

End point description

Hematology parameters included: basophils, eosinophils, erythrocyte mean corpuscular hemoglobin (EMCHb) EMCHb concentration (EMCHbC), erythrocyte mean corpuscular volume (EMCV), erythrocyte sedimentation rate (ESR), erythrocytes, hematocrit (fraction 1), hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils, segmented neutrophils, platelets, reticulocytes. BL values were obtained at Day 1. The number of participants with the indicated hematology parameters data outside of the reference range (with high and low) any time post-BL are presented. Anytime post-BL assessments included any scheduled and unscheduled post-BL assessment. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

End point type

Secondary

End point timeframe

From BL (Day 1) until the Follow-up visit (Day 112)

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[20]	15 ^[21]	16 ^[22]	14 ^[23]	6 ^[24]	2 ^[25]
Units: Participants
number (not applicable)
Basophils, low, n=13,15,16,14,6,2	0	0	0	0	0	0
Basophils, high, n=13,15,16,14,6,2	0	0	0	0	0	0
Eosinophils, low, n=13,15,16,14,6,2	3	1	0	3	2	0
Eosinophils, high, n=13,15,16,14,6,2	0	0	0	2	0	0
EMCHbC, low, n=13,15,16,14,6,2	6	5	7	5	3	2
EMCHbC, high, n=13,15,16,14,6,2	0	0	0	0	0	0
EMCHb, low, n=13,15,16,14,6,2	0	1	1	0	0	0
EMCHb, high, n=13,15,16,14,6,2	0	1	2	2	3	0
EMCV, low, n=13,15,16,14,6,2	0	0	1	0	0	0
EMCV, high, n=13,15,16,14,6,2	0	1	3	2	3	0
ESR, low, n=0,0,2,1,2,1	0	0	0	0	0	0
ESR, high, n=0,0,2,1,2,1	0	0	1	0	0	1
Erythrocytes, low, n=13,15,16,14,6,2	0	1	2	1	0	0
Erythrocytes, high, n=13,15,16,14,6,2	1	0	0	0	0	0
Hematocrit, low, n=13,15,16,14,6,2	0	0	0	2	0	0
Hematocrit, high, n=13,15,16,14,6,2	5	1	4	0	2	0
Hemoglobin, low, n=13,15,16,14,6,2	0	2	2	0	0	1
Hemoglobin, high, n=13,15,16,14,6,2	1	1	0	1	1	0
Leukocytes, low, n=13,15,16,14,6,2	0	2	3	0	0	1
Leukocytes, high, n=13,15,16,14,6,2	3	2	4	1	1	0
Lymphocytes, low, n=13,15,16,14,6,2	0	0	4	2	0	0
Lymphocytes, high, n=13,15,16,14,6,2	0	0	2	0	0	0
Monocytes, low, n=13,15,16,14,6,2	2	1	2	3	2	0
Monocytes, high, n=13,15,16,14,6,2	1	0	1	0	0	0
Neutrophils,low, n=13,15,16,14,6,2	0	1	1	1	0	1
Neutrophils, high, n=13,15,16,14,6,2	1	2	3	2	2	0
Neutrophils, Segmented, low, n=13,15,16,14,6,2	0	1	1	1	0	1
Neutrophils, Segmented, high, n=13,15,16,14,6,2	1	2	3	2	2	0
Platelets, low, n=13,15,16,14,6,2	0	1	0	1	0	1
Platelets, high, n=13,15,16,14,6,2	1	1	1	0	0	0
Reticulocytes, low, n=13,15,16,14,6,2	3	5	5	4	0	0
Reticulocytes, high, n=13,15,16,14,6,2	2	4	3	1	3	1

Notes
[20] - ITT Population
[21] - ITT Population
[22] - ITT Population
[23] - ITT Population
[24] - ITT Population
[25] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with the indicated clinical chemistry parameters falling outside the reference range at any time post-Baseline (BL) during the study

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End point title

Number of participants with the indicated clinical chemistry parameters falling outside the reference range at any time post-Baseline (BL) during the study

End point description

Safety and tolerability were assessed by measuring the clinical chemistry parameters such as creatinine and cystatin C. BL values were obtained at Day 1. The number of participants with the indicated clinical chemistry parameter data outside of the reference range (> high or < low) at any time post-BL, including unscheduled or scheduled assessments, are presented. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X,X,X in the category titles).

End point type

Secondary

End point timeframe

From Baseline (Day 1) until the Follow-up visit (Day 112)

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[26]	15 ^[27]	16 ^[28]	14 ^[29]	6 ^[30]	2 ^[31]
Units: Participants
number (not applicable)
Creatinine, low, n=13,15,16,14,6,2	5	2	4	0	1	0
Creatinine, high, n=13,15,16,14,6,2	1	0	0	1	0	0
Cystatin C, low, n=13,15,16,14,6,2	0	0	0	2	0	1
Cystatin C, high, n=13,15,16,14,6,2	0	0	3	0	0	0

Notes
[26] - ITT Population
[27] - ITT Population
[28] - ITT Population
[29] - ITT Population
[30] - ITT Population
[31] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with the systolic (S) and diastolic (D) blood pressure (BP) falling outside the clinical concern range at any time post-baseline during the study

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End point title

Number of participants with the systolic (S) and diastolic (D) blood pressure (BP) falling outside the clinical concern range at any time post-baseline during the study

End point description

Vital sign monitoring included systolic and diastolic BP measurements. BP measurements were taken in the supine position after 5 minutes of rest. The number of participants with the SBP or DBP outside the clinical concern range at any time post-BL are presented. SBP "low" was measured as less than 85 millimeters of mercury (mmHg)and "high" was mesaured as greater than 160 mmHg. DBP "low" was measured as less than 45 mmHg and "high" was measured as greater than 100 mmHg. The BL values were those values obtained Pre-dose on Day 1. Anytime post-BL assessments included any scheduled and unscheduled post-BL assessment. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

From Baseline (Day 1) until the follow-up visit (Day 112)

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	13 ^[32]	15 ^[33]	16 ^[34]	14 ^[35]	6 ^[36]	2 ^[37]
Units: Participants
number (not applicable)
SBP, low	0	0	0	0	0	0
SBP, high	1	0	0	1	1	0
DBP, low	0	0	0	0	0	0
DBP, high	3	0	0	2	1	0

Notes
[32] - ITT Population
[33] - ITT Population
[34] - ITT Population
[35] - ITT Population
[36] - ITT Population
[37] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with the heart rate falling outside the clinical concern range at any time post-Baseline (BL) during the study

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End point title

Number of participants with the heart rate falling outside the clinical concern range at any time post-Baseline (BL) during the study

End point description

Vital sign monitoring included heart rate (HR) measurements. HR measurements were taken in supine position after 5 minutes of rest. The number of participants with HR outside the clinical concern range at any time post-BL are presented. HR "low" was any HR less than 40 beats per minute (bpm) and "high" was any HR greater than 110 bpm. The BL values were those values obtained Pre-dose on Day 1. Anytime post-BL assessments included any scheduled and unscheduled post-BL assessment.

End point type

Secondary

End point timeframe

From Baseline (Day 1) until the Follow-up visit (Day 112)

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	13 ^[38]	15 ^[39]	16 ^[40]	14 ^[41]	6 ^[42]	2 ^[43]
Units: Participants
number (not applicable)
HR, low	0	0	0	0	0	0
HR, high	0	0	0	0	0	1

Notes
[38] - ITT Population
[39] - ITT Population
[40] - ITT Population
[41] - ITT Population
[42] - ITT Population
[43] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline in body temperature

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End point title

Change from Baseline in body temperature

End point description

Vital sign monitoring included body temperature measurements. Body temperature measurements were taken in the supine position after 5 minutes of rest.The Baseline values are those values obtained Pre-dose on Day 1. Change from Baseline was determined by subtracting the indicated time point value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X,X,X in the category titles).

End point type

Secondary

End point timeframe

From Baseline (Day 1) until the Follow-up visit (Day 112)

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[44]	15 ^[45]	16 ^[46]	14 ^[47]	6 ^[48]	2 ^[49]
Units: Celsius
arithmetic mean (standard deviation)
Week 2, n=13,14,16,14,6,2	-0.2 ± 0.54	0 ± 0.38	-0.1 ± 0.73	0 ± 0.36	0 ± 0.21	0.6 ± 0.49
Week 4, n=12,14,14,13,6,2	-0.1 ± 0.52	0.1 ± 0.44	-0.1 ± 0.53	0 ± 0.28	0.3 ± 0.37	0 ± 0
Week 8, n=10,12,15,13,6,2	0.1 ± 0.44	0.1 ± 0.51	-0.2 ± 0.55	-0.1 ± 0.28	0.2 ± 0.51	0.1 ± 0.21
Week 12, n=10,10,14,10,6,2	-0.1 ± 0.38	-0.2 ± 0.64	-0.1 ± 0.38	0 ± 0.23	0 ± 0.29	0.2 ± 0
Week 16, n=8,10,12,10,6,2	0.3 ± 0.45	-0.1 ± 0.66	0.1 ± 0.39	-0.1 ± 0.21	0.4 ± 0.29	0 ± 0.35

Notes
[44] - ITT Population
[45] - ITT Population
[46] - ITT Population
[47] - ITT Population
[48] - ITT Population
[49] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with the indicated maximum change from Baseline in the electrocardiogram (ECG) findings

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End point title

Number of participants with the indicated maximum change from Baseline in the electrocardiogram (ECG) findings

End point description

ECG measurements were obtained using single 12-lead ECGs with the participant in a supine position after resting in this position for at least 10 minutes. The Baseline values were those values obtained Pre-dose on Day 1. Change from Baseline was defined as the value minus the Baseline value. The QT intervals (milliseconds [msec]) corrected for heart rate using Bazett's formula (QTcB) and Fridericia's formula (QTcF) are reported.

End point type

Secondary

End point timeframe

From Baseline (Day 1) until the Follow-up visit (Day 112)

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	13 ^[50]	15 ^[51]	16 ^[52]	14 ^[53]	6 ^[54]	2 ^[55]
Units: Participants
number (not applicable)
QTcB, <30 msec	13	14	16	12	6	2
QTcB, >=30 to <60 msec	0	1	0	2	0	0
QTcB, >60 msec	0	0	0	0	0	0
QTcF, <30 msec	13	15	16	12	6	2
QTcF, >=30 to <60 msec	0	0	0	2	0	0
QTcF, >60 msec	0	0	0	0	0	0

Notes
[50] - ITT Population
[51] - ITT Population
[52] - ITT Population
[53] - ITT Population
[54] - ITT Population
[55] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline (BL) in the PASI score at Week 2, 4, 8 and 12

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End point title

Change from Baseline (BL) in the PASI score at Week 2, 4, 8 and 12

End point description

Psoriatic lesions were assessed using the PASI. Each area of the body (head, upper extremities, trunk and lower extremities) were assessed for the following symptoms: erythema, infiltration, desquamation. Baseline was Day 1. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X,X,X in the category titles).

End point type

Secondary

End point timeframe

From Baseline (Day 1) until Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[56]	15 ^[57]	16 ^[58]	14 ^[59]	6 ^[60]	2 ^[61]
Units: PASI score
arithmetic mean (standard deviation)
Week 2,n=13,14,16,14,6,2	-0.05 ± 1.716	-2.39 ± 3.12	-0.51 ± 7.693	-3.94 ± 4.766	-5.25 ± 4.192	-3.75 ± 2.192
Week 4, n=12,14,14,13,6,2	-0.73 ± 3.335	-4.5 ± 4.344	-7.03 ± 7.594	-8.04 ± 7.739	-9.1 ± 3.854	-8.2 ± 0.99
Week 8, n=10, 12,15,13,6,2	-1.41 ± 2.122	-6.54 ± 6.915	-8.45 ± 11.396	-10.32 ± 8.293	-7.85 ± 5.39	-11.5 ± 0.424
Week 12, n=10,10,14,10,6,2	-3.13 ± 2.694	-9.76 ± 6.341	-9.21 ± 12.446	-13.55 ± 6.393	-9.37 ± 7.181	-12.45 ± 1.061

Notes
[56] - ITT Population
[57] - ITT Population
[58] - ITT Population
[59] - ITT Population
[60] - ITT Population
[61] - ITT Population

No statistical analyses for this end point

Secondary: PASI score at Week 2, 4, 8 and 12

Top of page

End point title

PASI score at Week 2, 4, 8 and 12

End point description

Psoriatic lesions were assessed using the PASI. Each area of the body (head, upper extremities, trunk and lower extremities) were assessed for the following symptoms: erythema, infiltration, desquamation. Baseline was Day 1. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X,X,X in the category titles).

End point type

Secondary

End point timeframe

Week 2, 4, 8 and 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[62]	15 ^[63]	16 ^[64]	14 ^[65]	6 ^[66]	2 ^[67]
Units: PASI score
arithmetic mean (standard deviation)
Week 2,n=13,14,16,14,6,2	16.33 ± 4.896	16.56 ± 5.708	18.92 ± 9.969	13.39 ± 5.594	13.75 ± 4.807	11.2 ± 0.283
Week 4, n=12,14,14,13,6,2	15.12 ± 4.683	13.94 ± 6.616	12.59 ± 5.524	9.58 ± 7.91	9.9 ± 6.271	6.75 ± 1.485
Week 8, n=10, 12,15,13,6,2	14.64 ± 4.289	12.56 ± 5.442	11.03 ± 8.322	7.3 ± 9.11	11.15 ± 9.573	3.45 ± 2.899
Week 12, n=10,10,14,10,6,2	12.92 ± 3.384	10.52 ± 4.932	9.67 ± 7.799	4.03 ± 4.666	9.63 ± 10.688	2.5 ± 3.536

Notes
[62] - ITT Population
[63] - ITT Population
[64] - ITT Population
[65] - ITT Population
[66] - ITT Population
[67] - ITT Population

No statistical analyses for this end point

Secondary: Percentage of participants who had a PASI score with 50%, 75% and 90% improvement from Baseline (BL) until Week 12

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End point title

Percentage of participants who had a PASI score with 50%, 75% and 90% improvement from Baseline (BL) until Week 12

End point description

Psoriatic lesions were assessed using the PASI. Each area of the body (head, upper extremities, trunk and lower extremities) were assessed for the following symptoms: erythema, infiltration, desquamation. Baseline was Day 1. The percentage of participants who achieved greater than or equal to (>=) 50% (PASI 50) improvement from baseline, >= 75% (PASI 75) improvement from BL and >= to 90% (PASI 90) improvement from BL were reported with the last observation carried forward (LOCF) analysis.

End point type

Secondary

End point timeframe

From Baseline (Day 1) until Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[68]	15 ^[69]	16 ^[70]	14 ^[71]	6 ^[72]	2 ^[73]
Units: Percentage of Participants
number (not applicable)
PASI 50, Week 2	0	7	6	7	17	0
PASI 50, Week 4	0	13	25	57	50	100
PASI 50, Week 8	0	20	31	71	50	100
PASI 50, Week 12	0	27	31	64	50	100
PASI 75, Week 2	0	0	0	0	0	0
PASI 75, Week 4	0	7	6	21	0	0
PASI 75, Week 8	0	7	25	50	17	50
PASI 90, Week 2	0	0	0	0	0	0
PASI 90, Week 4	0	0	0	0	0	0
PASI 90, Week 8	0	7	6	14	0	0
PASI 90, Week 12	0	0	25	36	17	50

Notes
[68] - ITT Population
[69] - ITT Population
[70] - ITT Population
[71] - ITT Population
[72] - ITT Population
[73] - ITT Population

No statistical analyses for this end point

Secondary: Percentage of participants who had a Physician Global Assessment (PGA) score of ‘clear’ (0) or ‘almost clear’ (1) at Weeks 2, 4, 8 and 12

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End point title

Percentage of participants who had a Physician Global Assessment (PGA) score of ‘clear’ (0) or ‘almost clear’ (1) at Weeks 2, 4, 8 and 12

End point description

The severity of psoriatic lesions over the whole body were assessed by the investigator using the PGA scoring system. A 0 to 6 point rating scale was used, as follows: 0 = Clear (no signs of psoriasis), 1 = Almost clear (slight elevation, scale and/or erythema), 2 = Mild (mild plaque elevation, scale and/or erythema), 3 = Mild to moderate (mild plaque elevation with moderate erythema and/or scale)4 = Moderate (moderate plaque elevation, scale and/or erythema), 5 = Moderate to severe (marked plaque elevation, scale and/or erythema), 6 = Severe (very marked plaque elevation, scale and/or erythema). The Baseline value was the value obtained on Day 1. The scores were reported with the last observation carried forward (LOCF) analysis.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8 and 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[74]	15 ^[75]	16 ^[76]	14 ^[77]	6 ^[78]	2 ^[79]
Units: Percentage of Participants
number (not applicable)
Week 2	0	0	6	0	0	0
Week 4	0	0	6	0	0	0
Week 8	0	7	6	29	0	50
Week 12	0	7	25	43	17	50

Notes
[74] - ITT Population
[75] - ITT Population
[76] - ITT Population
[77] - ITT Population
[78] - ITT Population
[79] - ITT Population

No statistical analyses for this end point

Secondary: Percentage of participants in each PGA score category at Weeks 2, 4, 8 and 12

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End point title

Percentage of participants in each PGA score category at Weeks 2, 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Weeks 2, 4, 8 and 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[80]	15 ^[81]	16 ^[82]	14 ^[83]	6 ^[84]	2 ^[85]
Units: Percentage of Participants
number (not applicable)
Week 2, Clear, n=13,14,16,14,6,2	0	0	0	0	0	0
Week 2, almost clear, n=13,14,16,14,6,2	0	0	6	0	0	0
Week 2, mild, n=13,14,16,14,6,2	0	0	0	0	0	0
Week 2, mild to moderate, n=13,14,16,14,6,2	23	14	19	43	33	0
Week 2, moderate, n=13,14,16,14,6,2	46	64	44	36	50	50
Week 2, moderate to severe, n=13,14,16,14,6,2	31	14	13	14	0	50
Week 2, severe, n=13,14,16,14,6,2	0	7	19	7	17	0
Week 4, Clear, n=12,14,14,13,6,2	0	0	0	0	0	0
Week 4, almost clear, n=12,14,14,13,6,2	0	0	7	0	0	0
Week 4, mild, n=12,14,14,13,6,2	0	14	0	23	33	0
Week 4, mild to moderate, n=12,14,14,13,6,2	25	36	29	54	33	0
Week 4, moderate, n=12,14,14,13,6,2	50	29	43	8	17	100
Week 4, moderate to severe, n=12,14,14,13,6,2	25	14	14	15	17	0
Week 4, severe, n=12,14,14,13,6,2	0	7	7	0	0	0
Week 8, Clear, n=10,11,15,13,6,2	0	0	0	0	0	0
Week 8, almost clear, n=10,11,15,13,6,2	0	9	7	31	0	50
Week 8, mild, n=10,11,15,13,6,2	0	9	20	23	50	0
Week 8, mild to moderate, n=10,11,15,13,6,2	22	27	20	23	17	50
Week 8, moderate, n=10,11,15,13,6,2	44	36	33	8	0	0
Week 8, moderate to severe, n=10,11,15,13,6,2	33	9	13	8	33	0
Week 8, severe, n=10,11,15,13,6,2	0	9	7	8	0	0
Week 12, Clear, n=10,10,14,10,6,2	0	0	7	30	0	50
Week 12, almost clear, n=10,10,14,10,6,2	0	10	21	20	17	0
Week 12, mild, n=10,10,14,10,6,2	10	0	0	20	17	0
Week 12, mild to moderate, n=10,10,14,10,6,2	30	50	29	20	33	50
Week 12, moderate, n=10,10,14,10,6,2	50	30	21	0	17	0
Week 12, moderate to severe, n=10,10,14,10,6,2	10	10	21	0	17	0
Week 12, Severe, n=10,10,14,10,6,2	0	0	0	10	0	0

Notes
[80] - ITT Population
[81] - ITT Population
[82] - ITT Population
[83] - ITT Population
[84] - ITT Population
[85] - ITT Population

No statistical analyses for this end point

Secondary: Time to PASI 75

Top of page

End point title

Time to PASI 75

End point description

The time taken for participants to achieve PASI 75. Psoriatic lesions were assessed using the PASI. Each area of the body (head, upper extremities, trunk and lower extremities) were assessed for the following symptoms: erythema, infiltration, desquamation. Baseline was Day 1. The time (Days) for participants to achieve a greater than or equal to (>=) 75% improvement from Baseline was reported.

End point type

Secondary

End point timeframe

From Baseline (Day 1) until Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	0 ^[86]	2 ^[87]	4 ^[88]	9 ^[89]	3 ^[90]	1 ^[91]
Units: Days
median (full range (min-max))	( to )	59 (33 to 85)	55.5 (29 to 63)	57 (27 to 85)	84 (56 to 85)	57 (57 to 57)

Notes
[86] - ITT Population
[87] - ITT Population
[88] - ITT Population
[89] - ITT Population
[90] - ITT Population
[91] - ITT Population

No statistical analyses for this end point

Secondary: Time to PGA score of 'clear' (0) or 'almost clear' (1)

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End point title

Time to PGA score of 'clear' (0) or 'almost clear' (1)

End point description

End point type

Secondary

End point timeframe

From Baseline (Day 1) until Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	0 ^[92]	1 ^[93]	4 ^[94]	6 ^[95]	1 ^[96]	1 ^[97]
Units: Days
median (full range (min-max))	( to )	55 (55 to 55)	84.5 (15 to 85)	57 (55 to 87)	84 (84 to 84)	57 (57 to 57)

Notes
[92] - ITT Population
[93] - ITT Population
[94] - ITT Population
[95] - ITT Population
[96] - ITT Population
[97] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline in the itch visual analogue scale (VAS) score at Week 2, 4, 8 and 12

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End point title

Change from Baseline in the itch visual analogue scale (VAS) score at Week 2, 4, 8 and 12

End point description

Participants rated the intensity of itch over the past week by marking a line on the VAS, a 10 centimeter (cm) long scale. A line placed on the left indicated no noticeable itching sensation and a line placed on the right indicated maximum itching sensation). The Baseline value was the value obtained on Day 1. The change from Baseline was the difference between post-Baseline and Baseline. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X,X,X in the category titles).

End point type

Secondary

End point timeframe

From Baseline (Day 1) until Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[98]	15 ^[99]	16 ^[100]	14 ^[101]	6 ^[102]	2 ^[103]
Units: Change from baseline
arithmetic mean (standard deviation)
Week 2,n=12,14,15,12,6,2	-5.67 ± 32.129	-14.79 ± 31.396	-14.87 ± 23.67	-24.92 ± 24.737	-56.33 ± 30.329	-22 ± 43.841
Week 4,n=10,12,14,12,6,2	-7 ± 37.944	-26.5 ± 28.659	-22.36 ± 27.244	-28.08 ± 25.678	-47.5 ± 39.48	-30 ± 62.225
Week 8,n=9,11,14,10,6,2	0.22 ± 26.138	-26.27 ± 35.707	-24.86 ± 37.134	-36.3 ± 29.788	-61.5 ± 31.729	-32.5 ± 65.761
Week 12,n=9,10,13,8,5,2	-1.56 ± 34.348	-21.4 ± 40.533	-23.92 ± 40.586	-41.13 ± 31.791	-60.8 ± 38.16	-25 ± 76.368

Notes
[98] - ITT Population
[99] - ITT Population
[100] - ITT Population
[101] - ITT Population
[102] - ITT Population
[103] - ITT Population

No statistical analyses for this end point

Secondary: Itch VAS scores at Week 2, 4, 8 and 12

Top of page

End point title

Itch VAS scores at Week 2, 4, 8 and 12

End point description

Participants rated the intensity of itch over the past week by marking a line on the VAS, a 10 cm long scale. A line placed on the left indicated no noticeable itching sensation and a line placed on the right indicated maximum itching sensation). Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X,X,X in the category titles).

End point type

Secondary

End point timeframe

Week 2, 4, 8 and 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[104]	15 ^[105]	16 ^[106]	14 ^[107]	6 ^[108]	2 ^[109]
Units: VAS scores
arithmetic mean (standard deviation)
Week 2,n=12,14,15,12,6,2	46.42 ± 28.909	41.64 ± 21.995	42.07 ± 31.176	22.92 ± 21.707	11.83 ± 14.73	42 ± 22.627
Week 4,n=10,12,14,13,6,2	44.4 ± 35.485	33.42 ± 25.939	32.57 ± 30.729	23.85 ± 23.14	20.67 ± 30.051	34 ± 41.012
Week 8,n=9,11,14,11,6,2	57.33 ± 29.368	31.55 ± 29.156	29.93 ± 29.437	14.45 ± 21.92	6.67 ± 7.763	31.5 ± 44.548
Week 12,n=9,10,13,9,5,2	50.67 ± 37.683	39.5 ± 33.58	30.08 ± 34.697	14 ± 23.701	5.4 ± 6.693	39 ± 55.154

Notes
[104] - ITT Population
[105] - ITT Population
[106] - ITT Population
[107] - ITT Population
[108] - ITT Population
[109] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline of Dermatology Life Quality Index (DLQI) score at Week 12

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End point title

Change from Baseline of Dermatology Life Quality Index (DLQI) score at Week 12

End point description

The DLQI was used to assess quality of life. Participants completed the questionnaire to evaluate how their psoriasis affected their life over the week before the assessment took place. Each of the 10 questions was scored out of 0–3 as; 0 = Not at all, 1 = A little, 2 = A lot and 3 = Very much. The Baseline value was the value obtained on Day 1. The change from Baseline was the difference between post- Baseline and Baseline. Only those participants who had a Week 12 evaluation were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	10 ^[110]	10 ^[111]	14 ^[112]	10 ^[113]	4 ^[114]	2 ^[115]
Units: Change from baseline
arithmetic mean (standard deviation)	1.7 ± 5.638	-2.8 ± 7.743	-4.29 ± 8.389	-8 ± 3.83	-6.75 ± 5.123	-8 ± 11.314

Notes
[110] - ITT Population
[111] - ITT Population
[112] - ITT Population
[113] - ITT Population
[114] - ITT Population
[115] - ITT Population

No statistical analyses for this end point

Secondary: Population pharmacokinetic (PK) derived area under the concentration-time curve from time zero (pre-dose) to the time of the last measureable concentration AUC(0-tau) of GSK2586184

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End point title

Population pharmacokinetic (PK) derived area under the concentration-time curve from time zero (pre-dose) to the time of the last measureable concentration AUC(0-tau) of GSK2586184

End point description

Blood samples were taken to measure plasma concentrations of GSK2586184. A two-compartment model with a three-compartment transit model was used to derive PK parameters. The PK Population comprised of all participants who were randomized and received at least one dose of study medication.

End point type

Secondary

End point timeframe

From Baseline (Day 1) until Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	0 ^[116]	15 ^[117]	15 ^[118]	14 ^[119]	6 ^[120]	2 ^[121]
Units: Nanogram/milliLitrehour (ng/mLhr)
geometric mean (geometric coefficient of variation)	±	1464.079 ± 43.9	3516.962 ± 38.7	7768.408 ± 62.4	7561.88 ± 79.1	3208.205 ± 53.5

Notes
[116] - PK Population
[117] - PK Population
[118] - PK Population
[119] - PK Population
[120] - PK Population
[121] - PK Population

No statistical analyses for this end point

Secondary: Clearance of GSK2586184

Top of page

End point title

Clearance of GSK2586184

End point description

End point type

Secondary

End point timeframe

From Baseline (Day 1) until Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	0 ^[122]	15 ^[123]	15 ^[124]	14 ^[125]	6 ^[126]	2 ^[127]
Units: Litre (L)/hr
geometric mean (geometric coefficient of variation)	±	68.30232 ± 43.9	56.86726 ± 38.7	51.4906 ± 62.4	52.8969 ± 79.1	62.34017 ± 53.5

Notes
[122] - PK Population
[123] - PK Population
[124] - PK Population
[125] - PK Population
[126] - PK Population
[127] - PK Population

No statistical analyses for this end point

Secondary: Steady state volume of distribution (Vss) of GSK2586184

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End point title

Steady state volume of distribution (Vss) of GSK2586184

End point description

End point type

Secondary

End point timeframe

From Baseline (Day 1) until Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	0 ^[128]	15 ^[129]	15 ^[130]	14 ^[131]	6 ^[132]	2 ^[133]
Units: Liters (L)
geometric mean (geometric coefficient of variation)	±	244.1026 ± 62.3	193.7534 ± 47.1	186.7832 ± 64.4	199.7375 ± 85.4	216.0036 ± 66.5

Notes
[128] - PK Population
[129] - PK Population
[130] - PK Population
[131] - PK Population
[132] - PK Population
[133] - PK Population

No statistical analyses for this end point

Secondary: Change from baseline in serum neopterin concentrations at Weeks 2, 4, 8 and 12

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End point title

Change from baseline in serum neopterin concentrations at Weeks 2, 4, 8 and 12

End point description

Serum Neopterin is a marker of psoriatic disease activity. Blood samples were collected for estimation of serum neoprotein concentration. Baseline was Day 1.

End point type

Secondary

End point timeframe

From Baseline (Day 1) until Week 12

End point values	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Number of subjects analysed	14 ^[134]	15 ^[135]	16 ^[136]	14 ^[137]	6 ^[138]	2 ^[139]
Units: Change from baseline (nmol/L)
arithmetic mean (standard deviation)
Week 2,n=13,14,14,12,6,2	0.19 ± 1.219	0.43 ± 5.394	2.35 ± 6.475	-0.42 ± 1.858	-0.47 ± 0.918	9.95 ± 13.93
Week 4, n=10,14,13,10,6,2	0.18 ± 0.844	-1.69 ± 2.933	-1.15 ± 1.768	-0.69 ± 1.195	-0.67 ± 0.378	1.8 ± 2.828
Week 8, n=10,12,15,11,5,2	-0.14 ± 0.597	-1.13 ± 2.312	-0.81 ± 2.294	0.31 ± 2.998	-0.4 ± 1.52	0.15 ± 2.192
Week 12, n= 8,9,14,9,6,2	-0.01 ± 1.038	-1.32 ± 2.355	-0.79 ± 1.738	4.37 ± 13.387	-0.42 ± 1.182	0.35 ± 0.212

Notes
[134] - ITT Population
[135] - ITT Population
[136] - ITT Population
[137] - ITT Population
[138] - ITT Population
[139] - ITT Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Non-serious Adverse Events (AEs) were collected from the start of study treatment up to and including the Follow-up visit (up to Study Week 16), Serious AEs were recorded from the time of consent to treatment up to and including the Follow-up visit.

Adverse event reporting additional description

SAEs and non-serious AEs are reported for the Intent-to-Treat Population, comprised of all participants who received at least one dose of study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Placebo

Reporting group description

Participants received blinded matching placebo orally as tablets, with food, twice daily (BID), for up to 12 weeks.

Reporting group title

GSK2586184 100 mg

Reporting group description

Participants received blinded 100 milligrams (mg) GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 200 mg

Reporting group description

Participants received blinded 200 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 400 mg

Reporting group description

Participants received blinded 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 400 mg OL

Reporting group description

Participants received Open-Label 400 mg GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Reporting group title

GSK2586184 200 mg OL

Reporting group description

Participants incorrectly received Open-Label 200 mg (rather than 400 mg) GSK2586184 orally as tablets, with food, BID, for up to 12 weeks.

Serious adverse events	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 16 (0.00%)	1 / 14 (7.14%)	1 / 6 (16.67%)	0 / 2 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Ligament rupture
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Calculus ureteric
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	GSK2586184 100 mg	GSK2586184 200 mg	GSK2586184 400 mg	GSK2586184 400 mg OL	GSK2586184 200 mg OL
Total subjects affected by non serious adverse events
subjects affected / exposed	13 / 14 (92.86%)	10 / 15 (66.67%)	14 / 16 (87.50%)	10 / 14 (71.43%)	6 / 6 (100.00%)	1 / 2 (50.00%)
Vascular disorders
Hypertension
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	2	0
Hot flush
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	7	0	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 14 (7.14%)	3 / 15 (20.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	4	0	1	0	0
Pyrexia
subjects affected / exposed	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	2	0	0	0	2
Chills
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0	0	0
Feeling hot
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	2	0	0	0
Psychiatric disorders
Nightmare
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Investigations
Blood cholesterol increased
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	2 / 16 (12.50%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	2	0	0	0
Blood triglycerides increased
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	1	0	0	0
Alanine aminotransferase increased
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	0	0	1	0
Low density lipoprotein increased
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Injury, poisoning and procedural complications
Limb injury
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Lip injury
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Post procedural complication
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	0	0
Road traffic accident
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	0	0
Skin injury
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0	0	0
Cardiac disorders
Tachycardia
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	1	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	5 / 14 (35.71%)	5 / 15 (33.33%)	3 / 16 (18.75%)	3 / 14 (21.43%)	2 / 6 (33.33%)	1 / 2 (50.00%)
occurrences all number	9	5	5	4	6	1
Dizziness
subjects affected / exposed	0 / 14 (0.00%)	3 / 15 (20.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	3	0	1	0	0
Burning sensation
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Migraine
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Somnolence
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	2	0	0	0	0	0
Eye disorders
Visual impairment
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 14 (14.29%)	1 / 15 (6.67%)	0 / 16 (0.00%)	2 / 14 (14.29%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	2	1	0	3	3	0
Abdominal pain upper
subjects affected / exposed	1 / 14 (7.14%)	1 / 15 (6.67%)	2 / 16 (12.50%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	1	1	2	0	1	0
Diarrhoea
subjects affected / exposed	2 / 14 (14.29%)	2 / 15 (13.33%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	3	2	0	2	0	0
Abdominal pain
subjects affected / exposed	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0	0	0
Abdominal distension
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Constipation
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Dyspepsia
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	0	0
Eructation
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	0	0
Food poisoning
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Inguinal hernia
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Tongue coated
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	0	0	1	0
Toothache
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Vomiting
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	2	0	0
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	2 / 14 (14.29%)	2 / 15 (13.33%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	3	2	0	0	0	0
Psoriasis
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	3 / 16 (18.75%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	3	0	1	0
Pruritus generalised
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	1	0
Acne
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Cold sweat
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0	0	0
Eczema
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Guttate psoriasis
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	0	0	1	0
Rash papular
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0	0	0
Skin fissures
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 14 (7.14%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	1	0	0	0	0
Back pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	0	1	0	2
Arthritis
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	0	0	0	3
Growing pains
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	0	0	0	1
Muscle spasms
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	3	0	0	0
Muscle tightness
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Pain in extremity
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Psoriatic arthropathy
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	0	0	0	2
Infections and infestations
Nasopharyngitis
subjects affected / exposed	3 / 14 (21.43%)	5 / 15 (33.33%)	4 / 16 (25.00%)	5 / 14 (35.71%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	3	7	4	7	1	0
Cystitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	1	0	0
Influenza
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	1	0	0
Abscess limb
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	0	0	1	0
Acne pustular
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Bacterial disease carrier
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	0	0	1	0
Enterobiasis
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Gastrointestinal viral infection
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	0	0	1	0
Gingivitis
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	0	1	0	0
Post procedural infection
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0	0	0
Tinea pedis
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	0	0
Tooth abscess
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0	0	0
Urinary tract infection
subjects affected / exposed	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0	0	0
Metabolism and nutrition disorders
Hypertriglyceridaemia
subjects affected / exposed	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0	0	0
Vitamin B12 deficiency
subjects affected / exposed	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	0	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

06 Mar 2013

(Germany only) To further clarify the dermatological withdrawal criteria, in response to a request by the Ethics Committee in Germany.

09 Jul 2013

To update the relevant sections of the protocol following the release of new monkey toxicology data.

30 Oct 2013

To revise the contraception requirements for male subjects with female partners of reproductive potential, and revise reporting and follow up requirements for pregnancies in female partners of male subjects, following a safety evaluation review.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A multi-centre, randomised, double-blind, placebo-controlled, dose ranging study to evaluate the safety and efficacy of GSK2586184 in patients with chronic plaque psoriasis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants who had achieved >=75% improvement from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 12 (PASI 75)

Primary: Percentage of participants who had achieved >=75% improvement from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 12 (PASI 75)

Primary: Percentage of participants who had achieved >=75% improvement from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 12 (PASI 75)

Primary: Percentage of participants who had achieved >=75% improvement from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 12 (PASI 75)

Secondary: Number of participants with any adverse event (AE) or serious adverse event (SAE)

Secondary: Number of participants with any adverse event (AE) or serious adverse event (SAE)

Secondary: Number of participants with the indicated hematology parameters falling outside of the reference range at any time post-Baseline (BL) during study

Secondary: Number of participants with the indicated hematology parameters falling outside of the reference range at any time post-Baseline (BL) during study

Secondary: Number of participants with the indicated clinical chemistry parameters falling outside the reference range at any time post-Baseline (BL) during the study

Secondary: Number of participants with the indicated clinical chemistry parameters falling outside the reference range at any time post-Baseline (BL) during the study

Secondary: Number of participants with the systolic (S) and diastolic (D) blood pressure (BP) falling outside the clinical concern range at any time post-baseline during the study

Secondary: Number of participants with the systolic (S) and diastolic (D) blood pressure (BP) falling outside the clinical concern range at any time post-baseline during the study

Secondary: Number of participants with the heart rate falling outside the clinical concern range at any time post-Baseline (BL) during the study

Secondary: Number of participants with the heart rate falling outside the clinical concern range at any time post-Baseline (BL) during the study

Secondary: Change from Baseline in body temperature

Secondary: Change from Baseline in body temperature

Secondary: Number of participants with the indicated maximum change from Baseline in the electrocardiogram (ECG) findings

Secondary: Number of participants with the indicated maximum change from Baseline in the electrocardiogram (ECG) findings

Secondary: Change from Baseline (BL) in the PASI score at Week 2, 4, 8 and 12

Secondary: Change from Baseline (BL) in the PASI score at Week 2, 4, 8 and 12

Secondary: PASI score at Week 2, 4, 8 and 12

Secondary: PASI score at Week 2, 4, 8 and 12

Secondary: Percentage of participants who had a PASI score with 50%, 75% and 90% improvement from Baseline (BL) until Week 12

Secondary: Percentage of participants who had a PASI score with 50%, 75% and 90% improvement from Baseline (BL) until Week 12

Secondary: Percentage of participants who had a Physician Global Assessment (PGA) score of ‘clear’ (0) or ‘almost clear’ (1) at Weeks 2, 4, 8 and 12

Secondary: Percentage of participants who had a Physician Global Assessment (PGA) score of ‘clear’ (0) or ‘almost clear’ (1) at Weeks 2, 4, 8 and 12

Secondary: Percentage of participants in each PGA score category at Weeks 2, 4, 8 and 12

Secondary: Percentage of participants in each PGA score category at Weeks 2, 4, 8 and 12

Secondary: Time to PASI 75

Secondary: Time to PASI 75

Secondary: Time to PGA score of 'clear' (0) or 'almost clear' (1)

Secondary: Time to PGA score of 'clear' (0) or 'almost clear' (1)

Secondary: Change from Baseline in the itch visual analogue scale (VAS) score at Week 2, 4, 8 and 12

Secondary: Change from Baseline in the itch visual analogue scale (VAS) score at Week 2, 4, 8 and 12

Secondary: Itch VAS scores at Week 2, 4, 8 and 12

Secondary: Itch VAS scores at Week 2, 4, 8 and 12

Secondary: Change from Baseline of Dermatology Life Quality Index (DLQI) score at Week 12

Secondary: Change from Baseline of Dermatology Life Quality Index (DLQI) score at Week 12

Secondary: Population pharmacokinetic (PK) derived area under the concentration-time curve from time zero (pre-dose) to the time of the last measureable concentration AUC(0-tau) of GSK2586184

Secondary: Population pharmacokinetic (PK) derived area under the concentration-time curve from time zero (pre-dose) to the time of the last measureable concentration AUC(0-tau) of GSK2586184

Secondary: Clearance of GSK2586184

Secondary: Clearance of GSK2586184

Secondary: Steady state volume of distribution (Vss) of GSK2586184

Secondary: Steady state volume of distribution (Vss) of GSK2586184

Secondary: Change from baseline in serum neopterin concentrations at Weeks 2, 4, 8 and 12

Secondary: Change from baseline in serum neopterin concentrations at Weeks 2, 4, 8 and 12

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A multi-centre, randomised, double-blind, placebo-controlled, dose ranging study to evaluate the safety and efficacy of GSK2586184 in patients with chronic plaque psoriasis